By Lorena Anderson, UC Merced

Professor Joel Spencer and his lab have made a huge breakthrough in stem cell research.

Professor Joel Spencer was a rising star in college soccer and now he is an emerging scientist in the world of biomedical engineering, capturing for the first time an image of a hematopoietic stem cell (HSC) within the bone marrow of a living organism.

Everyone knew black holes existed, but it took until last year to directly capture an image of one due to the complexity of their environment, Spencer said. Its analogous with stem cells in the bone marrow. Until now, our understanding of HSCs has been limited by the inability to directly visualize them in their native environment until now.

This work brings an advancement that will open doors to understanding how these cells work which may lead to better therapeutics for hematologic disorders including cancer.

Understanding how HSCs interact within their local environments might help researchers understand how cancers use this same environment in the bone marrow to evade treatment.

Spencer studied biological sciences at UC Irvine where he was the captain of the mens Division 1 soccer team. He initially planned to pursue a career in professional soccer until faculty mentors opened doors for research and introduced Spencer to biophotonics the science that deals with the interactions of light with biological matter.

UC faculty were a big part of my research experience; they became mentors and friends, Spencer said. My first foray into research was as a lab tech, and that is where I met people who were doing biomedical imaging, and it just caught my wonder.

An image of a stem cell in its natural niche

Spencer left his native California to earn his Ph.D. in bioengineering at Tufts University in Boston and took a postdoctoral research position in the Wellman Center for Photomedicine at Massachusetts General Hospital and Harvard Medical School. In Boston, he learned about live-animal imaging and his wonder became a passion.

Now his emphasis is on biomedical optics: building new microscopes and new imaging techniques to visualize and study biological molecules, cells and tissue in their natural niches in living, fully intact small animals.

I work at the interface of engineering and biology. My lab is seeking to answer biological questions that were impossible until the advancements in technology we have seen in the past couple decades, he said. You need to be able to peer inside an organ inside a live animal and see whats happening as it happens.

Based on work conducted at UC Merced and in Boston, he and his collaborators including his grad student Negar Tehrani visualized stem cells inside the bone marrow of live, intact mice.

He and his collaborators have a new paper published in the journal Nature detailing the work they conducted to study HSCs in their native environment in the bone marrow.

We can see how the cells behave in their native niches and how they respond to injuries or stresses which seems to be connected to the constant process of bone remodeling, Tehrani said. Researchers have been trying to answer questions that have gone unanswered for lack of technology, and they have turned to engineering to solve those puzzles.

Its important for researchers to understand the mechanics of stem cells because of the cells potential to regenerate and repair damaged tissue.

Spencer, left, and students from his lab

Spencer returned to California three years ago, joining the Department of Bioengineering in the School of Engineering at UC Merced. Hes also an affiliate of the Health Sciences Research Institute and the NSF CREST Center for Cellular and Biomolecular Machines . This is his third paper in Nature, but the first stemming from work conducted in his current lab.

He didnt come to UC Merced just because he loves biology Spencer also joined the campus because of the students.

Now Im back in the UC system Im a homegrown UC student whos now faculty, Spencer said. As a student within the system I was able to participate in myriad opportunities, including mentorships that advanced my career. Now I try to encourage graduate and undergrad students to follow their dreams. I love being able to give them opportunities its something I really want to do for the next generation.

Read the original here:
Breakthrough in Stem Cell Research: First Image of Niche Environment | Newsroom - UC Merced University News

Santiago Riviello-Goya, MD1; Aldo A. Acosta-Medina, MD2; Sergio I. Inclan-Alarcon, MD3; Sofa Garcia-Miranda, MD2; and Christianne Bourlon, MD, MHSc2

1Department of Medicine, Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico City, Mexico; 2Department of Hematology, Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico City, Mexico; 3Cancer Center, Centro Mdico ABC, Mexico City, Mexico

A 43-year-old male with a history of B-cell acute lymphoblastic leukemia (ALL), who underwent allogeneic hematopoietic stem cell transplantation (HSCT) 5 months prior, presented to the emergency department with a 5-day history of progressive bilateral lower extremity weakness. On physical examination, there were no additional neurologic findings; sensory function and urethral and anal sphincter tone were preserved.

