Abstract

Mesenchymal stem cells (MSCs) encapsulation by three-dimensionally (3D) printed matrices were believed to provide a biomimetic microenvironment to drive differentiation into tissue-specific progeny, which made them a great therapeutic potential for regenerative medicine. Despite this potential, the underlying mechanisms of controlling cell fate in 3D microenvironments remained relatively unexplored. Here, we bioprinted a sweat gland (SG)like matrix to direct the conversion of MSC into functional SGs and facilitated SGs recovery in mice. By extracellular matrix differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator for SG specification. Our findings showed that Hmox1 could respond to the 3D structure activation and also be involved in MSC differentiation. Using inhibition and activation assay, CTHRC1 and Hmox1 synergistically boosted SG gene expression profile. Together, these findings indicated that biochemical and structural cues served as two critical impacts of 3D-printed matrix on MSC fate decision into the glandular lineage and functional SG recovery.

Mesenchymal stem cells (MSCs) hold great promise for therapeutic tissue engineering and regenerative medicine, largely because of their capacity for self-renewal and multipotent properties (1). However, their uncertain fate has a major impact on their envisioned therapeutic use. Cell fate regulation requires specific transcription programs in response to environmental cues (2, 3). Once stem cells are removed from their microenvironment, their response to environmental cues, phenotype, and functionality could often be altered (4, 5). In contrast to growing information concerning transcriptional regulation, guidance from the extracellular matrix (ECM) governing MSC identity and fate determination is not well understood. It remains an active area of investigation and may provide previously unidentified avenues for MSC-based therapy.

Over the past decade, engineering three-dimensional (3D) ECM to direct MSC differentiation has demonstrated great potential of MSCs in regenerative medicine (6). 3D ECM has been found to be useful in providing both biochemical and biophysical cues and to stabilize newly formed tissues (7). Culturing cells in 3D ECM radically alters the interfacial interactions with the ECM as compared with 2D ECM, where cells are flattened and may lose their differentiated phenotype (8). However, one limitation of 3D materials as compared to 2D approaches was the lack of spatial control over chemistry with 3D materials. One possible solution to this limitation is 3D bioprinting, which could be used to design the custom scaffolds and tissues (9).

In contrast to traditional engineering techniques, 3D cell printing technology is especially advantageous because it can integrate multiple biophysical and biochemical cues spatially for cellular regulation and ensure complex structures with precise control and high reproducibility. In particular, for our final goal of clinical practice, extrusion-based bioprinting may be more appropriate for translational application. In addition, as a widely used bioink for extrusion bioprinting, alginate-based hydrogel could maintain stemness of MSC due to the bioinert property and improve biological activity and printability by combining gelatin (10).

Sweat glands (SGs) play a vital role in thermal regulation, and absent or malfunctioning SGs in a hot environment can lead to hyperthermia, stroke, and even death in mammals (11, 12). Each SG is a single tube consisting of a functionally distinctive duct and secretory portions. It has low regenerative potential in response to deep dermal injury, which poses a challenge for restitution of lost cells after wound (13). A major obstacle in SG regeneration, similar to the regeneration of most other glandular tissues, is the paucity of viable cells capable of regenerating multiple tissue phenotypes (12). Several reports have described SG regeneration in vitro; however, dynamic morphogenesis was not identified nor was the overall function of the formed tissues explored (1416). Recent advances in bioprinting and tissue engineering led to the complexities in the matrix design and fabrication with appropriate biochemical cues and biophysical guidance for SG regeneration (1719).

Here, we adopted 3D bioprinting technique to mimic the regenerative microenvironment that directed the specific SG differentiation of MSCs and ultimately guided the formation and function of glandular tissue. We used alginate/gelatin hydrogel as bioinks in this present study due to its good cytocompatibility, printability, and structural maintenance in long-time culture. Although the profound effects of ECM on cell differentiation was well recognized, the importance of biochemical and structural cues of 3D-printed matrix that determined the cell fate of MSCs remained unknown; thus, the present study demonstrated the role of 3D-printed matrix cues on cellular behavior and tissue morphogenesis and might help in developing strategies for MSC-based tissue regeneration or directing stem cell lineage specification by 3D bioprinting.

The procedure for printing the 3D MSC-loaded construct incorporating a specific SG ECM (mouse plantar region dermis, PD) was shown schematically in Fig. 1A. A 3D cellular construct with cross section 30 mm 30 mm and height of 3 mm was fabricated by using the optimized process parameter (20). The 3D construct demonstrated a macroporous grid structure with hydrogel fibers evenly distributed according to the computer design. Both the width of the fibers and the gap between the fibers were homogeneous, and MSCs were embedded uniformly in the hydrogel matrix fibers to result in a specific 3D microenvironment. (Fig. 1B).

(A) Schematic description of the approach. (B) Full view of the cellular construct and representative microscopic and fluorescent images and the quantitative parameters of 3D-printed construct (scale bars, 200 m). Photo credit: Bin Yao, Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Sciences, General Hospital of PLA. (C) Representative microscopy images of cell aggregates and tissue morphology at 3, 7, and 14 days of culture (scale bars, 50 m) and scanning electron microscopy (sem) images of 3D structure (scale bars, 20 m). PD+/PD, 3D construct with and without PD. (D) DNA contents, collagen, and GAGs of native tissue and PD. (E) Proliferating cells were detected through Ki67 stain at 3, 7, and 14 days of culture. (F) Live/dead assay show cell viability at days 3, 7, and 14. *P < 0.05.

During the maintenance of constructs for stem cell expansion, MSCs proliferated to form aggregates of cells but self-assembled to an SG-like structure only with PD administration (Fig. 1C and fig. S1, A to C). We carried out DNA quantification assay to evaluate the cellular content in PD and found the cellular matrix with up to 90% reduction, only 3.4 0.7 ng of DNA per milligram tissue remaining in the ECM. We also estimated the proportions of collagen and glycosaminoglycans (GAGs) in ECM through hydroxyproline assay and dimethylmethylene blue assay, the collagen contents could increase to 112.6 11.3%, and GAGs were well retained to 81 9.6% (Fig. 1D). Encapsulated cells were viable, with negligible cell death apparent during extrusion and ink gelation by ionic cross-linking, persisting through extended culture in excess of 14 days. The fluorescence intensity of Ki67 of MSCs cultured in 2D condition decreased from days 3 (152.7 13.4) to 14 (29.4 12.9), while maintaining higher intensity of MSCs in 3D construct (such as 211.8 19.4 of PD+3D group and 209.1 22.1 of PD3D group at day 14). And the cell viability in 3D construct was found to be sufficiently high (>80%) when examined on days 3, 7, and 14. The phenomenon of cell aggregate formation and increased cell proliferation implied the excellent cell compatibility of the hydrogel-based construct and promotion of tissue development of 3D architectural guides, which did not depend on the presence or absence of PD (Fig. 1, E and F).

The capability of 3D-printed construct with PD directing MSC to SGs in vitro was investigated. The 3D construct was dissolved, and cells were isolated at days 3, 7, and 14 for transcriptional analysis. Expression of the SG markers K8 and K18 was higher from the 3D construct with (3D/PD+) than without PD (3D/PD); K8 and K18 expression in the 3D/PD construct was similar to with control that MSCs cultured in 2D condition, which implied the key role of PD in SG specification. As compared with the 2D culture condition, 3D administration (PD+) up-regulated SG markers, which indicated that the 3D structure synergistically boosted the MSC differentiation (Fig. 2A).

(A) Transcriptional expression of K8, K18, Fxyd2, Aqp5, and ATP1a1 in 3D-bioprinted cells with and without PD in days 3, 7, and 14 culture by quantitative real-time polymerase chain reaction (qRT-PCR). Data are means SEM. (B) Comparison of SG-specific markers K8 and K18 in 3D-bioprinted cells with and without PD (K8 and K18, red; DAPI, blue; scale bars, 50 m). (C and D) Comparison of SG secretion-related markers ATP1a1 (C) and Ca2+ (D) in 3D-bioprinted cells with and without PD [ATP1a1 and Ca2+, red; 4,6-diamidino-2-phenylindole (DAPI), blue; scale bars, 50 m].

In addition, we tested secretion-related genes to evaluate the function of induced SG cells (iSGCs). Although levels of the ion channel factors of Fxyd2 and ATP1a1 were increased notably in 2D culture with PD and ATP1a1 up-regulated in the 3D/PD construct, all the secretory genes of Fxyd2, ATP1a1, and water transporter Aqp5 showed the highest expression level in the 3D/PD+ construct (Fig. 2A). Considering the remarkable impact, further analysis focused on 3D constructs.

Immunofluorescence staining confirmed the progression of MSC differentiation. At day 7, cells in the 3D/PD+ construct began to express K8 and K18, which was increased at day 14, whereas cells in the 3D/PD construct did not express K8 and K18 all the time (Fig. 2B and fig. S2A). However, the expression of ATP1a1 (ATPase Na+/K+ transporting subunit alpha 1) and free Ca2+ concentration did not differ between cells in the 3D/PD+ and 3D/PD constructs (Fig. 2, C and D). By placing MSCs in such a 3D environment, secretion might be stimulated by rapid cell aggregation without the need for SG lineage differentiation. Cell aggregationimproved secretion might be due to the benefit of cell-cell contact (fig. S2B) (21, 22).

To map the cell fate changes during the differentiation between MSCs and SG cells, we monitored the mRNA levels of epithelial markers such as E-cadherin, occludin, Id2, and Mgat3 and mesenchymal markers N-cadherin, vimentin, Twist1, and Zeb2. The cells transitioned from a mesenchymal status to a typical epithelial-like status accompanied by mesenchymal-epithelial transition (MET), then epithelial-mesenchymal transition (EMT) occurred during the further differentiation of epithelial lineages to SG cells (fig. S3A). In addition, MET-related genes were dynamically regulated during the SG differentiation of MSCs. For example, the mesenchymal markers N-cadherin and vimentin were down-regulated from days 1 to 7, which suggested cells losing their mesenchymal phenotype, then were gradually up-regulated from days 7 to 10 in their response to the SG phenotype and decreased at day 14. The epithelial markers E-cadherin and occludin showed an opposite expression pattern: up-regulated from days 1 to 5, then down-regulated from days 7 to 10 and up-regulated again at day 14. The mesenchymal transcriptional factors ZEB2 and Twist1 and epithelial transcriptional factors Id2 and Mgat3 were also dynamically regulated.

We further analyzed the expression of these genes at the protein level by immunofluorescence staining (figs. S3B and S4). N-cadherin was down-regulated from days 3 to 7 and reestablished at day 14, whereas E-cadherin level was increased from days 3 to 7 and down-regulated at day 14. Together, these results indicated that a sequential and dynamic MET-EMT process underlie the differentiation of MSCs to an SG phenotype, perhaps driving differentiation more efficiently (23). However, the occurrence of the MET-EMT process did not depend on the presence of PD. Thus, a 3D structural factor might also participate in the MSC-specific differentiation (fig. S3C).

To investigate the underlying mechanism of biochemical cues in lineage-specific cell fate, we used quantitative proteomics analysis to screen the ECM factors differentially expressed between PD and dorsal region dermis (DD) because mice had eccrine SGs exclusively present in the pads of their paws, and the trunk skin lacks SGs. In total, quantitative proteomics analyses showed higher expression levels of 291 proteins in PD than DD. Overall, 66 were ECM factors: 23 were significantly up-regulated (>2-fold change in expression). We initially determined the level of proteins with the most significant difference after removing keratins and fibrin: collagen triple helix repeat containing 1 (CTHRC1) and thrombospondin 1 (TSP1) (fig. S5). Western blotting was performed to further confirm the expression level of CTHRC1 and TSP1, and we then confirmed that immunofluorescence staining at different developmental stages in mice revealed increased expression of CTHRC1 in PD with SG development but only slight expression in DD at postnatal day 28, while TSP1 was continuously expressed in DD and PD during development (Fig. 3, A to C). Therefore, TSP1 was required for the lineage-specific function during the differentiation in mice but was not dispensable for SG development.

(A and B) Differential expression of CTHRC1 and TSP1in PD and back dermis (DD) ECM of mice by proteomics analysis (A) and Western blotting (B). (C) CTHRC1 and TSP1 expression in back and plantar skin of mice at different developmental times. (Cthrc1/TSP1, red; DAPI, blue; scale bars, 50 m).

According to previous results of the changes of SG markers, 3D structure and PD were both critical to SG fate. Then, we focused on elucidating the mechanisms that underlie the significant differences observed in 2D and 3D conditions with or without PD treatment. To this end, we performed transcriptomics analysis of MSCs, MSCs treated with PD, MSCs cultured in 3D construct, and MSC cultured in 3D construct with PD after 3-day treatment. We noted that the expression profiles of MSCs treated with 3D, PD, or 3D/PD were distinct from the profiles of MSCs (Fig. 4A). Through Gene Ontology (GO) enrichment analysis of differentially expressed genes, it was shown that PD treatment in 2D condition induced up-regulation of ECM and inflammatory response term, and the top GO term for MSCs in 3D construct was ECM organization and extracellular structure organization. However, for the MSCs with 3D/PD treatment, we found very significant overrepresentation of GO term related to branching morphogenesis of an epithelial tube and morphogenesis of a branching structure, which suggested that 3D structure cues and biochemical cues synergistically initiate the branching of gland lineage (fig S6). Heat maps of differentially expressed ECM organization, cell division, gland morphogenesis, and branch morphogenesis-associated genes were shown in fig. S7. To find the specific genes response to 3D structure cues facilitating MSC reprogramming, we analyzed the differentially expressed genes of four groups of cells (Fig. 4B). The expression of Vwa1, Vsig1, and Hmox1 were only up-regulated with 3D structure stimulation, especially the expression of Hmox1 showed a most significant increase and even showed a higher expression addition with PD, which implied that Hmox1 might be the transcriptional driver of MSC differentiation response to 3D structure cues. Differential expression of several genes was confirmed by quantitative polymerase chain reaction (qPCR): Mmp9, Ptges, and Il10 were up-regulated in all the treated groups. Likewise, genes involving gland morphogenesis and branch morphogenesis such as Bmp2, Tgm2, and Sox9 showed higher expression in 3D/PD-treated group. Bmp2 was up-regulated only in 3D/PD-treated group, combined with the results of GO analysis, we assumed that Bmp2 initiated SG fate through inducing branch morphogenesis and gland differentiation (Fig. 4C).

(A) Gene expression file of four groups of cells (R2DC, MSCs; R2DT, MSC with PD treatment; R3DC, MSC cultured in 3D construct; and R3DT, MSC treated with 3D/PD). (B) Up-regulated genes after treatment (2DC, MSCs; 2DT, MSC with PD treatment; 3DC, MSC cultured in 3D construct; and 3DT, MSC treated with 3D/PD). (C) Differentially expressed genes were further validated by RT-PCR analysis. [For all RT-PCR analyses, gene expression was normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with 40 cycles, data are represented as the means SEM, and n = 3].

To validate the role of HMOX1 and CTHRC1 in the differentiation of MSCs to SG lineages, we analyzed the gene expression of Bmp2 by regulating the expression of Hmox1 and CTHRC1 based on the 3D/PD-treated MSCs. The effects of caffeic acid phenethyl ester (CAPE) and tin protoporphyrin IX dichloride (Snpp) on the expression of Hmox1 were evaluated by quantitative real-time (qRT)PCR. Hmox1 expression was significantly activated by CAPE and reduced by Snpp. Concentration of CTHRC1 was increased with recombinant CTHRC1 and decreased with CTHRC1 antibody. That is, it was negligible of the effects of activator and inhibitor of Hmox1 and CTHRC1 on cell proliferation (fig. S8, A and B). Hmox1 inhibition or CTHRC1 neutralization could significantly reduce the expression of Bmp2, while Hmox1 activation or increased CTHRC1 both activated Bmp2 expression. Furthermore, Bmp2 showed highest expression by up-regulation of Hmox1 and CTHRC1 simultaneously and sharply decreased with down-regulation of Hmox1 and CTHRC1 at the same time (Fig. 5A). Immunofluorescent staining revealed that the expression of bone morphogenetic protein 2 (BMP2) at the translational level with CTHRC1 and Hmox1 regulation showed a similar trend with transcriptional changes (Fig. 5B). Likewise, the expression of K8 and K18 at transcriptional and translational level changed similarly with CTHRC1 and Hmox1 regulation (fig. S9, A and B). These results suggested that CTHRC1 and Hmox1 played an essential role in SG fate separately, and they synergistically induced SG direction from MSCs (Fig. 5C).

(A and B) Transcriptional analysis (A) and translational analysis (PD, MSCs; PD+, MSCs with 3D/PD treatment; CAPE, MSCs treated with 3D/PD and Hmox1 activator; Snpp, MSCs treated with 3D/PD and Hmox1 inhibitor; Cthrc1, MSCs treated with 3D/PD and recombinant CTHRC1; anti, MSCs treated with 3D/PD and CTHRC1 antibody: +/+, MSCs treated with 3D/PD and Hmox1 activator and recombinant CTHRC1; and /, MSCs treated with 3D/PD and Hmox1 inhibitor and CTHRC1 antibody. Data are represented as the means SEM and n = 3) (B) of bmp2 with regulation of CTHRC1 and Hmox1. (C) The graphic illustration of 3D-bioprinted matrix directed MSC differentiation. CTHRC1 is the main biochemical cues during SG development, and structural cues up-regulated the expression of Hmox1 synergistically initiated branching morphogenesis of SG. *P < 0.05.

Next, we sought to assess the repair capacity of iSGCs for in vivo implications, the 3D-printed construct with green fluorescent protein (GFP)labeled MSCs was transplanted in burned paws of mice (Fig. 6A). We measured the SG repair effects by iodine/starch-based sweat test at day 14. Only mice with 3D/PD treatment showed black dots on foot pads (representing sweating), and the number increased within 10 min; however, no black dots were observed on untreated and single MSC-transplanted mouse foot pads even after 15 min (Fig. 6B). Likewise, hematoxylin and eosin staining analysis revealed SG regeneration in 3D/PD-treated mice (Fig. 6C). GFP-positive cells were characterized as secretory lumen expressing K8, K18, and K19. Of note, the GFP-positive cells were highly distributed in K14-positive myoepithelial cells of SGs but were absent in K14-positive repaired epidermal wounds (Fig. 6, D and E). Thus, differentiated MSCs enabled directed restitution of damaged SG tissues both at the morphological and functional level.

(A) Schematic illustration of approaches for engineering iSGCs and transplantation. (B) Sweat test of mice treated with different cells. Photo credit: Bin Yao, Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Sciences, General Hospital of PLA. (C) Histology of plantar region without treatment and transplantation of MSCs and iSGCs (scale bars, 200 m). (D) Involvement of GFP-labeled iSGCs in directed regeneration of SG tissue in thermal-injured mouse model (K14, red; GFP, green; DAPI, blue; scale bar, 200 m). (E) SG-specific markers K14, K19, K8, and K18 detected in regenerated SG tissue (arrows). (K14, K19, K8, and K18, red; GFP, green; scale bars, 50 m).

A potential gap in MSC-based therapy still exists between current understandings of MSC performance in vivo in their microenvironment and their intractability outside of that microenvironment (24). To regulate MSCs differentiation into the right phenotype, an appropriate microenvironment should be created in a precisely controlled spatial and temporal manner (25). Recent advances in innovative technologies such as bioprinting have enabled the complexities in the matrix design and fabrication of regenerative microenvironments (26). Our findings demonstrated that directed differentiation of MSCs into SGs in a 3D-printed matrix both in vitro and in vivo was feasible. In contrast to conventional tissue-engineering strategies of SG regeneration, the present 3D-printing approach for SG regeneration with overall morphology and function offered a rapid and accurate approach that may represent a ready-to-use therapeutic tool.

Furthermore, bioprinting MSCs successfully repaired the damaged SG in vivo, suggesting that it can improve the regenerative potential of exogenous differentiated MSCs, thereby leading to translational applications. Notably, the GFP-labeled MSC-derived glandular cells were highly distributed in K14-positive myoepithelial cells of newly formed SGs but were absent in K14-positive repaired epidermal wounds. Compared with no black dots were observed on single MSC-transplanted mouse foot pads, the black dots (representing sweating function) can be observed throughout the entire examination period, and the number increased within 10 min on MSC-bioprinted mouse foot pads. Thus, differentiated MSCs by 3D bioprinting enabled exclusive restitution of damaged SG tissues morphologically and functionally.

Although several studies indicated that engineering 3D microenvironments enabled better control of stem cell fates and effective regeneration of functional tissues (2730), there were no studies concerning the establishment of 3D-bioprinted microenvironments that can preferentially induce MSCs differentiating into glandular cells with multiple tissue phenotypes and overall functional tissue. To find an optimal microenvironment for promoting MSC differentiation into specialized progeny, biochemical properties are considered as the first parameter to ensure SG specification. In this study, we used mouse PD as the main composition of a tissue-specific ECM. As expected, this 3D-printed PD+ microenvironment drove the MSC fate decision to enhance the SG phenotypic profile of the differentiated cells. By ECM differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator of 3D-printed matrix for SG specification. TSP1 was required for the lineage-specific function during the differentiation in mice but was not dispensable for SG development. Thus, we identified CTHRC1 as a specific factor during SG development. To our knowledge, this is the first demonstration of CTHRC1 involvement in dictating MSC differentiation to SG, highlighting a potential therapeutic tool for SG injury.

The 3D-printed matrix also provided architectural guides for further SG morphogenesis. Our results clearly show that the 3D spatial dimensionality allows for better cell proliferation and aggregation and affect the characteristics of phenotypic marker expression. Notably, the importance of 3D structural cues on MSC differentiation was further proved by MET-EMT process during differentiation, where the influences did not depend on the presence of biochemical cues. To fully elucidate the underlying mechanisms, we first examined how 3D structure regulating stem cell fate choices. According to our data, Hmox1 is highly up-regulated in 3D construct, which were supposed to response to hypoxia, with a previously documented role in MSC differentiation (31, 32). It is suggested that 3D microenvironment induced rapid cell aggregation leading to hypoxia and then activated the expression of Hmox1.

Through regulation of the expression of Hmox1 and addition or of CTHRC1 in the matrix, we confirmed that each of them is critical for SG reprogramming, respectively. Thus, biochemical and structural cues of 3D-printed matrix synergistically creating a microenvironment could enhance the accuracy and efficiency of MSC differentiation, thereby leading to resulting SG formation. Although we further need a more extensive study examining the role of other multiple cues and their possible overlap function in regulating MSC differentiation, our findings suggest that CTHRC1 and Hmox1 provide important signals that cooperatively modulate MSC lineage specification toward sweat glandular lineage. The 3D structure combined with PD stimulated the GO functional item of branch morphogenesis and gland formation, which might be induce by up-regulation of Bmp2 based on the verification of qPCR results. Although our results could not rule out the involvement of other factors and their possible overlapping role in regulating MSC lineage specification toward SGs, our findings together with several literatures suggested that BMP2 plays a critical role in inducing branch morphogenesis and gland formation (3335).

In summary, our findings represented a novel strategy of directing MSC differentiation for functional SG regeneration by using 3D bioprinting and pave the way for a potential therapeutic tool for other complex glandular tissues as well as further investigation into directed differentiation in 3D conditions. Specifically, we showed that biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation, and our results highlighted the importance of 3D-printed matrix cues as regulators of MSC fate decisions. This avenue opens up the intriguing possibility of shifting from genetic to microenvironmental manipulations of cell fate, which would be of particular interest for clinical applications of MSC-based therapies.

The main aim and design of the study was first to determine whether by using 3D-printed microenvironments, MSCs can be directed to differentiate and regenerate SGs both morphologically and functionally. Then, to investigate the underlying molecular mechanism of biochemical and structural cues of 3D-printed matrix involved in MSCs reprogramming. The primary aims of the study design were as follows: (i) cell aggregation and proliferation in a 3D-bioprinted construct; (ii) differentiation of MSCs at the cellular phenotype and functional levels in the 3D-bioprinted construct; (iii) the MET-EMT process during differentiation; (iv) differential protein expression of the SG niche in mice; (v) differential genes expression of MSCs in 3D-bioprinted construct; (vi) the key role of CTHRC1 and HMOX1 in MSCs reprogramming to SGCs; and (vii) functional properties of regenerated SG in vivo.

Gelatin (Sigma-Aldrich, USA) and sodium alginate (Sigma-Aldrich, USA) were dissolved in phosphate-buffered saline (PBS) at 15 and 1% (w/v), respectively. Both solutions were sterilized under 70C for 30 min three times at an interval of 30 min. The sterilized solutions were packed into 50-ml centrifuge tubes, stored at 4C, and incubated at 37C before use.

From wild-type C57/B16 mice (Huafukang Co., Beijing) aged 5 days old, dermal homogenates were prepared by homogenizing freshly collected hairless mouse PD with isotonic phosphate buffer (pH 7.4) for 20 min in an ice bath to obtain 25% (w/v) tissue suspension. The supernatant was obtained after centrifugation at 4C for 20 min at 10,000g. The DNA content was determined using Hoechst 33258 assay (Beyotime, Beijing). The fluorescence intensity was measured to assess the amount of remaining DNA within the decellularized ECMs and the native tissue using a fluorescence spectrophotometer (Thermo Scientific, Evolution 260 Bio, USA). The GAGs content was estimated via 1,9-dimethylmethylene blue solution staining. The absorbance was measured with microplate reader at wavelength of 492 nm. The standard curve was made using chondroitin sulfate A. The total COL (Collagen) content was determined via hydroxyproline assay. The absorbance of the samples was measured at 550 nm and quantified by referring to a standard curve made with hydroxyproline.

MSCs were bioprinted with matrix materials by using an extrusion-based 3D bioprinter (Regenovo Co., Bio-Architect PRO, Hangzhou). Briefly, 10 ml of gelatin solution (10% w/v) and 5 ml of alginate solution (2% w/v) were warmed under 37C for 20 min, gently mixed as bioink and used within 30 min. MSCs were collected from 100-mm dishes, dispersed into single cells, and 200 l of cell suspension was gently mixed with matrix material under room temperature with cell density 1 million ml1. PD (58 g/ml) was then gently mixed with bioink. Petri dishes at 60 mm were used as collecting plates in the 3D bioprinting process. Within a temperature-controlled chamber of the bioprinter, with temperature set within the gelation region of gelatin, the mixture of MSCs and matrix materials was bioprinted into a cylindrical construct layer by layer. The nozzle-insulation temperature and printing chamber temperature were set at 18 and 10C, respectively; nozzles with an inner diameter of 260 m were chosen for printing. The diameter of the cylindrical construct was 30 mm, with six layers in height. After the temperature-controlled bioprinting process, the printed 3D constructs were immersed in 100-mM calcium chloride (Sigma-Aldrich, USA) for 3 min for cross-linking, then washed with Dulbeccos modified Eagle medium (DMEM) (Gibco, USA) medium for three times. The whole printing process was finished in 10 min. The 3D cross-linked construct was cultured in DMEM in an atmosphere of 5% CO2 at 37C. The culture medium was changed to SG medium [contains 50% DMEM (Gibco, New York, NY) and 50% F12 (Gibco) supplemented with 5% fetal calf serum (Gibco), 1 ml/100 ml penicillin-streptomycin solution, 2 ng/ml liothyronine sodium (Gibco), 0.4 g/ml hydrocortisone succinate (Gibco), 10 ng/ml epidermal growth factor (PeproTech, Rocky Hill, NJ), and 1 ml/100 ml insulin-transferrin-selenium (Gibco)] 2 days later. The cell morphology was examined and recorded under an optical microscope (Olympus, CX40, Japan).

Fluorescent live/dead staining was used to determine cell viability in the 3D cell-loaded constructs according to the manufacturers instructions (Sigma-Aldrich, USA). Briefly, samples were gently washed in PBS three times. An amount of 1 M calcein acetoxymethyl (calcein AM) ester (Sigma-Aldrich, USA) and 2 M propidium iodide (Sigma-Aldrich, USA) was used to stain live cells (green) and dead cells (red) for 15 min while avoiding light. A laser scanning confocal microscopy system (Leica, TCSSP8, Germany) was used for image acquisition.

The cell-printed structure was harvested and fixed with a solution of 4% paraformaldehyde. The structure was embedded in optimal cutting temperature (OCT) compound (Sigma-Aldrich, USA) and sectioned 10-mm thick by using a cryotome (Leica, CM1950, Germany). The sliced samples were washed repeatedly with PBS solution to remove OCT compound and then permeabilized with a solution of 0.1% Triton X-100 (Sigma-Aldrich, USA) in PBS for 5 min. To reduce nonspecific background, sections were treated with 0.2% bovine serum albumin (Sigma-Aldrich, USA) solution in PBS for 20 min. To visualize iSGCs, sections were incubated with primary antibody overnight at 4C for anti-K8 (1:300), anti-K14 (1:300), anti-K18 (1:300), anti-K19 (1:300), anti-ATP1a1 (1:300), anti-Ki67 (1:300), antiN-cadherin (1:300), antiE-cadherin (1:300), anti-CTHRC1 (1:300), or anti-TSP1 (1:300; all Abcam, UK) and then incubated with secondary antibody for 2 hours at room temperature: Alexa Fluor 594 goat anti-rabbit (1:300), fluorescein isothiocyanate (FITC) goat anti-rabbit (1:300), FITC goat anti-mouse (1:300), or Alexa Fluor 594 goat anti-mouse (1:300; all Invitrogen, CA). Sections were also stained with 4,6-diamidino-2-phenylindole (Beyotime, Beijing) for 15 min. Stained samples were visualized, and images were captured under a confocal microscope.

To harvest the cells in the construct, the 3D constructs were dissolved by adding 55 mM sodium citrate and 20 mM EDTA (Sigma-Aldrich, USA) in 150 mM sodium chloride (Sigma-Aldrich, USA) for 5 min while gently shaking the petri dish for better dissolving. After transfer to 15-ml centrifuge tubes, the cell suspensions were centrifuged at 200 rpm for 3 min, and the supernatant liquid was removed to harvest cells for further analysis.

Total RNA was isolated from cells by using TRIzol reagent (Invitrogen, USA) following the manufacturers protocol. RNA concentration was measured by using a NanoPhotometer (Implen GmbH, P-330-31, Germany). Reverse transcription involved use of a complementary DNA synthesis kit (Takara, China). Gene expression was analyzed quantitatively by using SYBR green with the 7500 Real-Time PCR System (Takara, China). The primers and probes for genes were designed on the basis of published gene sequences (table S1) (National Center for Biotechnology Information and PubMed). The expression of each gene was normalized to that for glyceraldehyde-3-phosphate dehydrogenase and analyzed by the 2-CT method. Each sample was assessed in triplicate.

The culture medium was changed to SG medium with 2 mM CaCl2 for at least 24 hours, and cells were loaded with fluo-3/AM (Invitrogen, CA) at a final concentration of 5 M for 30 min at room temperature. After three washes with calcium-free PBS, 10 M acetylcholine (Sigma-Aldrich, USA) was added to cells. The change in the Fluo 3 fluorescent signal was recorded under a laser scanning confocal microscopy.