Initial clinical laboratory testing showed peripheral blood cell counts, a peripheral blood smear, and a comprehensive metabolic panel within normal limits. Neuroimaging by computed tomography (CT) and magnetic resonance showed no evidence of acute intracranial processes or lesions suggestive of leukemic relapse. A lumbar puncture for cerebrospinal fluid (CSF) analysis was performed and documented the presence of lymphoid-appearing blasts (Figure 1). Flow cytometry (FC) confirmed central nervous system (CNS) infiltration by B-lineage lymphoid blasts (CD34+, CD45+, CD22+, CD19+, and CD10+) (Figure 2). Bone marrow aspirate and biopsy, including FC evaluation, were negative for systemic relapse. Bone marrow chimerism was 98%.

With a diagnosis of isolated extramedullary leukemic relapse (iEMR), the patient was initiated on weekly intrathecal chemotherapy and was weaned off graft-versus-host disease (GVHD) prophylaxis, achieving CSF clearance after 4 weeks of therapy. Against Hematology service recommendations, the patient declined systemic therapy and received only whole brain radiation therapy (24 Gy in 12 fractions).

The patient experienced remission of neurologic symptoms; however, after 5 months, he developed bilateral testicular tenderness and enlargement. An ultrasound was performed and was suggestive of leukemic infiltration (Figure 3). Chemotherapy with methotrexate and L-asparaginase in addition to radiotherapy to the testes (24 Gy in 12 fractions) was given without complications.

One year after initial CNS iEMR, the patient developed overt bone marrow relapse (BMR), as evidenced by development of bone pain throughout the lumbosacral region, and the appearance of multiple blastic and lytic lesions throughout the appendicular and axial skeleton. A positron emission tomography-CT scan documented abdominal lymphadenopathy (Figure 4). With this rapidly progressive picture, the patient was transitioned to supportive care and died 2 months later.

Is the risk of iEMR following HSCT modified by the choice of conditioning regimen? If so, which of the following approaches would have been the best choice to prevent iEMR in this patient?

A. There is no role of conditioning therapy in preventing iEMRB. Reduced intensity of regimen to favor graft-versus-leukemia (GVL) effectC. Nonmieloablative regimens including fludarabineD. Mieloablative regimens including total body irradiation (TBI)

CORRECT ANSWER: D. Mieloablative regimens including total body irradiation (TBI).

Allogeneic HSCT is an effective treatment for ALL, which can achieve long-term remission and even a potential cure.1 Antineoplastic activity is dependent on both high-dose chemotherapy and graft alloreactivity, with the latter manifested in the GVL effect, and undesirably yet inherently, in GVHD.2 Despite recent advances in allogeneic HSCT strategies, disease relapse is common and remains the most important cause of death in this population. Relapse is reported in 30% to 40% of patients but can increase to 60% in patients who are in a second complete remission (CR) at time of HSCT.2,3

Risk factors for relapse in patients with ALL who have undergone HSCT include disease- and transplant-related features. Reported high-risk disease characteristics include: hyperleukocytosis at diagnosis (white blood cell count >30 x109/L for B-lineage ALL and >100 x109/L for T-lineage ALL); cytogenetics associated with poor outcomes, including chromosome 11 translocations and t(9;22); a short remission timespan; more than a first CR; and a failed or delayed remission after induction therapy.4 In the HSCT population, transplant-related factors should be considered, including alternative donors other than those who are matched related and matched unrelated, the type of conditioning regimen, and the development of GVHD.2

ALL relapse following HSCT most commonly involves the medullary compartment, with a cumulative incidence of 41% at 5 years. Conversely, extramedullary relapse (EMR) is uncommon, with a 5-year cumulative incidence of 11.0% and 5.8% for EMR and iEMR, respectively.5 Due to the rarity of EMR, its prognostic impact remains controversial and the ideal management strategies are a subject of active study.