Cell proliferation was evaluated through CCK-8 (Cell counting kit-8) assay. Briefly, cells were seeded in 96-well plates at the appropriate concentration and cultured at 37C in an incubator for 4 hours. When cells were adhered, 10 l of CCK-8 working buffer was added into the 96-well plates and incubated at 37C for 1 hour. Absorbance at 450 nm was measured with a microplate reader (Tecan, SPARK 10M, Austria).

Proteomics of mouse PD and DD involved use of isobaric tags for relative and absolute quantification (iTRAQ) in BGI Company, with differentially expressed proteins detected in PD versus DD. Twofold greater difference in expression was considered significant for further study.

Tissues were grinded and lysed in radioimmunoprecipitation assay buffer (Beyotime, Nanjing). Proteins were separated by 12% SDSpolyacrylamide gel electrophoresis and transferred to a methanol-activated polyvinylidene difluoride membrane (GE Healthcare, USA). The membrane was blocked for 1 hour in PBS with Tween 20 containing 5% bovine serum albumin (Sigma-Aldrich, USA) and probed with the antibodies anti-CTHRC1 (1:1000) and anti-TSP1 (1:1000; both Abcam, UK) overnight at 4C. After 2 hours of incubation with goat anti-rabbit horseradish peroxidaseconjugated secondary antibody (Santa Cruz Biotechnology, CA), the protein bands were detected by using luminal reagent (GE Healthcare, ImageQuant LAS 4000, USA).

Total RNA was prepared with TRIzol (Invitrogen), and RNA sequencing was performed using HiSeq 2500 (Illumina). Genes with false discovery rate < 0.05, fold difference > 2.0, and mean log intensity > 2.0 were considered to be significant.

CAPE or Snpp was gently mixed with bioink at a concentration of 10 M. Physiological concentration of CTHRC1 was measured by enzyme linked immunosorbent assay (ELISA) (80 ng/ml), and then recombinant CTHRC1 or CTHRC1 antibody was added into the bioink at a concentration of 0.4 g/ml. The effect of inhibitor and activator was estimated by qRT-PCR or ELISA.

Mice were anesthetized with pentobarbital (100 mg/kg) and received subcutaneous buprenorphine (0.1 mg/kg) preoperatively. Full-thickness scald injuries were created on paw pads with soldering station (Weller, WSD81, Germany). Mice recovered in clean cages with paper bedding to prevent irritation or infection. Mice were monitored daily and euthanized at 30 days after wounding. Mice were maintained in an Association for Assessment and Accreditation of Laboratory Animal Careaccredited animal facility, and procedures were performed with Institutional Animal Care and Use Committeeapproved protocols.

MSCs in 3D-printed constructs with PD were cultured with DMEM for 2 days and then replaced with SG medium. The SG medium was changed every 2 days, and cells were harvested on day 12. The K18+ iSGCs were sorting through flow cytometry and injected into the paw pads (1 106 cells/50 l) of the mouse burn model by using Microliter syringes (Hamilton, 7655-01, USA). Then, mice were euthanized after 14 days; feet were excised and fixed with 10% formalin (Sigma-Aldrich, USA) overnight for paraffin sections and immunohistological analysis.

The foot pads of anesthetized treated mice were first painted with 2% (w/v) iodine/ethanol solution then with starch/castor oil solution (1 g/ml) (Sigma-Aldrich, USA). After drying, 50 l of 100 M acetylcholine (Sigma-Aldrich, USA) was injected subcutaneously into paws of mice. Pictures of the mouse foot pads were taken after 5, 10, and 15 min.

All data were presented as means SEM. Statistical analyses were performed using GraphPad Prism7 statistical software (GraphPad, USA). Significant differences were calculated by analysis of variance (ANOVA), followed by the Bonferroni test when performing multiple comparisons between groups. P < 0.05 was considered as a statistically significant difference.

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/6/10/eaaz1094/DC1

Fig. S1. Biocompatibility of 3D-bioprinted construct and cellular morphology in 2D monolayer culture.

Fig. S2. Expression of SG-specific and secretion-related markers in MSCs and SG cells in vitro.

Fig. S3. Transcriptional and translational expression of epithelial and mesenchymal markers in 3D-bioprinted cells with and without PD.

Fig. S4. Expression of N- and E-cadherin in MSCs and SG cells in 2D monolayer culture.

Fig. S5. Proteomic microarray assay of differential gene expression between PD and DD ECM in postnatal mice.

Fig. S6. GO term analysis of differentially expressed pathways.

Fig. S7. Heat maps illustrating differential expression of genes implicated in ECM organization, cell division, and gland and branch morphogenesis.

Fig. S8. The expression of Hmox1 and the concentration of CTHRC1 on treatment and the related effects on cell proliferation.

Fig. S9. The expression of K8 and K18 with Hmox1 and CTHRC1 regulation.

Table S1. Primers for qRT-PCR of all the genes.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: Funding: This study was supported in part by the National Nature Science Foundation of China (81571909, 81701906, 81830064, and 81721092), the National Key Research Development Plan (2017YFC1103300), Military Logistics Research Key Project (AWS17J005), and Fostering Funds of Chinese PLA General Hospital for National Distinguished Young Scholar Science Fund (2017-JQPY-002). Author contributions: B.Y. and S.H. were responsible for the design and primary technical process, conducted the experiments, collected and analyzed data, and wrote the manuscript. Y.W. and R.W. helped perform the main experiments. Y.Z. and T.H. participated in the 3D printing. W.S. and Z.L. participated in cell experiments and postexamination. S.H. and X.F. collectively oversaw the collection of data and data interpretation and revised the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration - Science...

Skin Stem Cells Comments Off on Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration – Science… | March 5th, 2020

New Delhi: The usage of stem cells to cure or treat a disease or repair the injured tissue is defined as stem cell therapy. The best example of the stem cell treatment is seen in patients suffering from restoring the vision of the damaged eyes, grafting of the skin in severe burnt conditions.

Stem cell treatments for brain or neural diseases like Parkinsons and Alzheimers disease, multiple sclerosis, preventing heart strokes, curing diabetes, kidney disorders, autism, and spinal cord injuries are progressively making their way.

Undifferentiated cells that are able to differentiate and transform into any type of cells of the body when and where needed. They have an enormous potential to repair, heal and regenerate. Stem cells come from blood, bone marrow, umbilical cord blood and adipose tissue.

Autologous stem cell therapy: Patient receives stem cells from his/her own body

Allogeneic stem cell therapy: Patient receives the stem cells donated by another individual

Autologous stem cell therapy is better than allogeneic stem cell therapy as chances of mismatching are not there and they pose the minimum risk of immune rejection. Also, no side effects or adverse effects are seen as a persons own blood cells are used. They start the healing process immediately in a natural way.

The usage of stem cells to cure or treat a disease or repair the injured tissue is defined as stem cell therapy. Stem cells can be obtained from the bone marrow, adipose tissues etc. Due to their tremendous potential to prevent and to treat various health conditions and to repair the injured tissues global research investigation is continuously being done as to explore the maximum advantage of these cell lines.

The best example of the stem cell treatment is seen in patients suffering from restoring the vision of the damaged eyes, grafting of the skin in severe burnt conditions. Stem cell treatments for brain or neural diseases like Parkinsons and Alzheimers disease, multiple sclerosis, preventing heart strokes, curing diabetes, kidney disorders, autism, and spinal cord injuries are progressively making their way.

Depending upon the disease, different stem cell source can be used in a specific condition. The procedure may involve the extraction of stem cells from adipose tissue-derived stem cells with the combination of PRP (Platelet-rich plasma) or can be obtained from bone marrow that can differentiate into progenitor cells that differentiate into various other tissues which can help in the therapy.

The stem cells are isolated from the bone marrow or adipose tissues followed by their processing and enrichment under sterile conditions. These activated stem cells are placed back into the patients body at the target site for repairing the damaged tissue. It is necessary that the stem cells are injected in the specific area of injury as only then the desired results will be achieved.

Adipose stem cells are preferred over bone marrow stem cells as they are easy to isolate and contain a higher number of stem cells.

The stem cells injections are gaining much interest because it is devoid of the painful procedure, takes less time in comparison to surgery, there are no host and recipient rejections as stem cells are harvested from the patients body itself and a targeted delivery system is available.

The stem cells obtained are processed in a sophisticated stem cell lab and after activation is inserted back into the host with the help of intravenous, intramuscular, intraarterial, intradermal and intrathecal injections as per the requirement of the treatment process.

What is the use of anaesthetics and why? Usually, local anaesthetics are used during a stem cell procedure to numb the area but sometimes general anaesthesia is also given while extracting the stem cells from bone marrow. But it is necessary to find out what anaesthetic your doctor uses during orthopaedic stem cell treatments.

A number of anaesthetics have been found to kill the stem cells thus; the treatments end result will greatly depend on the use of anaesthetics. Some anaesthetics very well sync with the stem cell and hence, aid in the treatment.

Stem cells are to be extracted and processed in a clean room, under aseptic conditions maintaining a controlled environment. The doctor should explain the entire process and the number of viable stem cells infused into the patient during the process. Also, the precision of the injections to provide good quality of stem cells at the site of injury will help in better and faster recovery of the patients damaged area.

Cost of the treatment and its duration varies from one patient to another. The disease which needs to be cured, the severity, age factor, health condition, etc, define the duration of the therapy. One may respond during the treatment phase itself while the other may show results after a few sessions or weeks. Depending upon the disease diagnosed, the stem cells extracted, duration of the therapy, other adjuvants used in the process, the cost of the stem cell therapy can vary.

It is essential that after the stem cell therapy the patient should visit the stem cell doctor for recuperation therapies. The primary goals of such therapy is the prevention of secondary complications, analysis of the recovery of motor, sensory and all the bodily functioning, psychological support/counselling for depression, mood swings or anxiety etc. and reintegration into the community.

There can be different sets of precautions which need to be followed at various steps for the recovery of the damaged tissues. The treatment and post-treatment conditions may vary from person to person depending upon the disease and the severity.

Stem cell therapy has shown results in treating serious ailments like leukaemia, grafting tissues, autism, orthopaedic conditions and skin problems etc. Stem Cell Therapy has been successfully used in the treatment of around 80 serious disorders.

Survival rates among patients who received stem cell treatment are significantly high, whether cell donors are related or unrelated to them. With the ongoing research around the world, scientists are exploring new possibilities in which a number of life-threatening diseases can be prevented and cured hence, the stem cells have proved to be promising in the near future as many aspects are yet to be revealed.

Read: Egg stem cells do not exist, says researchers

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10 things to know about stem cell therapy - Newsd.in

Skin Stem Cells Comments Off on 10 things to know about stem cell therapy – Newsd.in | March 5th, 2020

I consider my nighttime skincare routine as me time. I always double cleanse; first with Bioderma Sensibio H20 Micellar Water, 10.80, and then I use Rodial Pink Diamond Cleansing Balm, 55, and massage it into my skin. Its a really light and gentle balm that has enough slip for me to be able to easily move it around my face, and it helps dissolve any left over SPF and make-up while also getting rid of the days dirt and grime.

After a good 10-15 minute cleanse, I sweep Pestle and Mortar NMF Lactic Acid Toner, 28, around my face. Lactic acid works underneath the skin, helping to get rid of dead skin cells without dehydrating my skin. Then I press SkinCeuticals HA Intensifer, 90, into my skin to help increase hydration levels.

I use my final product once Im in bed; Decleors Bigarade Neroli Night Balm, 45, which I do a deep pressure massage with and then I finish off using a gua sha to help drain any fluids and relax the muscles.

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3 skin experts share their morning and evening skincare routines - Stylist Magazine

Skin Stem Cells Comments Off on 3 skin experts share their morning and evening skincare routines – Stylist Magazine | March 5th, 2020

A population of stem cells with the ability to generate new bone has been newly discovered by a group of researchers at the UConn School of Dental Medicine.

In the journal STEM CELLS, lead investigator Dr. Ivo Kalajzic, professor of reconstructive sciences, postdoctoral fellows Dr. Sierra Root and Dr. Natalie Wee, and collaborators at Harvard, Maine Medical Research Center, and the University of Auckland present a new population of cells that reside along the vascular channels that stretch across the bone and connect the inner and outer parts of the bone.

This is a new discovery of perivascular cells residing within the bone itself that can generate new bone forming cells, said Kalajzic. These cells likely regulate bone formation or participate in bone mass maintenance and repair.

Stem cells for bone have long been thought to be present within bone marrow and the outer surface of bone, serving as reserve cells that constantly generate new bone or participate in bone repair. Recent studies have described the existence of a network of vascular channels that helped distribute blood cells out of the bone marrow, but no research has proved the existence of cells within these channels that have the ability to form new bones.

In this study, Kalajzic and his team are the first to report the existence of these progenitor cells within cortical bone that can generate new bone-forming cells osteoblasts that can be used to help remodel a bone.

To reach this conclusion, the researchers observed the stem cells within an ex vivo bone transplantation model. These cells migrated out of the transplant, and began to reconstruct the bone marrow cavity and form new bone.

While this study shows there is a population of cells that can help aid bone formation, more research needs to be done to determine the cells potential to regulate bone formation and resorption.

This study was funded by the Regenerative Medicine Research Fund (RMRF; 16-RMB-UCHC-10) by CT Innovations and by National Institute of Arthritis and Musculoskeletal and Skin.

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UConn Researchers Discover New Stem Cells That Can Generate New Bone - UConn Today

Bone Marrow Stem Cells Comments Off on UConn Researchers Discover New Stem Cells That Can Generate New Bone – UConn Today | March 5th, 2020

The Global Stem Cells Market is expected to grow from USD 115.46 Million in 2018 to USD 325.84 Million by the end of 2025 at a Compound Annual Growth Rate (CAGR) of 15.97%.

The Stem Cells Market research presents a study by combining primary as well as secondary research. The report gives insights on the key factors concerned with generating and limiting Stem Cells market growth.

Additionally, the report also studies competitive developments, such as mergers and acquisitions, new partnerships, new contracts, and new product developments in the global Stem Cells market. The past trends and future prospects included in this report makes it highly comprehensible for the analysis of the market. Moreover, the latest trends, product portfolio, demographics, geographical segmentation, and regulatory framework of the Stem Cells market have also been included in the study.

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Stem Cells Market Segment by Manufacturers includes: The report deeply explores the recent significant developments by the leading vendors and innovation profiles in the Global Stem Cells Market including are Anterogen Co., Ltd., Holostem Terapie Avanzate Srl, Medipost Co., Ltd., Osiris Therapeutics, Inc., Pharmicell Co., Ltd., Allosource, JCR Pharmaceuticals Co., Ltd., Nuvasive, Inc., and RTI Surgical, Inc.. On the basis of Cell Source, the Global Stem Cells Market is studied across Adipose Tissue-Derived Mesenchymal Stem Cells, Bone Marrow-Derived Mesenchymal Stem Cells, and Cord Blood/Embryonic Stem Cells.On the basis of Type, the Global Stem Cells Market is studied across Allogeneic Stem Cell Therapy and Autologous.On the basis of Therapeutic Application , the Global Stem Cells Market is studied across Cardiovascular Diseases, Gastrointestinal Diseases, Musculoskeletal Disorders, Surgeries, and Wounds and Injuries.

Global Stem Cells market report covers all the major participants and the retailers will be in conscious of the development factors, market barriers & threats, and the opportunities that the market will offer in the near future. The report also features the historical revenue of the market; industry trends, market volume, and consumption in order to gain perceptions about the political and technical environment of the Stem Cells market share.

This report focuses on the Stem Cells in Global market, especially in

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The report gives detailed analysis in terms of qualitative and quantitative data pertaining to the projected potential opportunities that influence markets growth for the forecast period. With a major focus on the key elements and segments of the global Stem Cells market that might affect the growth prospects of the market, making it a highly informative document.

Major Points covered in this Report:

Market Segmentation:

Regional market analysis

The content of the study subjects includes a total of 15 chapters:

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About Us:We, Regal Intelligence, aim to change the dynamics of market research backed by quality data. Our analysts validate data with exclusive qualitative and analytics driven intelligence. We meticulously plan our research process and execute in order to explore the potential market for getting insightful details. Our prime focus is to provide reliable data based on public surveys using data analytics techniques. If you have come here, you might be interested in highly reliable data driven market insights for your product/service,reach us here 24/7.

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Stem Cells Market Top Impacting Factors to Growth of the Industry by 2025 - Bandera County Courier

Bone Marrow Stem Cells Comments Off on Stem Cells Market Top Impacting Factors to Growth of the Industry by 2025 – Bandera County Courier | March 5th, 2020

VANCOUVER, Washington, March 04, 2020 (GLOBE NEWSWIRE) -- CytoDyn Inc. (CYDY), (CytoDyn or the Company"), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today the treatment of the first patient in its Phase 2 clinical trial for graft-versus-host disease (GvHD) under the modified trial protocol.

The modified protocol now includes reduced intensity conditioning (RIC) patients and an open-label design under which all enrollees receive leronlimab. The modified protocol also provides for a 50% increase in the dose of leronlimab to more closely mimic preclinical dosing. The next review of data by the independent data monitoring committee (iDMC) will occur following enrollment of 10 patients under the amended protocol after each patient has been dosed for 30 days.

Nader Pourhassan, Ph.D., president and chief executive officer of CytoDyn, added, GvHD is a life-threatening complication following bone marrow transplantation in patients with leukemia who have compromised immune systems due to treatment with aggressive cancer therapies. We selected GvHD as one of our immunology indications for leronlimab, as it targets and masks the CCR5 receptor on T cells. This receptor on T cells is an important mediator of inflammatory diseases including GvHD, especially in organ damage that is the most frequent cause of death in these patients. Dr. Pourhassan concluded that, Based upon the compelling results in our preclinical studies, we are optimistic about the opportunities for leronlimab to provide a therapy for transplant patients to mitigate GvHD.

The Companys preclinical study by Denis R. Burger, Ph.D., CytoDyns former Chief Science Officer, and Daniel Lindner, M.D., Ph.D. of the Department of Translational Hematology and Oncology Research, The Cleveland Clinic, was published online in the peer-reviewed journal Biology of Blood and Marrow Transplantation.

The Company previously reported that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to leronlimab (PRO 140) for the prevention of GvHD. Orphan drug designation is granted to development-stage drugs that have shown promise in addressing serious medical needs for patients living with rare conditions. This designation provides CytoDyn with various incentives and benefits including seven years of U.S. market exclusivity for leronlimab (PRO 140) in GvHD, subject to FDA approval for use in this indication.

About Graft-versus-Host Disease (GvHD)Graft-versus-host disease is a risk when patients receive the transplant of bone marrow stem cells donated from another person. GvHD occurs when the donors immune cells attack the patients normal cells. GvHD can be acute or chronic. Its severity depends on the differences in tissue type between patient and donor. The older the patient, the more frequent and serious the reaction may be. Acute GvHD can occur soon after the transplanted cells begin to appear in the recipient and can range from mild, moderate or severe, and be life-threatening if its effects are not controlled. Certain approved drugs exist that can help prevent or lessen GvHD. However, GvHD does not always respond to these treatments, and it can still result in fatal outcomes. Furthermore, many deaths related to GvHD occur because of infections that develop in patients whose immune systems are suppressed by such drugs.

About Leronlimab (PRO 140)The U.S. Food and Drug Administration (FDA) has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer. Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases including NASH. Leronlimab has successfully completed nine clinical trials in over 800 people, including meeting its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients).

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In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab can significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

In the setting of cancer, research has shown that CCR5 plays an important role in tumor invasion and metastasis. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn is therefore conducting aPhase 1b/2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019. Additional research is being conducted with leronlimab in the setting of cancer and NASH with plans to conduct additionalclinical studies when appropriate.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation and may be important in the development of acute GvHD and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to further support the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD and that blocking this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to leronlimab for the prevention of GvHD.

About CytoDynCytoDyn is a biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a key role in the ability of HIV to enter and infect healthy T-cells. The CCR5 receptor also appears to be implicated in tumor metastasis and in immune-mediated illnesses, such as GvHD and NASH. CytoDyn has successfully completed a Phase 3 pivotal trial with leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to seek FDA approval for leronlimab in combination therapy and plans to complete the filing of a Biologics License Application (BLA) in the first quarter of 2020 for that indication. CytoDyn is also conducting a Phase 3 investigative trial with leronlimab as a once-weekly monotherapy for HIV-infected patients and plans to initiate a registration-directed study of leronlimab monotherapy indication, which if successful, could support a label extension. Clinical results to date from multiple trials have shown that leronlimab can significantly reduce viral burden in people infected with HIV with no reported drug-related serious adverse events (SAEs). Moreover, results from a Phase 2b clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients, with some patients on leronlimab monotherapy remaining virally suppressed for more than five years. CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and a Phase 1b/2 clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is atwww.cytodyn.com.

Forward-Looking StatementsThis press releasecontains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. The Companys forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i)the sufficiency of the Companys cash position, (ii)the Companys ability to raise additional capital to fund its operations, (iii) the Companys ability to meet its debt obligations, if any, (iv)the Companys ability to enter into partnership or licensing arrangements with third parties, (v)the Companys ability to identify patients to enroll in its clinical trials in a timely fashion, (vi)the Companys ability to achieve approval of a marketable product, (vii)the design, implementation and conduct of the Companys clinical trials, (viii)the results of the Companys clinical trials, including the possibility of unfavorable clinical trial results, (ix)the market for, and marketability of, any product that is approved, (x)the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Companys products, (xi)regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii)general economic and business conditions, (xiii)changes in foreign, political, and social conditions, and (xiv)various other matters, many of which are beyond the Companys control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form10-K, and any risk factors or cautionary statements included in any subsequent Form10-Q or Form8-K, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.

CYTODYN CONTACTSInvestors: Dave Gentry, CEORedChip CompaniesOffice: 1.800.RED.CHIP (733.2447)Cell: 407.491.4498dave@redchip.com

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CytoDyn Treats First Patient with Leronlimab in Phase 2 Trial for GvHD under Modified Trial Protocol - Yahoo Finance

Bone Marrow Stem Cells Comments Off on CytoDyn Treats First Patient with Leronlimab in Phase 2 Trial for GvHD under Modified Trial Protocol – Yahoo Finance | March 5th, 2020

The latest Stem Cell Therapy market study offers an all-inclusive analysis of the major strategies, corporate models, and market shares of the most noticeable players in this market. The study offers a thorough analysis of the key persuading factors, market figures in terms of revenues, segmental data, regional data, and country-wise data. This study can be described as most wide-ranging documentation that comprises all the aspects of the evolving Stem Cell Therapy market.

The research report provides deep insights into the global market revenue, parent market trends, macro-economic indicators, and governing factors, along with market attractiveness per market segment. The report provides an overview of the growth rate of Stem Cell Therapy market during the forecast period, i.e., 20202027. Most importantly, the report further identifies the qualitative impact of various market factors on market segments and geographies. The research segments the market on the basis of product type, application, technology, and region. To offer more clarity regarding the industry, the report takes a closer look at the current status of various factors including but not limited to supply chain management, niche markets, distribution channel, trade, supply, and demand and production capability across different countries.

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Stem cell therapy is a technique which uses stem cells for the treatment of various disorders. Stem cell therapy is capable of curing broad spectrum of disorders ranging from simple to life threatening. These stem cells are obtained from different sources, such as, adipose tissue, bone marrow, embryonic stem cell and cord blood among others. Stem cell therapy is enables to treat more than 70 disorders, including degenerative as well as neuromuscular disorders. The ability of a stem cell to renew itself helps in replacing the damaged areas in the human body.

MARKET DYNAMICSIncrease in the number of stem cell banking facilities and rising awareness on the benefits of stem cell for curing various disorders are expected to drive the market during the forecast period. Rise in number of regulations to promote stem cell therapy and increase in number of funds for research in developing countries are expected to offer growth opportunities to the market during the coming years.

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The research provides answers to the following key questions:

The study conducts SWOT analysis to evaluate strengths and weaknesses of the key players in the Stem Cell Therapy market. Further, the report conducts an intricate examination of drivers and restraints operating in the market. The report also evaluates the trends observed in the parent market, along with the macro-economic indicators, prevailing factors, and market appeal according to different segments. The report also predicts the influence of different industry aspects on the Stem Cell Therapy market segments and regions.

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It is extremely vital to have an impartial understanding of market opinions for a strategy. Our insights provide a keen view on the market sentiment. We keep this reconnaissance by engaging with Key Opinion Leaders of a value chain of each industry we track.

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Stem Cell Therapy Market Segmented by Region/Country: North America, Europe, Asia Pacific, Middle East & Africa, and Central & South America

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Stem Cell Therapy Market 2020 To 2027-Expanding Worldwide with Top Players Future Business Scope and Investment Analysis Report - Monroe Scoop

Bone Marrow Stem Cells Comments Off on Stem Cell Therapy Market 2020 To 2027-Expanding Worldwide with Top Players Future Business Scope and Investment Analysis Report – Monroe Scoop | March 5th, 2020

After performing well on the stock market last year -- with shares climbing by 37.3% -- Incyte's (NASDAQ:INCY) stock is down by 11% year to date. And while it would be easy to attribute this poor performance to the COVID-19 epidemic -- which has now spread to more than 50 countries and is hurting the stock market -- the fact is, Incyte's struggles predate these developments.In early January, before most of us had even heard of the coronavirus, Incyte's shares dropped by about 12% after the company reported disappointing results from a pivotal phase 3 clinical trial.

The clinical trial investigated the efficacy of itacitinib and corticosteroids as a combination treatment for treatment-naive acute graft-versus-host disease (GVHD), a condition that can develop in a patient following a stem cell transplant. The treatment failed to meet its primary or secondary endpoints. Despite this setback, Incyte has a plan to get back on the right track, and here are two things that could help the company do just that.

Image source: Getty Images.

Incyte's top selling-product is Jakafi, which treats several conditions, including a rare bone marrow cancer called myelofibrosis. Jakafi also treats patients with polycythemia vera, a condition that leads to an abnormal increase in the production of red blood cells.Lastly, in May 2019, the U.S. Food and Drug Administration (FDA) approved Jakafi for the treatment of steroid-refractory acute GVHD, a condition that occurs when a patient receives a stem cell transplant and the donor's cells trigger an immune response and attack the recipient's organs.Incidences of this condition number about 5,700 cases a year.

Also, steroid-refractory acute GVHD has a one-year mortality rate of about 70%.Jakafi is the first and only FDA-approved treatment for steroid-refractory acute GVHD. Thanks to this relatively new indication, sales of Jakafi could continue growing, as they have been doing for the past few years. During the fourth quarter, Jakafi's net product revenue was $466.5 million, 23% higher than the year-ago period. For the full year, Jakafi's net product revenue was $1.7 billion, a 21% increase compared to 2018.According to Incyte's executive vice president, Barry P. Flannelly, "Patient demand continued to drive the uptake of Jakafi and growth was strong across all three indications."

Furthermore, Incyte collects royalty revenues from Novartis (NYSE:NVS), which holds the rights to Jakafi outside the U.S. Incyte's royalty revenue for Jakafi for the fourth quarter and the full year were $65 million and $225.9 million, respectively, which represented an increase of 17% for the fourth quarter and 16% for the full year.

According to Incyte, Jakafi has been growing its revenue at a compound annual growth rate of 29% since 2016. And the company hopes its crown jewel will continue performing well in the future. Incyte's CEO Herve Hoppenot said, "On the commercial side, we will work to drive continued Jakafi growth in all three indications."

While Jakafi is performing well, Incyte does rely heavily on this product. During the fourth quarter, Jakafi's net product revenue accounted for about 80.5% of the company's total revenue. Fortunately, Incyte is trying to decrease its top-line exposure to its top-selling drug. In February, Incyte submitted capmatinib to the FDA as a potential treatment for an aggressive type of non-small cell lung cancer (NSCLC) called metastatic MET exon 14 skipping (METex14) mutated NSCLC.

There are currently no approved therapies that specifically target this type of NSCLC, which occurs in 3% to 4% of advanced NSCLC cases. Lung cancer is the most common type of cancer in the world, and NSCLC is the most common form of lung cancer. The FDA granted capmatinib a priority review designation, which means the review process for this drug will go faster than usual.

Also, in November 2019, Incyte submitted a New Drug Application to the FDA for pemigatinib as a potential treatment for cholangiocarcinoma, a rare cancer that affects about 0.3 to 3.4 per 100,000 people in North America and Europe. The FDA also granted pemigatinib priority review.In addition to those products that are currently being reviewed by regulatory authorities, Incyte boasts several more pipeline candidates for a variety of other conditions.This could help the company become less reliant on Jakafi in the future.

Incyte's heavy reliance on Jakafi remains a concern, and for that reason, Incyte probably isn't a strong buy. However, Jakafi's revenue should continue climbing, and unless Incyte runs into regulatory roadblocks, it should have several more products to drive its sales even higher. In short, investors should keep an eye on this biotech company.

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These 2 Things Will Help Incytes Stock Rebound - Motley Fool

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Why is it that when a woman runs for an office or does something remarkable so very often the first thing people say is look at her hair or WHAT is she wearing! Well, there is a woman whose photos adorn the halls of the volunteer organization where I volunteer. And because she is the founder of the organization there are lots of photos in the office and in books about the history of the organization. The organization is Hadassah, The Womens Zionist Organization of America. The woman, the founder, is Henrietta Szold (1860-1945).

When I look at her photos, I dont focus on her hair, which changed little over the decades of her work. I dont look at the black pocketbook she often carried which seems not to have changed over the decades of her work. I dont think about her shoes, which were sturdy and usually black. Nope when I look at Miss Henrietta Szolds photo the first thing I think of look at how strong she is, look at the determination and purpose in her eyes, look at what those eyes have seen and those hands have touched. The rest unimportant and anecdotal.

As we are commemorating Womens History and Womens Empowerment Month in March, its very appropriate to tell you that even before Henrietta started Hadassah in a New York City synagogue in 1912 with a study group, she had, in her young life, already broken gender barriers and established institutions. Henrietta started the first night school for immigrants in the US and she studied at the Jewish Theological Seminary in an era when the idea of a female rabbi was unthinkable. An empowered woman look no further absolutely.

When Henriettas eyes first saw the disease and living conditions of the Jews in pre-state Israel on a trip with her mother in 1911, her mission of practical Zionism and her purpose were born. When you read her letters looking for funding or in subsequent years, letters between her and the nurses she sent over to provide pasteurized milk to babies and new moms, and to set up public health stations in Jerusalem to fight off the flies on the eyes of children suffering from trachoma, her words are full of determination and, excuse the old fashioned word gumption. This woman had moxie, this woman had chutzpah, this woman had guts. And thank G-d she did. Because she and her womens organization built the State of Israel. Hadassah created the medical infrastructure of Palestine and continues to do so today in Israel, a mere 108 years later. When there is purpose to what you are committed to and that purpose is accompanied by action there can be longevity. How about an organization that looks forward to the next 100 years? How about volunteers that are active for decades?

They say the proof is in the pudding, that you can judge something only once you have used or experienced it. So: Been there. Done that. Doing it.