EMR is associated with poor clinical outcomes; however, the subgroup of patients with iEMR (as presented in this patient case) is gaining attention due to its increasing frequency, its role heralding a systemic relapse, and its clinical behavior showing better survival outcomes compared with BMR and EMR.6-8

Isolated EMR is defined as the presence of clonal blasts in any tissue other than the medullary compartment; bone marrow evaluation must show less than 5% of clonal blasts and a full donor chimerism. Most commonly affected sites include the skin, soft tissues, lymph nodes, and immune sanctuaries including the CNS and testes.1,5,9 Because prevention rather than treatment of relapse is related to improved survival outcomes, it is important to define subgroups of patients who may benefit fromearly intervention with a personalized transplant strategy.

Higher rates of iEMR have been linked to patients of younger age. This is thought to be secondary to: (1) a higher incidence of ALL compared with acute myeloid leukemia (AML) in this age subgroup, the former of which is most associated with EMR; (2) the relative overrepresentation of myelomonocytic/monocytic phenotypes in AML presenting in young individuals; and (3) the higher likelihood of a history of EMR in children compared with adults.1,10

A history of extramedullary (EM) disease, which has consistently been found to impact the development of iEMR, is preexistent in up to half of patients. In 2 out of 3 cases of EMR, disease affects the site of original EM involvement, possibly due to low efficacy of both high-dose chemotherapy and the GVL effect.1,5 An exception to this is CNS involvement, despite being a risk factor for subsequent CNS iEMR, which is commonly reported de novo, reflecting the protective effect of regularly administered prophylaxis to patients at high risk of CNS infiltration.11

The effect of GVHD on risk of iEMR is highly nuanced. Despite its well-known role as a protective factor for BMR, the same effect does not appear to hold true for iEMR.12 Initial reports in this population showed no differences in relapse-free survival regardless of acute or chronic GVHD (cGVHD) or a positive association between extensive cGVHD and iEMR development.10,13 This has led to investigators to postulate that the underlying physiopathology differs among different types of relapse, with decreased expression of human leukocyte antigen (HLA) minor histocompatibility antigens and adhesion molecules and decreased penetration of both immune cells and high-dose chemotherapy to EM sites.14 These mechanisms lead to decreased effectivness of T-cell dependent cytotoxicity of donor lymphocytes as compared with the medullary compartment, with subsequent clone selection and escape, enabling the development of iEMR.6

With the increased use of alternative donors, this has been contested in the haploidentical setting, with a recent report showing significantly increased rates of iEMR in patients who do not develop cGVHD. It is suggested that the role of GVL, coupled with GVHD, in this HLA-mismatched setting could partially explain the added benefit of GVHD in this subgroup. This report also evidenced increased tumor chemosensitivity in patients with EMR compared with BMR, possibly explained by reduced concentrations of conditioning therapy at EM sites.9

Cytogenetics associated with poor outcomes and advanced disease at the time of HSCT were described as risk factors for iEMR in initial cohort studies.1,5,10,15,16 However, recent publications that include alternative-donor HSCT recipients have reported that a haploidentical source could overcome this negative impact.9

The influence of type of conditioning regimen on likelihood of iEMR has been studied only retrospectively, mainly comparing TBI-based versus chemotherapy-based approaches. The landmark paper by Simpson et al showed a significantly elevated rate of iEMR in patients receiving busulfan-based conditioning. This finding has been related to the lack of penetration of drugs into the immune sanctuaries with chemotherapy-only regimens.17