Ive been a life member of Hadassah for 54 years, worked in just about every capacity and position at every possible level of the organization. I have gone to Israel so many times but when I juxtapose the memories of my first visit in 1966 with my most recent visit in 2018, WOW, the differences are staggering. Close to the top of the list are the ongoing changes at Hadassah Hospitals and Youth Villages. In the early years, beginning in 1913 when Henrietta sent over the first two nurses, Hadassah Hospitals and Clinics covered the map and over the years. Hadassah and the Hadassah Medical Organization (HMO) created many firsts the first medical school, dental school, nursing school, cancer institute, childrens hospice, ambulatory surgery center, ER unit for premature babies, and trauma treatment center in Israel.

Today the two hills of healing stand at opposite ends of Jerusalem Mt. Scopus (opened in 1939, closed in 1948, reopened in 1975) and the Ein Kerem campus, a tertiary care facility, built in 1961 as Ben Gurion told Hadassah to build in the southwest outskirts of Jerusalem and the city would grow out to it. Which is just what happened. Today, a light rail and bus bring people from all over the area to the hospital. In 2012, the Sarah Wetsman Davidson Hospital Tower opened adding 500 beds and 20 operating theaters. In 2020, Hadassah is re-imagining and re-energizing the campus with its 360 Degrees of Healing Campaign.

Hadassah Hospitals were first in Israel with heart, liver, lung and bone marrow transplants, computer-guided hip replacement (first in the world), macular degeneration clinical trial using embryonic stem cells to repair vision (second in the world) and bone marrow registry for Arabs (only one in the world). Hadassah Medical Organization (HMO) triage procedures and surgical techniques developed by Hadassah doctors were used following the Boston Marathon bombing. HMO doctors and nurses have been first responders in the Philippines, Haiti, Indonesia and Thailand in the wake of natural disasters. Hadassah doctors recently brought humanitarian spinal surgery to Ethiopia.

No rest for this woman she found more purpose and then, more purpose, as time went on.

As a 70-year-old woman, Henrietta was a member of the Palestine Zionist Executive, the Jewish Agency Executive and the Vaad Leumi. Photos show her as often being the only woman in the room. In these capacities she directed the health/educational development and social services of the population. And then, Henrietta took over the daily operations of Youth Aliyah in Palestine. Youth Aliyah was created to bring Jewish children out of Nazi Germany and bring them to Palestine.

In 1943, Henrietta waited in the cold at the Atlit Detention Camp as 750 children from Iran disembarked a train (120 followed a few months later), saved from the atrocities of Nazi Germany. Hadassah joined the life-saving work of Youth Aliyah and continues to be a major supporter to this day. Today, Hadassah-supported youth villages, Meir Shfeyah, Ramat Hadassah Szold and Hadassah Neurim, set at-risk children in Israel on the road to success and since its beginning, more than 300,000 young people from 80 lands have graduated from Youth Aliyah.

Always with an eye to the future, Henrietta Szolds connection to Young Judaea, began in 1909, when she prompted the Federation of American Zionists to call for a junior Zionist convention of delegates from Zionist youth societies. Young Judaea was formally established as a national Zionist youth organization at that New York convention. And then, under the leadership of Henrietta Szold, the department of education was formed by the Zionist Organization of America (ZOA), which briefly sponsored Young Judaea from 1918 to 1921. Over the years, there were many different connections between Henrietta, Hadassah and Young Judaea. Today, Hadassah and Young Judaea continue their connection through their shared mission to forge a strong commitment to Jewish life, instill a love of Israel and Zionism, connect American kids to Israel through education and programs, develop leaders for the Jewish community, and advocacy. Henrietta Szold and Hadassah in the room!

Today Hadassah has 300,000 members, Associates and supporters. It is the largest Jewish womens membership organization in the United States. With members in every Congressional district, Hadassahs advocacy work in spear-heading important legislation, most recently, the Never Again Education Act working to ensure Holocaust education in public schools, is a direct modern-day application of Henriettas legacy and an illustration of purpose with action. Hadassah women are in the room!

So, I think you can see that Henrietta started a run a run of practical Zionism that stretches across decades and centuries. A run I am proud to be part of since it has enabled me to work for Israel while living here in New York. It has allowed me to make differences around the world through medical research and protocols that are shared. Four generations of life members in my family. Three generations of Hadassah Presidents in my family. Once I make our new grandson an Associate, five generations of men affiliated with Hadassah. For me, personally, Hadassah is a family affair.

Today Hadassah strives to empower women of all ages to make a difference and to become leaders in the Jewish community by continuing Henriettas legacy of Practical Zionism through our work in Israel, our advocacy here in the US, on issues that affect Israel, the Jewishcommunity and health. Henrietta asked the artist of her sculpture to make my eyes look to the future. A most meaningful and purposeful statement.

Boy, I would love to know what Henrietta carried in that black bag of hers, or better yet, what her bag would hold today. I can only imagine that shewasthe one with the tissues to wipe the eyes of the young children as they disembarked the train. Shewould bethe one with the cell phone to reach out to anyone who would listen to her pleas for assistance and for funding to facilitate medical research and care of youth. Shewould bethe one with the small flashlight to bring a big light unto the nations. Over the years I have implored our members to release their inner Henrietta. A woman of purpose and perseverance to emulate for sure.

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A Woman of Purpose and Perseverance - Thrive Global

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What happened

Shares of Aimmune Therapeutics (NASDAQ: AIMT) fell 23.3% in February, according to data provided by S&P Global Market Intelligence, as the launch of its new peanut allergy treatment took time to unfold.

Aimmune rose 40% last year as investors anticipated Palforzia, the firsttreatment approved by the Food and Drug Administration for peanut allergy in children. The regulatory agency approved the treatment on Jan. 31, and now investors are waiting to see how the first weeks of sales progress. The process is taking time because of the risk management procedure involved in the launch.

Image source: Getty Images.

Palforzia, an orally administered powder made of peanut protein, works by desensitizing patients to the allergen. In order to lower risk in case a new patient suffers a reaction to the therapy, the FDA has set up the Risk Evaluation and Mitigation Strategy (REMS) program. Physicians and patients must enroll in REMS and follow guidelines before treatment can begin. This process, along with the FDA's standard procedure of examining and releasing the first batches of biologic product, lengthened the timeline from approval to sales. Aimmune said during its recent earnings call that it expects to record the first Palforzia sales this month.

Getting physicians and patients on board in the next few months will be crucial for Aimmune. DBVTechnologies (NASDAQ: DBVT) is close behind, with an FDA decision on its peanut allergy drug expected in August. Aimmune now has the advantage of being first to market, before rivals enter with competing products. Aimmune is also expecting a decision on Palforzia from the Europeanregulatory agency in the fourth quarter, and said a decision in Switzerland could come in mid-2021.

All of these elements represent catalysts for the shares over the next year or so. If Aimmune can assure its position as market leader, the shares of this biotech company will benefit in the long term.

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Why Aimmune Therapeutics Shares Fell 23.3% in February - Nasdaq

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Newswise Launching no earlier than March 6 at 11:50 PM EST, the Johns Hopkins University will send heart muscle tissues, contained in a specially-designed tissue chip the size of a small cellphone, up to the microgravity environment of the International Space Station (ISS) for one month of observation.

The project, led by Deok-Ho Kim, an Associate Professor of Biomedical Engineering and Medicine at The Johns Hopkins University and the projects principal investigator, will hopefully shed light on the aging process and adult heart health, and facilitate the development of treatments for heart muscle diseases.

Scientists already know that humans exposed to space experience changes similar to accelerated aging, so we hope the results can help us better understand and someday counteract the aging process, says Kim.

The researchers also hope the study will demystify why astronauts in space have reduced heart function and are more prone to serious irregular heartbeat; these results could help protect astronauts hearts on long missions in the future, as well as provide information on how to combat heart disease.

Kim and his team used human induced pluripotent stem cells to grow cardiomyocytes, or heart muscle cells, in a bioengineered, miniaturized tissue chip that mimics the function of the adult human heart. While other researchers have studied stem cell-derived heart muscle cells in space before, these studies relied on cells cultured on 2D surfaces, or flat planes, that arent representative of how cells exist and behave in the body, and are therefore underdeveloped compared to their counterparts in adult humans.

The teams tissue platform gives the advantage of the cells residing in a 3D environment, which will allow for better imitation of how cell signals and actions develop as they would in the human body. This 3D environment is possible thanks to a new scaffold biomaterial, or support structure which holds the tissues together, that accelerates development of the heart muscle cells within. This will allow the scientists to collect data useful for understanding the adult human body. Scientists could someday use this data and platform to develop new drugs, among many other applications.

Using a motion sensor magnet setup, the team will receive real-time measurements of how the tissues on the ISS beat. After about one month in space, the tissues will return to Earth and will be analyzed for any differences in gene expression and contraction caused by the extended stay in microgravity. Some of these tissues will be cultured for an additional week on Earth for the researchers to examine any recovery effects. The team will also have identical heart tissues on Earth at the University of Washington to serve as controls.

We hope that this project will give us meaningful data that we can use to understand the hearts structure and how it functions, so that we can improve the health of both astronauts and those down here on Earth, says Kim.

"The entire team is excited to see the results we get from this experiment. If successful, we will embark on the second phase of the study where tissues will be sent up to the ISS once again in two years, but this time, we will be able to test a variety of drugs to see which ones will best ameliorate the potentially harmful effects of microgravity on cardiac function," says Jonathan Tsui, a postdoctoral fellow in the Department of Biomedical Engineering at The Johns Hopkins University and a member of Kims lab.

This project is funded by the National Center for Advancing Translational Sciences (NCATS) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB) as part of the Tissue Chips in Space initiative in collaboration with the ISS U.S. National Laboratory.

Collaborators on this project include Eun Hyun Ahn of The Johns Hopkins University; Nathan Sniadecki and Alec Smith of The University of Washington; Peter Lee of Ohio State University; and Stefanie Countryman of Bioserve Space Technologies at the University of Colorado Boulder. For space flight the team has worked with BioServe Space Technologies to translate the ground platform into a space flight certified system.

Link:
Little Tissue, Big Mission: Beating Heart Tissues to Ride Aboard The ISS - Newswise

Cardiac Stem Cells Comments Off on Little Tissue, Big Mission: Beating Heart Tissues to Ride Aboard The ISS – Newswise | March 5th, 2020

The success of approved stem cell therapies has caused a surge in interest of biopharma developers in this field; many innovator companies are currently progressing proprietary leads across different phases of clinical development, with cautious optimism

LONDON, March 4, 2020 /PRNewswire/ -- Roots Analysishas announced the addition of "Global Stem Cells Market: Focus on Clinical Therapies, 20202030 (Based on Source (Allogeneic, Autologous); Origin (Adult, Embryonic); Type (Hematopoietic, Mesenchymal, Progenitor); Lineage (Amniotic Fluid, Adipose Tissue, Bone Marrow, Cardiosphere, Chondrocytes, Corneal Tissue, Cord Blood, Dental Pulp, Neural Tissue Placenta, Peripheral Blood, Stromal Cells); and Potency (Multipotent, Pluripotent))" report to its list of offerings.

There is a growing body of evidence supporting the vast applicability and superiority of treatment outcomes of stem cell therapies, compared to conventional treatment options. In fact, the unmet needs within this domain have spurred the establishment of many start-ups in recent years.

To order this 500+ page report, which features 185+ figures and 220+ tables, please visit this link

Key Market Insights

Over 280 stem cell therapies are under development, most of which are allogeneic products

More than 50% of the pipeline candidates are in the mid to late phase trials (phase II and above), and allogenic therapies (majority of which are derived from the bone marrow) make up 65% of the pipeline.

70% of pipeline candidates are based on mesenchymal stem cells

It is worth highlighting that the abovementioned therapies are designed to treat musculoskeletal (22%), neurological (21%) and cardiovascular (15%) disorders. On the other hand, hematopoietic stem cell-based products are mostly being evaluated for the treatment of oncological disorders, primarily hematological malignancies.

Close to 85% stem cell therapy developers are based in North America and Asia-Pacific regions

Within these regions, the US, China, South Korea and Japan, have emerged as key R&D hubs for stem cell therapies. It is worth noting that majority of the initiatives in this domain are driven by small / mid-sized companies

Over 1,500 grants were awarded for stem cell research, since 2015

More than 45% of the total amount was awarded under the R01 mechanism (which supports research projects). The NCI, NHLBI, NICHD, NIDDK, NIGMS and OD emerged as key organizations that have offered financial support for time periods exceeding 25 years as well.

Outsourcing has become indispensable to R&D and manufacturing activity in this domain

Presently, more than 80 industry / non-industry players, based in different regions across the globe, claim to provide contract development and manufacturing services to cater to the unmet needs of therapy developers. Examples include (in alphabetical order) Bio Elpida, Cell and Gene Therapy Catapult, Cell Tech Pharmed, GenCure, KBI Biopharma, Lonza, MEDINET, Nikon CeLL innovation, Roslin Cell Therapies, WuXi Advanced Therapies and YposKesi.

North America and Asia-Pacific markets are anticipated to capture over 80% share by 2030

The stem cell therapies market is anticipated to witness an annualized growth rate of over 30% during the next decade. Interestingly, the market in China / broader Asia-Pacific region is anticipated to grow at a relatively faster rate.

To request a sample copy / brochure of this report, please visit this link

Key Questions Answered

The USD 8.5 billion (by 2030) financial opportunity within the stem cell therapies market has been analyzed across the following segments:

The report features inputs from eminent industry stakeholders, according to whom stem cell therapies are currently considered to be a promising alternatives for the treatment of a myriad of disease indications, with the potential to overcome challenges associated with conventional treatment options. The report includes detailed transcripts of discussions held with the following experts:

The research covers brief profiles of several companies (including those listed below); each profile features an overview of the company, financial information (if available), stem cell therapy portfolio and an informed future outlook.

For additional details, please visit

https://www.rootsanalysis.com/reports/view_document/stem-cells-market/296.htmlor email sales@rootsanalysis.com

You may also be interested in the following titles:

Contact:Gaurav Chaudhary+1(415)800-3415+44(122)391-1091Gaurav.Chaudhary@rootsanalysis.com

Logo: https://mma.prnewswire.com/media/742223/Roots_Analysis_Logo.jpg

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With Over 280 Therapies Under Evaluation, the Stem Cell Therapy Market is Estimated to be Worth USD 8.5 Billion by 2030, Claims Roots Analysis - P&T...

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Regenerative Medicine Market: Snapshot

Regenerative medicine is a part of translational research in the fields of molecular biology and tissue engineering. This type of medicine involves replacing and regenerating human cells, organs, and tissues with the help of specific processes. Doing this may involve a partial or complete reengineering of human cells so that they start to function normally.

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Regenerative medicine also involves the attempts to grow tissues and organs in a laboratory environment, wherein they can be put in a body that cannot heal a particular part. Such implants are mainly preferred to be derived from the patients own tissues and cells, particularly stem cells. Looking at the promising nature of stem cells to heal and regenerative various parts of the body, this field is certainly expected to see a bright future. Doing this can help avoid opting for organ donation, thus saving costs. Some healthcare centers might showcase a shortage of organ donations, and this is where tissues regenerated using patients own cells are highly helpful.

There are several source materials from which regeneration can be facilitated. Extracellular matrix materials are commonly used source substances all over the globe. They are mainly used for reconstructive surgery, chronic wound healing, and orthopedic surgeries. In recent times, these materials have also been used in heart surgeries, specifically aimed at repairing damaged portions.

Cells derived from the umbilical cord also have the potential to be used as source material for bringing about regeneration in a patient. A vast research has also been conducted in this context. Treatment of diabetes, organ failure, and other chronic diseases is highly possible by using cord blood cells. Apart from these cells, Whartons jelly and cord lining have also been shortlisted as possible sources for mesenchymal stem cells. Extensive research has conducted to study how these cells can be used to treat lung diseases, lung injury, leukemia, liver diseases, diabetes, and immunity-based disorders, among others.