Multiple approaches, including combination and single treatment for iEMR, have been described. Combination therapy including systemic chemotherapy plus local radiotherapy (or in CNS disease, radiation to the craniospinal axis, intrathecal chemotherapy, and systemic chemotherapy) has been associated with higher response rates than single-treatment strategies.9 Nonetheless, the best responses have been observed when combination therapy is followed by a cellular therapy (eg, second allogeneic HSCT, donor leukocyte infusion, and donor stem cell infusion), leading to CR rates of greater than 80%.5,13 Whether this increase in CR rate translates to an increase in survival outcomes remains debatable due to conflicting results in the current literature for iEMR.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

Corresponding author:

Christianne Bourlon, MD, MHScVasco de Quiroga No. 15.Belisario Domnguez Seccin XVI

Tlalpan, C.P. 14080, Ciudad de Mxico, Mxico

E-mail: chrisbourlon@hotmail.com

References:

1. Ge L, Ye F, Mao X, et al. Extramedullary relapse of acute leukemia after allogeneic hematopoietic stem cell transplantation: different characteristics between acute myelogenous leukemia and acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2014;20(7):1040-1047. doi: 10.1016/j.bbmt.2014.03.030.

2. Pavletic SZ, Kumar S, Mohty M, et al. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transplantation. Biol Blood Marrow Transplant. 2010;16(7):871-890. doi: 10.1016/j.bbmt.2010.04.004.

3. Devillier R, Crocchiolo R, Etienne A, et al. Outcome of relapse after allogeneic stem cell transplant in patients with acute myeloid leukemia. Leuk Lymphoma. 2013;54(6):1228-1234. doi: 10.3109/10428194.2012.741230.

4. Hoelzer D, Bassan R, Dombret H, Fielding A, Ribera JM, Buske C; ESMO Guidelines Committee. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v69-v82. doi: 10.1093/annonc/mdw025.

5. Shem-Tov N, Saraceni F, Danylesko I, et al. Isolated extramedullary relapse of acute leukemia after allogeneic stem cell transplantation: different kinetics and better prognosis than systemic relapse. Biol Blood Marrow Transplant. 2017;23(7):1087-1094. doi: 10.1016/j.bbmt.2017.03.023.

6. Lee JH, Choi SJ, Lee JH, et al. Anti-leukemic effect of graft-versus-host disease on bone marrow and extramedullary relapses in acute leukemia. Haematologica. 2005;90(10):1380-1388.

7. Xie N, Zhou J, Zhang Y, Yu F, Song Y. Extramedullary relapse of leukemia after allogeneic hematopoietic stem cell transplantation. Medicine (Baltimore). 2019;98(19):e15584. doi: 10.1097/MD.0000000000015584.

8. Shi JM, Meng XJ, Luo Y, et al. Clinical characteristics and outcome of isolated extramedullary relapse in acute leukemia after allogeneic stem cell transplantation: a single-center analysis. Leuk Res. 2013;37(4):372-377. doi: 10.1016/j.leukres.2012.12.002.

9. Mo XD, Kong J, Zhao T, et al. Extramedullary relapse of acute leukemia after haploidentical hematopoietic stem cell transplantation: incidence, risk factors, treatment, and clinical outcomes. Biol Blood Marrow Transplant. 2014;20(12):2023-2028. doi:10.1016/j.bbmt.2014.08.023.

10. Harris AC, Kitko CL, Couriel DR, et al. Extramedullary relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcomes. Haematologica. 2013;98(2):179-184. doi: 10.3324/haematol.2012.073189.

11. Hamdi A, Mawad R, Bassett R, et al. Central nervous system relapse in adults with acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(11):1767-1771. doi: 10.1016/j.bbmt.2014.07.005.

12. Giralt SA, Champlin RE. Leukemia relapse after allogeneic bone marrow transplantation: a review. Blood. 1994;84(11):3603-3612.

13. Solh M, DeFor TE, Weisdorf DJ, Kaufman DS. Extramedullary relapse of acute myelogenous leukemia after allogeneic hematopoietic stem cell transplantation: better prognosis than systemic relapse. Biol Blood Marrow Transplant. 2012;18(1):106-112. doi: 10.1016/j.bbmt.2011.05.023.

14. Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112(12):4371-4383. doi: 10.1182/blood-2008-03-077974.

15. Lee KH, Lee JH, Choi SJ, et al. Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course. Bone Marrow Transplant. 2003;32(8):835-842. doi: 10.1038/sj.bmt.1704223.

16. Clark WB, Strickland SA, Barrett AJ, Savani BN. Extramedullary relapses after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome. Haematologica. 2010;95(6):860-863.

17. Simpson DR, Nevill T, Shepherd JD, et al. High incidence of extramedullary relapse of AML after busulfan/cyclophosphamide conditioning and allogeneic stem cell transplantation. Bone Marrow Transplant. 1998;22(3):259-264. doi: 10.1038/sj.bmt.1701319.

Excerpt from:
Isolated Extramedullary Relapse in Acute Lymphoblastic Leukemia: What Can We Do Before and After Transplant? - Cancer Network

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.

To know Untapped Opportunities in the MarketCLICK HERE NOW

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.

Get Discount on Latest Report @CLICK HERE NOW

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.

Request TOC of the Reportfor more Industry Insights @CLICK HERE NOW

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 are Vericel 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.

Read the original here:
Regenerative Medicine Market Projected to Hit at a Strong CAGR Between Forecast Period 2017-2025 - Redhill Local Councillors

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.

To know Untapped Opportunities in the MarketCLICK HERE NOW

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.

Get Discount on Latest Report @CLICK HERE NOW

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.

Request TOC of the Reportfor more Industry Insights @CLICK HERE NOW

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 are Vericel 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.

Continued here:
Regenerative Medicine Market Analysis Trends, Growth Opportunities, Size, Type, Dynamic Demand and Drives with Forecast to 2025 - Jewish Life News

NEW YORK, Feb. 11, 2020 (GLOBE NEWSWIRE) -- BrainStorm Cell Therapeutics, Inc., (NASDAQ:BCLI), a leading developer of adult stem cell therapies for neurodegenerative diseases, today announced that the Company recently held a high level meeting with the U.S. Food and Drug Administration (FDA) to discuss potential NurOwn regulatory pathways for approval in ALS. Repeated intrathecal administration of NurOwn (autologous MSC-NTF cells) is currently being evaluated in a fully enrolled Phase 3 pivotal trial in ALS (NCT03280056).

In the planned meeting with senior Center for Biologics Evaluation and Research (CBER) leadership and several leading U.S. ALS experts, the FDA confirmed that the fully enrolled Phase 3 ALS trial is collecting relevant data critical to the assessment of NurOwn efficacy. The FDA indicated that they will look at the "totality of the evidence" in the expected Phase 3 clinical trial data. Furthermore, based on their detailed data assessment, they are committed to work collaboratively with BrainStorm to identify a regulatory pathway forward, including opportunities to expedite statistical review of data from the Phase 3 trial.

Both the FDA and BrainStorm acknowledged the urgent unmet need and the shared goal of moving much needed therapies for ALS forward as quickly as possible.

This is a key turning point in ourworktowardprovidingALSpatientswith a potential new therapy,said ChaimLebovits, President and CEO ofBrainStorm. We commend the FDA foritscommitmentto the ALS communityandtofacilitating the development, and we ultimately hope, the approvalofNurOwn.The entire BrainStorm team is grateful for the ongoing and conscientious collaboration in the quest to beat ALS.

Ralph Kern, MD, MHSc, Chief Operating Officer and Chief Medical Officer, stated, The entire team at BrainStorm has collectively worked to ensure that we conduct the finest, science-based clinical trials. We had the opportunity to communicate with Senior Leadership at the FDA and discuss how we can work together to navigate the approval process forward along a novel pathway. We appreciate their willingness and receptiveness to consider innovative approaches as we all seek to better serve the urgent unmet medical needs of the ALS community.