Global Regenerative Medicine Market: Overview

The global market for regenerative medicine market is expected to grow at a significant pace throughout the forecast period. The rising preference of patients for personalized medicines and the advancements in technology are estimated to accelerate the growth of the global regenerative medicine market in the next few years. As a result, this market is likely to witness a healthy growth and attract a large number of players in the next few years. The development of novel regenerative medicine is estimated to benefit the key players and supplement the markets growth in the near future.

Global Regenerative Medicine Market: Key Trends

The rising prevalence of chronic diseases and the rising focus on cell therapy products are the key factors that are estimated to fuel the growth of the global regenerative medicine market in the next few years. In addition, the increasing funding by government bodies and development of new and innovative products are anticipated to supplement the growth of the overall market in the next few years.

On the flip side, the ethical challenges in the stem cell research are likely to restrict the growth of the global regenerative medicine market throughout the forecast period. In addition, the stringent regulatory rules and regulations are predicted to impact the approvals of new products, thus hampering the growth of the overall market in the near future.

Global Regenerative Medicine Market: Market Potential

The growing demand for organ transplantation across the globe is anticipated to boost the demand for regenerative medicines in the next few years. In addition, the rapid growth in the geriatric population and the significant rise in the global healthcare expenditure is predicted to encourage the growth of the market. The presence of a strong pipeline is likely to contribute towards the markets growth in the near future.

Global Regenerative Medicine Market: Regional Outlook

In the past few years, North America led the global regenerative medicine market and is likely to remain in the topmost position throughout the forecast period. This region is expected to account for a massive share of the global market, owing to the rising prevalence of cancer, cardiac diseases, and autoimmunity. In addition, the rising demand for regenerative medicines from the U.S. and the rising government funding are some of the other key aspects that are likely to fuel the growth of the North America market in the near future.

Furthermore, Asia Pacific is expected to register a substantial growth rate in the next few years. The high growth of this region can be attributed to the availability of funding for research and the development of research centers. In addition, the increasing contribution from India, China, and Japan is likely to supplement the growth of the market in the near future.

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Global Regenerative Medicine Market: Competitive Analysis

The global market for regenerative medicines is extremely fragmented and competitive in nature, thanks to the presence of a large number of players operating in it. In order to gain a competitive edge in the global market, the key players in the market are focusing on technological developments and research and development activities. In addition, the rising number of mergers and acquisitions and collaborations is likely to benefit the prominent players in the market and encourage the overall growth in the next few years.

Some of the key players operating in the regenerative medicine market across the globe areVericel Corporation, Japan Tissue Engineering Co., Ltd., Stryker Corporation, Acelity L.P. Inc. (KCI Licensing), Organogenesis Inc., Medtronic PLC, Cook Biotech Incorporated, Osiris Therapeutics, Inc., Integra Lifesciences Corporation, and Nuvasive, Inc.A large number of players are anticipated to enter the global market throughout the forecast period.

About TMR Research:

TMR Research is a premier provider of customized market research and consulting services to business entities keen on succeeding in todays supercharged economic climate. Armed with an experienced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

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Regenerative Medicine Market Analysis Growth Demand, Key Players, Share Size, and Forecast To 2025 - Monroe Scoop

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4-Mar-2020

Ingredients | Skin Care

inspira: cosmetics produces and markets high-quality, contemporary cosmetic products for individual skin care worldwide

The German company is based in Aachen and was founded in 2000. The development of outstanding and highly effective products with excellent compatibility is a matter of course for inspira: cosmetics.

The products visibly improve the appearance of the skin and let the user look in the best possible way for his/her respective age.

Now Volker Kloubert, Managing Partner of inspira: cosmetics proudly announced: "We are more than happy and feel very honoured that 3 of our entries are finalists in the Pure Beauty Global Awards and we are looking forward to the award ceremony in May in Amsterdam. Lets keep fingers crossed!

The finalist products from inspira: cosmetics reflect the broad scope of cosmetics the brand is covering.

The male scent 4MEN ONLY is nominated in the category Best Male Fragrance. A masculine composition of oriental notes, combined with woods and musk. Adventurous and very sexy! For men only. The sophisticated fragrance was created by master perfumers in Grasse/France.

Finalist in the category Best Lip Product is the Volumizing Lip Remedy, a lip care stick in stylish silver metal packaging with high quality active ingredients like hyaluronic acid, shea butter, coconut oil, spearmint oil for a fresh taste and the Peptide Complex VOLULIP than can increase the lip volume by up to 82% in 4 weeks as it stimulates the production of hyaluronic acid in the lips.

Very important: NO burning sensation, the product is smooth as silk.

Age Reboot Serum is the new holistic anti aging serum in the inspira: med range using state of the art active ingredients to protect and rejuvenate the skin.

Phyto stem cells help the skin to adapt to changing environmental conditions like heat or cold and protect the cells whereas three different hyaluronic acids smooth the skin, even out wrinkles and EGF (Epidermal Growth Factor) stimulates cell renewal.

In clinical studies the skin was rejuvenated by up to 10 years in four weeks of regular use.

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Three of inspira: cosmetics entries are finalists in the Pure Beauty Global Awards 2020 - Cosmetics Business

Skin Stem Cells Comments Off on Three of inspira: cosmetics entries are finalists in the Pure Beauty Global Awards 2020 – Cosmetics Business | March 4th, 2020

FORMS of blood cancer, such as leukaemia or lymphoma, are the fifth most common cancer, and the third biggest cause of cancer deaths.

Yet warning signs can be so unlike those of other cancers, that its often diagnosed at a very late stage.

Research by UK blood cancer charity Bloodwise (bloodwise.org.uk) found more than a third of sufferers had to visit their GP three or more times with symptoms before being a hospital referral. This makes it the worst performing cancer in terms of early diagnosis.

Why is it so difficult to spot? Blood cancers, which stop blood stem cells from working normally and can make you weak and prone to infections, have three main types with many different variations. These variations have numerous diverse symptoms, which can often be mistaken for other less serious conditions.

Not all signs of blood cancer are easily identifiable, or are associated with typical symptoms of cancer, such as a lump or abnormal mole, says haematologist Dr Manos Nikolousis, a medical consultant with UK blood cancer charity DKMS.

Blood cancer often presents in ways which are most commonly associated with unrelated and less serious illnesses, like a cold or flu. In other circumstances, patients notice a change in their body which they cant quite put their finger on.

One of the treatments for blood cancer is a stem cell transplant that restores blood-forming stem cells in patients whove had theirs destroyed by very high doses of chemotherapy and/or radiotherapy. But Nikolousis points out that only one in three blood cancer patients who need a transplant find a matching blood stem cell donor in their family. The remaining two-thirds have to rely on an unrelated donor, which significantly reduces their chance of finding a crucial match.

Here, Nikolousis outlines some blood cancer symptoms and warning signs...

Musculoskeletal pain in muscles, joints, tendons, bones or structures that support the limbs, neck or back.

One of the most common symptoms associated with blood cancer. The frequency and lasting impact of bruising can be a key warning sign, so its important to book an appointment with your GP if this develops.

Unexplained and persistent tiredness is one of the biggest tell-tale signs of blood cancer. People who have cancer-related fatigue find it incredibly challenging to complete simple tasks that we tend to take for granted.

The lymph nodes are small lumps of tissue that contain white blood cells. When inflamed, they can be felt as lumps under the skin; most commonly in the neck, armpit or groin area.

There may be new headaches that feel different. Theyre likely to occur frequently and be severe and long-lasting.

Persistent abdominal discomfort, presenting as a sharp pain or a sense of feeling full.

This can be described as a feeling of pins and needles/numbness that moves up to the legs, or from fingers to the arms.

This can feel like a fluttering, a sudden thump or a fast pounding sensation in the chest. It can also be felt in the neck or ear when lying down.

People may describe this as feeling mentally drained or dizzy.

Blood cancer patients may have continuous trouble falling asleep or staying asleep.

Persistent and irritable, this may be experienced all over the body, or in isolated spots.

These symptoms are common and dont automatically mean you have cancer. But if you notice any unusual or ongoing changes, its always best to see your doctor and get checked.

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Eleven symptoms of blood cancer that everybody needs to know about... - Echo Live

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Results Surpass FDA-Agreed Efficacy Threshold

Omeros Corporation (Nasdaq: OMER) today reports an update on clinical data from its pivotal trial of narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), markedly exceeding the FDA-agreed threshold for the primary efficacy endpoint. While an overview of preliminary data submitted to FDA was made public on December 4, 2019 in a press release from the company, all patients have now completed treatment and trial enrollment has been closed. Narsoplimab is Omeros human monoclonal antibody targeting mannan-binding lectin-associated serine protease 2 (MASP-2).

In recent meetings with FDA focused on clinical as well as chemistry, manufacturing and controls (CMC) data, FDA confirmed important aspects of Omeros rolling Biologics License Application (BLA) for narsoplimab in HSCT-TMA. The BLA continues on its clear path to completion.

The efficacy threshold agreed with FDA, the updated results from the 28-patient trial, and highlights of the recent FDA meetings are the following:

Primary Endpoint

15% is the FDA-agreed efficacy threshold for the primary endpoint (i.e., the complete response rate [CRR]) in the clinical trial

The CRR for the study population, and the lower limit of the 95 percent confidence interval (95% CI), significantly exceed the efficacy threshold:

54 percent CRR (95% CI = 34 percent to 72 percent, p-value < 0.0001) in patients who received at least one dose of narsoplimab

65 percent CRR (95% CI = 43 percent to 84, p-value < 0.0001) in patients who received the protocol-specified narsoplimab treatment of at least 4 weeks of dosing

As described in the December 4, 2019 press release, the FDA-agreed primary endpoint (the CRR) is the proportion of patients who fully achieve a rigorous set of response criteria, requiring both improvement in HSCT-TMA laboratory markers (platelet count and lactate dehydrogenase [LDH] levels) and improvement in clinical status comprised of organ (renal, pulmonary, gastrointestinal and neurological) function and transfusions (platelet and red blood cells). The full response criteria are provided below.

Secondary Endpoints

Story continues

The 100-day survival (defined as survival from the day of HSCT-TMA diagnosis) is 68 percent in all treated patients, 83 percent in patients who received at least 4 weeks of narsoplimab treatment as specified by the protocol, and 93 percent in patients who responded to narsoplimab treatment. Experts familiar with the pivotal trial data would expect a 100-day survival rate of less than 20 percent in the trial population.

Preliminary results of the laboratory secondary efficacy endpoints (change from pre-treatment baseline for each laboratory value) continue to demonstrate meaningful improvement and meet statistical significance in platelet count, LDH and haptoglobin (p < 0.01 in all treated patients).

Safety

The most commonly reported adverse events in the trial were diarrhea, nausea, vomiting, hypokalemia, neutropenia and fever all common in stem-cell transplant patients.

Six deaths occurred during the trial. These were due to sepsis, progression of the underlying disease, and graft-versus-host disease, all common causes of death in this patient population.

The treated population had multiple high-risk features that portend a poor outcome, including the persistence of HSCT-TMA despite modification of immunosuppression (which was a criterion for entry into the trial), graft-versus-host disease, significant infections, non-infectious pulmonary complications and neurological findings. Patients in the trial had a high expected mortality rate, with 93% of them having multiple risk factors.

"The efficacy and safety data from the pivotal trial with narsoplimab are encouraging," said Miguel-Angel Perales, M.D., Deputy Chief of the Adult Bone Marrow Transplantation Service and Director of the Adult Stem Cell Transplantation Fellowship at Memorial Sloan Kettering Cancer Center. "Given the trials stringent response criteria across laboratory markers and organ function, the complete response rate seen with narsoplimab is remarkable, as is the 100-day survival. There currently is no approved treatment for HSCT-TMA. Current therapy is generally limited to supportive care and withdrawal of drugs critical for GVHD prophylaxis. Not only could narsoplimab become central to the treatment of HSCT-TMA, it might well allow us to maintain that needed GVHD prophylaxis."

Complete clinical trial data will be presented by Dr. Perales later this month at the Annual Meeting of the European Society for Blood and Marrow Transplantation in Madrid.

Recent FDA Meeting Highlights and CMC Updates

FDA confirmed that the number of HSCT-TMA patients enrolled is sufficient for the BLAs filing and review for approval. FDA agreed to stopping enrollment.

FDA requested near-term manufacturing dates for narsoplimab so that FDAs pre-approval inspections could be scheduled.

FDA and Omeros reached agreement on CMC requirements for stability data and release assays.

Omeros elected to accelerate the manufacturing schedule for a one-time set of five narsoplimab process validation and commercial lots. These lots were successfully manufactured by Omeros manufacturing partner Lonza, satisfy the BLA requirements and can be used for commercial sale following approval.

"The non clinical sections of our BLA have been submitted, our CMC campaign is progressing well with process validation and commercial lots already manufactured, and our pivotal trial is complete," stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "The efficacy threshold agreed with FDA reflects both the primary endpoints stringent response criteria and the poor outcomes expected in the patients enrolled in our trial. Of course, were very pleased that the response rates and confidence intervals seen with narsoplimab are well above that efficacy threshold. We look forward to continuing to work closely with regulators to make the drug commercially available to transplanters and their patients in the U.S. and internationally as quickly as possible."

In addition to its HSCT-TMA program, Omeros is enrolling its narsoplimab Phase 3 clinical trials for immunoglobulin A (IgA) nephropathy and atypical hemolytic uremic syndrome (aHUS). Narsoplimab has been granted, for both HSCT-TMA and IgA nephropathy, FDAs breakthrough therapy designation as well as orphan drug designations from FDA and the European Medicines Agency. The drug also holds FDAs fast-track designation for aHUS.

Primary Efficacy Endpoint

To be considered a responder, a patient must achieve the primary endpoint of complete HSCT-TMA response defined by improvement in laboratory markers and improvement in clinical status.

Laboratory Markers

Criteria for improvement in laboratory markers are LDH less than 1.5 x upper limit of normal AND improvement of platelet count measures:

For patients with baseline platelet count 20,000/L, response requires tripling over baseline platelet count, a post-baseline platelet count >30,000/L, and freedom from platelet transfusion

For patients with baseline platelet count >20,000/ L, response requires: an increase in platelet count by 50%, a post-baseline platelet count >75,000 /L, and freedom from platelet transfusion

Clinical Status

Criteria for improvement in clinical status requires at least one of the following:

Renal response requires >40% reduction in creatinine, or normalization of creatinine and >20% reduction in creatinine, or discontinuation of renal replacement therapy

Pulmonary response requires extubation and discontinuation of ventilator support, or discontinuation of non-invasive mechanical ventilation (continuous positive pressure ventilation)

Gastrointestinal response applicable only to patients with biopsy-proven gastrointestinal HSCT-TMA and requires improvement in gastrointestinal function as determined by the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria

Neurological response requires improvement in reversible neurological conditions (e.g., cessation of seizures), or stabilization of irreversible neurological conditions (e.g., stability of neurological deficits following stroke without further deterioration or subsequent strokes)

Freedom from transfusion only applicable if patient was undergoing transfusion at baseline

About Omeros Corporation

Omeros is an innovative biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting complement-mediated diseases, disorders of the central nervous system and immune-related diseases, including cancers. In addition to its commercial product OMIDRIA (phenylephrine and ketorolac intraocular solution) 1%/0.3%, Omeros has multiple Phase 3 and Phase 2 clinical-stage development programs focused on complement-mediated disorders and substance abuse. In addition, the company has a diverse group of preclinical programs including GPR174, a novel target in immuno-oncology that modulates a new cancer immunity axis recently discovered by Omeros. Small-molecule inhibitors of GPR174 are part of Omeros proprietary G protein-coupled receptor (GPCR) platform through which it controls 54 new GPCR drug targets and their corresponding compounds. The company also exclusively possesses a novel antibody-generating platform.