Brian Wallach, Co-Founder of I AM ALS stated: There is nothing more important to those living with ALS than having access to therapies that effectively combat this fatal disease. We have been working with BrainStorm for months now because we believe that NurOwn is a potentially transformative therapy in this fight. We were privileged to represent the patient voice at this meeting and are truly grateful to the company and the FDA for this critical agreement. This is a truly important moment of hope and we look forward to seeing both the Phase III data and the hopeful approval of NurOwn as soon as is possible.

About NurOwnNurOwn (autologous MSC-NTF cells) represent a promising investigational approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. NurOwn is currently being evaluated in a Phase 3 ALS randomized placebo-controlled trial and in a Phase 2 open-label multicenter trial in Progressive MS.

About BrainStorm Cell Therapeutics Inc.BrainStorm Cell Therapeutics Inc.is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwnCellular Therapeutic Technology Platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement as well as through its own patents, patent applications and proprietary know-how. Autologous MSC-NTF cells have received Orphan Drug status designation from theU.S. Food and Drug Administration(U.S.FDA) and theEuropean Medicines Agency(EMA) in ALS. BrainStorm has fully enrolled the Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six sites in the U.S., supported by a grant from theCalifornia Institute for Regenerative Medicine(CIRM CLIN2-0989). The pivotal study is intended to support a BLA filing for U.S.FDAapproval of autologous MSC-NTF cells in ALS. BrainStorm received U.S.FDAclearance to initiate a Phase 2 open-label multi-center trial of repeat intrathecal dosing of MSC-NTF cells in Progressive Multiple Sclerosis (NCT03799718) inDecember 2018and has been enrolling clinical trial participants sinceMarch 2019. For more information, visit the company'swebsite.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could causeBrainStorm Cell Therapeutics Inc.'sactual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorms need to raise additional capital, BrainStorms ability to continue as a going concern, regulatory approval of BrainStorms NurOwn treatment candidate, the success of BrainStorms product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorms NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorms ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorms ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

CONTACTS

Corporate:Uri YablonkaChief Business OfficerBrainStorm Cell Therapeutics Inc.Phone: 646-666-3188uri@brainstorm-cell.com

Media:Sean LeousWestwicke/ICR PRPhone: +1.646.677.1839sean.leous@icrinc.com

Or

Katie Gallagher | Account Director, PR and MarketingLaVoieHealthScience Strategic CommunicationsO: 617-374-8800 x109M: 617-792-3937kgallagher@lavoiehealthscience.com

View original post here:
BrainStorm Cell Therapeutics and FDA Agree to Potential NurOwn Regulatory Pathway for Approval in ALS - GlobeNewswire

NEW YORK, Feb. 10, 2020 (GLOBE NEWSWIRE) -- BrainStorm Cell Therapeutics, Inc. (NASDAQ:BCLI), a leading developer of adult stem cell therapies for neurodegenerative diseases, today announced that the Company will hold a conference call to update shareholders on financial results for the fourth quarter and full year ended December 31, 2019, and provide a corporate update, at 8:00 a.m., Eastern Time, on Tuesday, February 18, 2020.

BrainStorms President & CEO, Chaim Lebovits, will present the full year 2019 corporate update, after which, participant questions will be answered. Joining Mr. Lebovits to answer investment community questions will be Ralph Kern, MD, MHSc, Chief Operating Officer and Chief Medical Officer, and Preetam Shah, PhD, Chief Financial Officer.

Participants are encouraged to submit their questions prior to the call by sending them to: q@brainstorm-cell.com and questions should be submitted by 5:00 p.m., Eastern Time, Monday, February 17 2020.

The investment community may participate in the conference call by dialing the following numbers:

Those interested in listening to the conference call live via the internet may do so by visiting the Investors & Media page of BrainStorms website at http://www.ir.brainstorm-cell.com and clicking on the conference call link.