About HSCT-TMA

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a significant and often lethal complication of stem cell transplants. This condition is a systemic, multifactorial disorder caused by endothelial cell damage induced by conditioning regimens, immunosuppressant therapies, infection, GvHD, and other factors associated with stem cell transplantation. Endothelial damage, which activates the lectin pathway of complement, plays a central role in the development of HSCT-TMA. The condition occurs in both autologous and allogeneic transplants but is more common in the allogeneic population. In the United States and Europe, approximately 25,000 to 30,000 allogeneic transplants are performed annually. Recent reports in both adult and pediatric allogeneic stem cell transplant populations have found an HSCT-TMA incidence of approximately 40 percent, and high-risk features may be present in up to 80 percent of these patients. In severe cases of HSCT-TMA, mortality can exceed 90 percent and, even in those who survive, long-term renal sequalae are common. There is no approved therapy or standard of care for HSCT-TMA.

About Narsoplimab

Narsoplimab, also known as "OMS721," is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a novel pro-inflammatory protein target and the effector enzyme of the lectin pathway of complement. Importantly, inhibition of MASP-2 does not appear to interfere with the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection. Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2.

Phase 3 clinical programs are in progress for narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), in immunoglobulin A (IgA) nephropathy, and in atypical hemolytic uremic syndrome (aHUS). The FDA has granted narsoplimab breakthrough therapy designations for HSCT-TMA and for IgA nephropathy; orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies, for the treatment of HSCT-TMA and for the treatment of IgA nephropathy; and fast track designation for the treatment of patients with aHUS. The European Medicines Agency has granted orphan drug designation to narsoplimab for treatment in HSCT and for treatment of primary IgA nephropathy.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, which are subject to the "safe harbor" created by those sections for such statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "can," "could," "estimate," "expect," "goal," "intend," "likely", "look forward to," "may," "on track," "plan," "potential," "predict," "project," "prospects," "scheduled," "should," "slated," "targeting," "will," "would" and similar expressions and variations thereof. Forward-looking statements, including statements regarding anticipated regulatory submissions, expectations regarding regulatory exclusivities, the timing and results of ongoing or anticipated clinical trials, and the therapeutic application of Omeros investigational product, are based on managements beliefs and assumptions and on information available to management only as of the date of this press release. Omeros actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, availability and timing of data from clinical trials and the results of such trials, unproven preclinical and clinical development activities, regulatory oversight, intellectual property claims, competitive developments, litigation, and the risks, uncertainties and other factors described under the heading "Risk Factors" in the companys Annual Report on Form 10-K for the year ended December 31, 2019, filed with the Securities and Exchange Commission on March 2, 2020. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and the company assumes no obligation to update these forward-looking statements, whether as a result of any new information, future events or otherwise, except as required by applicable law.

Dr. Miguel-Angel Perales has received compensation from Omeros for advisory services.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200302005938/en/

Contacts

Jennifer Cook WilliamsCook Williams Communications, Inc.Investor and Media Relations360.668.3701jennifer@cwcomm.org

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Omeros Corporation Reports Updated Results from Narsoplimab HSCT-TMA Clinical Trial and Highlights from Recent Clinical and CMC Meetings with FDA -...

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A wave of new targeted therapies expands the options in acute myeloid leukemia.

As a mother of three, I dont focus on myself a lot, says Hibbard, who lives in Yorba Linda, California, and was then 37. I was having a lot of bone pain in Vegas, but I have scoliosis, so I always have some pain. Everything just multiplied when I got back home.

She rushed to schedule a same-day appointment with her doctor. As someone in the medical field she works as an ultrasound technician Hibbard had no hesitation about learning what could be wrong. Her doctor appeared alarmed about how sick she looked and immediately ordered bloodwork.

Her platelet count was astoundingly low. A normal count ranges from 150,000 to 450,000 platelets per microliter of blood; Hibbards hovered around 20,000. She initially assumed something had gone wrong with her intrauterine device, because she had recently experienced heavy vaginal bleeding abnormal uterine bleeding can be a symptom of certain hematologic cancers.

I thought I was anemic because I had lost a lot of blood. Cancer didnt even cross my mind until the doctor came in and told me I had leukemia, she says.

A week and half after returning from her vacation, Hibbard received a diagnosis of acute myeloid leukemia (AML). This cancer of the blood and bone marrow affects more than 20,000 people each year in the United States.

For years, prognosis remained poor for patients with the disease, which has a 24% five-year survival rate for people ages 20 and older and 67% for those younger than 20, with limited treatment options. But the past two years brought an explosion of new medications approved by the Food and Drug Administration (FDA) to treat AML, particularly therapies targeting specific genomic mutations that may confer a worse prognosis.

For more than 45 years, the treatment for AML only involved intensive chemotherapy, and that was the only chance at a cure, says Amer Zeidan, an associate professor of internal medicine at Yale Cancer Center in New Haven, Connecticut. But since 2017, weve had a revolution in the treatment of AML after many years of no approved agents. I give an analogy in (terms) of before Christ and after Christ because the landscape has changed so much.

WHAT DOES AN AML DIAGNOSIS MEAN?

Historically, chemotherapy for the treatment of AML involves two phases: induction therapy followed by consolidation therapy. Shortly after diagnosis, a patient will undergo induction therapy to rid the body of any signs of the disease.

Most often, patients receive the combination of cytarabine and an anthracycline drug such as Cerubidine (daunorubicin) or Idamycin (idarubicin). Approximately 75% of younger adults with AML and 50% of patients older than 60 achieve complete remission, or disappearance of overt leukemia in the bone marrow, after induction treatment. Once a patient has recovered, consolidation therapy, chemotherapy or a stem cell transplant kills any remaining leukemia cells.

Early signs of AML, which is typically associated with older age (more than 65 years), history of tobacco smoking and certain inherited genetic disorders, include weight loss, fatigue, fever, night sweats, bruising and excessive bleeding. Because AML is generally widespread throughout the bone marrow and possibly other organs, it is not staged like other cancers. About half of patients who achieve remission after initial treatment will relapse.

Genomic testing revealed that Hibbard had a FLT3 mutation. The most common mutation in AML, FLT3 is found in 30% of all cases and associated with a particularly aggressive form of the disease and a higher risk of relapse. My oncologist told me, Bad news you have the FLT3 mutation. But the good news is that they just developed an inhibitor you can take, recalls Hibbard. He said it with a big smile on his face.

In April 2017, the FDA approved Rydapt (midostaurin), the first targeted therapy for AML, combined with chemotherapy to treat adults with a new diagnosis and a FLT3 mutation. The oral medication belongs to a group of drugs called FLT3 inhibitors, which block several enzymes that promote cell growth.

During Hibbards month in the hospital to receive induction chemotherapy, she experienced several life-threatening complications, including a blood clotting disorder, two strokes and a bout of sepsis. Believing she was on her deathbed; she made a video saying goodbye to her children.

Hibbard recovered, returned home and began treatment with Rydapt, which made her nauseated. The drugs other common side effects include low levels of white blood cells with fever (febrile neutropenia), inflammation of the mucous membranes and vomiting.

Hibbard achieved remission following more chemotherapy and a stem cell transplant and remains free of cancer. I was extremely excited about taking Rydapt because I felt truly blessed that there was an inhibitor for my mutation, since it was so aggressive, says Hibbard, who is now 39.

It smells horrible, and its a large pill, but I took it willingly because I knew it would improve my chances of survival.

RIGHT ON TARGET

Rydapt is one of eight drugs for AML that have gained FDA approval since 2017. Xospata (gilteritinib), another type of targeted therapy that inhibits FLT3, was approved in May2019 for adults who stopped responding to treatment or whose disease had relapsed.

The IDH inhibitors Idhifa (enasidenib) and Tibsovo (ivosidenib) target mutations in the IDH1 and IDH2 genes. Daurismo (glasdegib), Venclexta (venetoclax) and Vyxeos (CPX-351) expand the options for older patients who cant be treated with intensive chemotherapy because of its toxicities. Mylotarg (gemtuzumab ozogamicin) can be given to patients who express the CD33 antigen.

We now have a better understanding of the biology behind AML, especially the molecular mutations that drive this disease, and we have developed treatment that targets these mutations, says Dr. Kevin Kelly, an associate professor of clinical medicine at the University of Southern California in Los Angeles. One of the most important mutations is FLT3, targeted by midostaurin and gilteritinib. These drugs specifically target the leukemia cells while being less toxic on the normal tissue of the body.In a large clinical trial, patients with new diagnoses who took Rydapt along with chemotherapy lived longer than those who received chemotherapy alone. After four years, 51.4% in the Rydapt group were still alive compared with 44.3% in the chemotherapy group.

Findings from the ADMIRAL trial showed that Xospata similarly extended survival. Patients who took the FLT3 inhibitor alone had a median overall survival of 9.3 months compared with 5.6 months for those given chemotherapy alone. Though encouraging, these are early findings from new files, and long-term follow-up could bring significantly different results, cautioned experts.

Side effects of Xospata include nausea, vomiting, diarrhea, constipation, pain or sores in the mouth or throat, shortness of breath, muscle or joint pain and dizziness. The drug can also cause differentiation syndrome, a potentially fatal complication believedto be caused by release of cytokines from leukemia cells. It can be treated with steroids, but prompt recognition is key. Symptoms include fever, cough, trouble breathing, bone pain, rapid weight gain and swelling in the arms, legs, underarm, groin or neck.Differentiation syndrome is also a concern for patients treated with Idhifa and Tibsovo. Based on clinical trial results showing that 19% of patients had complete remission for a median of 8.2 months, Idhifa was approved in August 2017 for patients who relapsed or became resistant to treatment for AML. The targeted therapy homes in on mutations in the IDH2 gene, which are found in 8%-19% of patients with AML.

In July 2018, Tibsovo, which targets IDH1 mutations found in 7%-14% of patients with AML, was approved. Roughly two years later, the FDA allowed the drugs use as a first-line treatment for patients who arent eligible for intensive chemotherapy.Another type of targeted therapy, Mylotarg aims at AML cells expressing the CD33 antigen, found in more than 80% of patients. Reapproved by the FDA in September 2017 to treat patients with new diagnoses and those who relapsed or became resistant to therapy, the agent combines the unique targeting of a monoclonal antibody with the cancer-killing ability of a chemotherapy drug.

What is happening now in AML is similar to what already happened with multiple myeloma. Today, proteasome inhibitors and other biological drugs have almost completely replaced chemotherapy for almost all ages and subsets of myeloma, says Dr. Naval Daver, an associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center in Houston. With these new targeted therapies, we can improve outcome and survival in AML while reducing the need for chemotherapy and even stem cell transplants.

OPTIONS FOR OLDER PATIENTS

The lack of treatment options for older patients with AML only about half of patients older than 60 receive intensive induction chemotherapy; the rest get either gentler chemotherapy that doesnt aim to cure or supportive care without any chemotherapy has meant that many are undertreated, with poorer clinical outcomes.

Fortunately, the approvals of Venclexta and Daurismo for patients aged 75 and older bring new options. Venclexta, which blocks BCL-2 proteins, was granted accelerated approved by the FDA based on promising results from early-phase clinical trials, but two larger, ongoing studies are examining its effectiveness and safety. The rate of complete remission was up to 54% for Venclexta plus decitabine but varied depending on which chemotherapy drug was given.

There has been dramatic progress in the treatment of AML in recent years, with one of the most important drugs being venetoclax for older AML populations, who have been one of the most difficult populations to treat, Daver says. It works synergistically with low-dose chemotherapy drugs already being used, which is a major breakthrough in the treatment of older patients with AML.

Daurismo targets the smoothened, or SMO, protein that fuels the growth and spread of AML. In a clinical trial, the median overall survival in older patients who received Daurismo along with chemotherapy was 8.3 months compared with 4.3 months for those who got chemotherapy alone.

Vyxeos (CPX-351) can also be used in older patients. It's August 2017 approval was for patients with two types of prognoses: newly diagnosed therapy-related AML, which occurs as a complication of cancer treatment in 8%-10% of patients within five years after chemotherapy or radiation, and AML with myelodysplasia-related changes, characterized by a history of certain blood disorders and other significant mutations within cancer cells. Patients with these types of AML tend to be older and have additional medical issues.

A study that compared Vyxeos with traditional chemotherapy showed that patients with new diagnoses who took Vyxeos lived longer, with a median overall survival of 9.56 months compared with 5.95 months, respectively.

In addition, an investigational oral therapy, CC-486, has shown a survival benefit in patients with newly diagnosed AML in the maintenance setting. In a phase 3 trial, researchers saw that the drug extended overall survival by 9.9 months compared with placebo.

We have new drugs available for subsets of the disease, which is why the management of AML is becoming more like personalized medicine, Zeidan says. I think we are going in the direction of more targeted therapy, lower toxicity agents, combinations of different oral agents and, hopefully, incremental improvement in outcomes. Im very optimistic about where the field is going.

The wealth of drug approvals certainly gives more hope to patients with AML, especially those with a previously poor prognosis and lack of treatment options. Rapid genetic testing is leading to the early classification of disease subtypes, pushing AML treatment into the realm of precision medicine. Several clinical trials in progress aim to test combinations of the newer agents, such as Venclexta with an IDH inhibitor.

Hibbard remains thankful for the targeted therapy she received. She believes that the trust she had in the newly approved Rydapt and the entire treatment process helped save her life.

I remember being terrified, with people praying over my bedside. But Im very pragmatic, so I was very much like, OK, now what do we do? Whats the next step? Hibbard says. That was my entire battle. Today I am more than a year post-transplant and grateful to kiss my kids goodnight every night.

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2020 is already promising to be a fantastic year for space exploration. The next generation of Artemis explorers can begin applying for the program that will be journeying to the Moon, Mars and beyond; the James Webb Space Telescope is ready to test key deployments made in space, and even the Orion spacecraft that will blast off to the Moon during Artemis missions has successfully passed its final tests. Furthermore, NASA and commercial space companies prepare for the colonization of orbit, rockets are taking payloads to the International Space Station (ISS) very often and 3D bioprinting is becoming an attractive and useful method to carry out experiments. The next one up is SpaceX mission CRS-20. Scheduled to launch at 11:50 PM Eastern Time (EST) on March 6 from Floridas Cape Canaveral Air Force Station, the unpiloted cargo spacecraft is expected to arrive at the orbiting laboratory two days later with three Techshot-managed research campaigns.

The Indiana-based commercial research company is sending equipment and samples supporting plant, heart and cartilage research for NASA, Emory University and the Uniformed Services University of the Health Sciences (USU) to the ISS. According to the company, astronauts onboard the station will use Techshots 3D BioFabrication Facility (BFF) mounted inside the ISS U.S. National Laboratory (ISS National Lab) since last summer to manufacture human knee menisci for the 4-Dimensional Bioprinting, Biofabrication, and Biomanufacturing, or 4D Bio3program. Based at USU, 4D Bio3 is a collaboration between the USU and The Geneva Foundation, a non-profit organization that advances military medical research.

Funded by the U.S. Defense Health Program and managed by the Geneva Foundation, 4D Bio3promotes the development and application of advanced bioprinting, biofabrication, and biomanufacturing technologies for research pursuant to U.S. Department of Defense priorities and ultimately for translation to clinical medical defense care and training solutions.

This is our most diverse manifest to date, said Techshot President and CEO, John Vellinger. Throughout March well be conducting three major investigations in space for three customers using three very different Techshot-built research devices. Its going to be a busy month, but were excited to see the results.

Techshot owns BFF and the company built it at a cost of approximately seven million dollars. The starting point was an nScrypt printer, which now is highly modified by Techshot for use inside the ISS. In that relationship, Techshot handles all the space bioprinting, while nScrypt handles all the Earth-based bioprinting.

This first experiment for 4D Bio3 next month will be used as a test of the materials and the processes required to print a meniscus in space. Techshot engineers will upload a design file to BFF from the companys Payload Operations Control Center in Greenville, Indiana, and evaluate its success via real-time video from inside the unit. A second meniscus print will take place in BFF early next year and the item will then be returned to Earth for extensive testing and comparison to the nScrypt Earth-printed items. Last year nScrypt printed the same thing at a U.S. military base in Africa with their own printer.

Vincent B.Ho, Director of 4D Bio3 and professor and chair of radiology at USU said that meniscal injuries are one of the most commonly treated orthopedic injuries, and have a much higher incidence in military service membersreported to be almost 10 times that of the civilian population. We successfully biofabricated 3D human medial and lateral menisci in a pilot study performed in Africa last summer and anticipate learning valuable lessons on the challenges and benefits of biofabrication in microgravity by performing a similar experiment on the space station.

Besides BFF, there are four other Techshot owned and operated research machines inside the ISS today. Only the BFF is a bioprinter. The others are an X-ray machine for mice, two identical units called the Techshot Multi-use Variable-gravity Platform (MVP), and one called the ADvanced Space Experiment Processor (ADSEP), which is where cells printed in the BFF go to become conditioned and cultured into the tissue. The company has agreements with NASA and the ISS National Lab that permit Techshot to operate a commercial business in space. This is part of NASAs objective to make orbit more commercial, providing access to space for nearly anyone.

Another complex Techshot-managed experiment launching onboard SpaceX CRS-20 will test whether a heart-specific stem cell, called a cardiac progenitor, multiplies better in space and if more of them become heart muscle cells known as cardiomyocytes. This is part of Chunhui Xu, an associate professor in the department of pediatrics at the Emory University School of Medicine who studies heart cells, research that aims to improve treatments for congenital heart disorders and better the hearts ability to regenerate after injuries.

Preparing the experiments: under the vent hood, Biomedical Engineer Jordan Fite adds media to bags and fluid loops that will be used in the experiment in space (Image: Techshot)

Techshot explained that human cardiac tissues cant repair themselves once damaged from disease, due to this, repairing a failing heart by cell therapy requires a large number of cardiomyocytes, which can be converted from stem cells cultured in two dimensions in Earth-based laboratories. Without the pull of gravity, it is expected that culturing in three dimensions in space, inside specialized Techshot cell culture experiment modules, will increase the yield of high-quality heart muscle cells. The company expects that learning more about why this happens could lead to new strategies for reproducing the same results on a much larger scale on Earth, lowering costs and enabling more patients to receive needed cardiac cell therapies.

Astronaut handling Techshots BFF (Image: Techshot/NASA)

It is expected that once the cargo spacecraft reaches the station, the 12 Techshot experiment modules will be removed from the spacecraft and inserted by the crew into the companys Multi-use Variable-gravity Platform (MVP) unit number two mounted in the Japanese space laboratory known as Kibo.

We are thankful for Techshots engineers who designed the Multi-use Variable-gravity Platform hardware and will help us maintain constant communication with the astronauts during the flight operation. Their professionalism and collaboration with our team have contributed tremendously toward our overall research efforts, said Ho.

Besides the materials for the BFF meniscus print, SpaceX CRS-20 will also carry 12 Passive Orbital Nutrient Delivery System, or PONDS, plant growth devices that Techshot co-developed with Tupperware Brands, and that was first prototyped by NASA Kennedy Space Center. According to company officials, they will be growing red romaine lettuce inthe devices, installed inside two of the space stations identical plant growth chambers each called Veggie. The PONDS units are being tested in two different configurations, each representing approaches refined from two previous flight tests. For this demonstration, lettuce is expected to grow in space for 21 days. Besides the hardware built and own, Techshot also manages the space stations most complex greenhouse, called the Advanced Plant Habitat, and it manages two on-orbit research furnaces called PFMI and SUBSA.

Techshot has been working hard to get samples ready in a lab at the Space Station Processing Facility at NASAs Kennedy Space Center.

Product assurance associate Keri Roeder, program manager Nathan Thomas and mechanical engineer Grant Vellinger prepared samples for Techshot customer Emory University (Image: Techshot)

Founded more than 30 years ago, Techshot operates its own commercial research equipment in space and serves as the manager of three NASA-owned ISS payloads. The company is also working on other space 3D printing technologies. Last fall they tested a laser-based 3D metal printer in zero gravity inside an aircraft performing parabolic arcs over the Gulf of Mexico (sometimes unofficially nicknamed the vomit comet). However, officials suggest that this technology is still at least a couple of years from Techshot launching it to the space station.

NASA and dozens of companies continue to work together to develop the means for astronauts and space explorers to endure life in orbit, the Moon and other planets. This vision is enthralling for anyone who ever dreamed of going to space, even hopeful of the next generations that will be able to experience space travel and conduct research work in microgravity. Perhaps we are too hopeful of the future, but with so much going on, its difficult not to be.

The launch on Friday will be the last SpaceX launch under the current NASA CRS-1 contract, yet SpaceX will continue performing resupply missions under a new CRS-2 contract beginning with the next scheduled resupply mission in August this year. To watch the launch, which is scheduled to take place at 11:50 p.m. EST on Friday, March 6, and capture of the spacecrafts arrival at the ISS, you can tune into NASA TV using the video below:

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Techshots New Projects Will be on the Next SpaceX Mission Launch - 3DPrint.com

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A synopsis of the global canine stem cell therapy market with reference to the global healthcare pharmaceutical industry

Despite the economic and political uncertainty in the recent past, the global healthcare industry has been receiving positive nudges from reformative and technological disruptions in medical devices, pharmaceuticals and biotech, in-vitro diagnostics, and medical imaging. Key markets across the world are facing a massive rise in demand for critical care services that are pushing global healthcare spending levels to unimaginable limits.

A rapidly multiplying geriatric population; increasing prevalence of chronic ailments such as cancer and cardiac disease; growing awareness among patients; and heavy investments in clinical innovation are just some of the factors that are impacting the performance of the global healthcare industry. Proactive measures such as healthcare cost containment, primary care delivery, innovation in medical procedures (3-D printing, blockchain, and robotic surgery to name a few), safe and effective drug delivery, and well-defined healthcare regulatory compliance models are targeted at placing the sector on a high growth trajectory across key regional markets.

Parent Indicators Healthcare Current expenditure on health, % of gross domestic product Current expenditure on health, per capita, US$ purchasing power parities (current prices, current PPPs) Annual growth rate of current expenditure on health, per capita, in real terms Out-of-pocket expenditure, % of current expenditure on health Out-of-pocket expenditure, per capita, US$ purchasing power parity (current prices, current PPPs) Physicians, Density per 1000 population (head counts) Nurses, Density per 1000 population (head counts) Total hospital beds, per 1000 population Curative (acute) care beds, per 1000 population Medical technology, Magnetic Resonance Imaging units, total, per million population Medical technology, Computed Tomography scanners, total, per million population

Research Methodology

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XploreMR utilizes a triangulation methodology that is primarily based on experimental techniques such as patient-level data, to obtain precise market estimations and insights on Molecule and Drug Classes, API Formulations and preferred modes of administration. Bottom-up approach is always used to obtain insightful data for the specific country/regions. The country specific data is again analysed to derive data at a global level. This methodology ensures high quality and accuracy of information.

Secondary research is used at the initial phase to identify the age specific disease epidemiology, diagnosis rate and treatment pattern, as per disease indications. Each piece of information is eventually analysed during the entire research project which builds a strong base for the primary research information.

Primary research participants include demand-side users such as key opinion leaders, physicians, surgeons, nursing managers, clinical specialists who provide valuable insights on trends and clinical application of the drugs, key treatment patterns, adoption rate, and compliance rate.

Quantitative and qualitative assessment of basic factors driving demand, economic factors/cycles and growth rates and strategies utilized by key players in the market is analysed in detail while forecasting, in order to project Year-on-Year growth rates. These Y-o-Y growth projections are checked and aligned as per industry/product lifecycle and further utilized to develop market numbers at a holistic level.

On the other hand, we also analyse various companies annual reports, investor presentations, SEC filings, 10k reports and press release operating in this market segment to fetch substantial information about the market size, trends, opportunity, drivers, restraints and to analyse key players and their market shares. Key companies are segmented at Tier level based on their revenues, product portfolio and presence.

Please note that these are the partial steps that are being followed while developing the market size. Besides this, forecasting will be done based on our internal proprietary model which also uses different macro-economic factors such as per capita healthcare expenditure, disposable income, industry based demand driving factors impacting the market and its forecast trends apart from disease related factors.

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Standard Report Structure Executive Summary Market Definition Macro-economic analysis Parent Market Analysis Market Overview Forecast Factors Segmental Analysis and Forecast Regional Analysis Competition Analysis

Target Audience Production Companies Suppliers Channel Partners Marketing Authorities Subject Matter Experts Research Institutions Financial Institutions Market Consultants Government Authorities

Market Taxonomy

The global canine stem cell therapy market has been segmented into:

Product Type: Allogeneic Stem Cells Autologous Stem cells

Application: Arthritis Dysplasia Tendonitis Lameness Others

End User: Veterinary Hospitals Veterinary Clinics Veterinary Research Institutes

Region: North America Latin America Europe Asia Pacific Japan Middle East & Africa

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About Us

XploreMR is one of the worlds leading resellers of high-quality market research reports. We feature in-depth reports from some of the worlds most reputed market research companies and international organizations. We serve across a broad spectrum from Fortune 500 to small and medium businesses. Our clients trust us for our unwavering focus onquality and affordability. We believe high price should not be a bottleneck for organizations looking to gain access to quality information.

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Canine Stem Cell Therapy Market Will Make a Huge Impact in Near Future - News Times

Cardiac Stem Cells Comments Off on Canine Stem Cell Therapy Market Will Make a Huge Impact in Near Future – News Times | March 4th, 2020

10 things to know about stem cell therapy

New Delhi, March 3 (IANSlife) The usage of stem cells to cure or treat a disease or repair the injured tissue is defined as stem cell therapy. The best example of the stem cell treatment is seen in patients suffering from restoring the vision of the damaged eyes, grafting of the skin in severe burnt conditions. Stem cell treatments for brain or neural diseases like Parkinson''s and Alzheimer''s disease, multiple sclerosis, preventing heart strokes, curing diabetes, kidney disorders, autism, and spinal cord injuries are progressively making their way. Vipul Jain, CEO of Advancells and also a Serial entrepreneur, explains in detail the treatment, its uses, cost and effectiveness.

Q: What are stem cells?

Undifferentiated cells that are able to differentiate and transform into any type of cells of the body when and where needed. They have an enormous potential to repair, heal and regenerate. Stem cells come from blood, bone marrow, umbilical cord blood and adipose tissue.

Types of stem cell therapy

Autologous stem cell therapy: Patient receives stem cells from his/her own body

Allogeneic stem cell therapy: Patient receives the stem cells donated by another individual

Autologous stem cell therapy is better than allogeneic stem cell therapy as chances of mismatching are not there and they pose the minimum risk of immune rejection. Also, no side effects or adverse effects are seen as a person''s own blood cells are used. They start the healing process immediately in a natural way.

What is stem cell therapy?

The usage of stem cells to cure or treat a disease or repair the injured tissue is defined as stem cell therapy. Stem cells can be obtained from the bone marrow, adipose tissues etc. Due to their tremendous potential to prevent and to treat various health conditions and to repair the injured tissues global research investigation is continuously being done as to explore the maximum advantage of these cell lines.

The best example of the stem cell treatment is seen in patients suffering from restoring the vision of the damaged eyes, grafting of the skin in severe burnt conditions. Stem cell treatments for brain or neural diseases like Parkinson''s and Alzheimer''s disease, multiple sclerosis, preventing heart strokes, curing diabetes, kidney disorders, autism, and spinal cord injuries are progressively making their way.

What are the sources of stem cell?

Depending upon the disease, different stem cell source can be used in a specific condition. The procedure may involve the extraction of stem cells from adipose tissue-derived stem cells with the combination of PRP (Platelet-rich plasma) or can be obtained from bone marrow that can differentiate into progenitor cells that differentiate into various other tissues which can help in the therapy.

Procedure of stem cell therapy

The stem cells are isolated from the bone marrow or adipose tissues followed by their processing and enrichment under sterile conditions. These activated stem cells are placed back into the patient''s body at the target site for repairing the damaged tissue. It is necessary that the stem cells are injected in the specific area of injury as only then the desired results will be achieved.

Adipose stem cells are preferred over bone marrow stem cells as they are easy to isolate and contain a higher number of stem cells.

Stem cells injection

The stem cells injections are gaining much interest because it is devoid of the painful procedure, takes less time in comparison to a surgery, there are no host and recipient rejections as stem cells are harvested from the patient''s body itself and a targeted delivery system is available.

The stem cells obtained are processed in a sophisticated stem cell lab and after activation are inserted back into the host with the help of intravenous, intramuscular, intra-arterial, intradermal and intrathecal injections as per the requirement of the treatment process.

What is the use of anesthetics and why? Usually, local anesthetics are used during a stem cell procedure to numb the area but sometimes general anesthesia is also given while extracting the stem cells from bone marrow. But it is necessary to find out what anesthetic your doctor uses during orthopedic stem cell treatments.

A number of anesthetics have been found to kill the stem cells thus; the treatment''s end result will greatly depend on the use of anesthetics. Some anesthetics very well sync with the stem cell and hence, aid in the treatment.

How good are the processing techniques in the onsite labs?

Stem cells are to be extracted and processed in a clean room, under aseptic conditions maintaining a controlled environment. The doctor should explain the entire process and the number of viable stem cells infused into the patient during the process. Also, the precision of the injections to provide good quality of stem cells at the site of injury will help in better and faster recovery of the patient''s damaged area.

Duration and cost of the therapy

Cost of the treatment and its duration varies from one patient to another. The disease which needs to be cured, the severity, age factor, health condition, etc, define the duration of the therapy. One may respond during the treatment phase itself while the other may show results after a few sessions or weeks. Depending upon the disease diagnosed, the stem cells extracted, duration of the therapy, other adjuvants used in the process, the cost of the stem cell therapy can vary.

Follow-up visits

It is essential that after the stem cell therapy the patient should visit the stem cell doctor for recuperation therapies. The primary goals of such therapy is the prevention of secondary complications, analysis of recovery of motor, sensory and all the bodily functioning, psychological support/counseling for depression, mood swings or anxiety etc. and reintegration into the community.

There can be different sets of precautions which need to be followed at various steps for the recovery of the damaged tissues. The treatment and post treatment conditions may vary from person to person depending upon the disease and the severity.

Success rate of stem cell therapy

Stem cell therapy has shown results in treating serious ailments like leukemia, grafting tissues, autism, orthopedic conditions and skin problems etc. Stem Cell Therapy has been successfully used in the treatment of around 80 serious disorders.

Survival rates among patients who received stem cell treatment are significantly high, whether the cell donors are related or unrelated to them. With the ongoing research around the world, scientists are exploring new possibilities in which a number of life threatening diseases can be prevented and cured hence, the stem cells have proved to be promising in the near future as many aspects are yet to be revealed.

--IANS

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Disclaimer :- This story has not been edited by Outlook staff and is auto-generated from news agency feeds. Source: IANS

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10 things to know about stem cell therapy - Outlook India

Spinal Cord Stem Cells Comments Off on 10 things to know about stem cell therapy – Outlook India | March 4th, 2020