A webcast replay of the conference call will be available for 30 days on the Investors & Media page of BrainStorms website:

About NurOwn

NurOwn (autologous MSC-NTF cells) represent a promising investigational approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. NurOwn is currently being evaluated in a Phase 3 ALS randomized placebo-controlled trial and in a Phase 2 open-label multicenter trial in Progressive MS.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn Cellular Therapeutic Technology Platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement as well as through its own patents, patent applications and proprietary know-how. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA) in ALS. Brainstorm has fully enrolled the Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six sites in the U.S., supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a BLA filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. Brainstorm received U.S. FDA clearance to initiate a Phase 2 open-label multi-center trial of repeat intrathecal dosing of MSC-NTF cells in Progressive Multiple Sclerosis (NCT03799718) in December 2018 and has been enrolling clinical trial participants since March 2019. For more information, visit the company's website.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorms need to raise additional capital, BrainStorms ability to continue as a going concern, regulatory approval of BrainStorms NurOwn treatment candidate, the success of BrainStorms product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorms NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorms ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorms ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

CONTACTS

Investor Relations:Preetam Shah, MBA, PhDChief Financial OfficerBrainStorm Cell Therapeutics Inc.Phone: 862-397-8160pshah@brainstorm-cell.com

Media:Sean LeousWestwicke/ICR PRPhone: +1.646.677.1839sean.leous@icrinc.com

Read more from the original source:
BrainStorm Cell Therapeutics to Announce Fourth Quarter and Full Year 2019 Financial Results and Provide a Corporate Update - BioSpace

Testing a new therapeutic in human subjects for the first time is a major step in the translation of any novel treatment from the laboratory bench to clinical use.

When the therapeutic represents a paradigm shift, reaching this milestone is even more significant.

After years of planning, preparation and hard work to establish a base camp, starting human clinical trials is the first step towards the summit itself: gaining regulatory approval for product sales.

Exosomes tiny packets of proteins and nucleic acids (e.g. mRNA and miRNA) released by cells, that have powerful regenerative properties ranging from promoting wound healing to stimulating brain injury recovery following stroke represent just such a paradigm-shifting potential advance in human medicine.

The first commercial exosome therapeutics conference was held in Boston in September 2019 and over 15 companies participated.

This conference signals the emergence of exosomes as a new class of regenerative medicine products.

So far, just one or two of the companies working in the novel field of exosome-based therapies have reached the pivotal point and transitioned into human clinical trials. In this article we survey the field, starting with the pace-setters.

During the past few years, a handful of universities and research hospitals have carried out small scale, first-in-human Phase I clinical trials using exosomes. In each case where the study results are available, the exosome treatment was found to be safe and well-tolerated.

But the field has hotted up in the past few months, with the first companies reaching the pivotal point of testing exosome-based products in people.

On 28th January 2020, Melbourne-based Exopharm announced the first dosing under its first human clinical trial, becoming the first company to test exosomes potential for healing wounds in people.

The PLEXOVAL Phase I study will test Exopharms Plexaris product, a cell-free formulation of exosomes from platelets, which in preclinical animal studies have shown a regenerative effect, improving wound closure and reducing scarring.

The main readouts of the PLEXOVAL study the results of which are expected to be available sometime after mid-2020 will be safety, wound closure and scarring.

Joining Exopharm at the front of the pack is Maryland-based United Therapeutics.

Founded in 1996, United Therapeutics specialises in lung diseases and has a portfolio of FDA-approved conventional small molecule and biologic drugs on the market for a range of lung conditions.

On 26th June 2019, United Therapeutics announced approval for a Phase I trial (NCT03857841) of an exosome-based therapy against bronchopulmonary dysplasia (BDP), a condition common in preterm infants that receive assisted ventilation and supplemental oxygen.

Recruitment has commenced but dosing has not been announced. The study is due to conclude by December 2021. BDP is characterised by arrested lung growth and development, with health implications that can persist into adulthood.

Human clinical trials of a stem cell therapy for BDP, by Korean stem cell company Medipost, are already underway. However as with many stem cell therapies recent animal studies have shown that is the exosomes released by stem cells that are responsible for the therapeutic effect.

United Therapeutics therapy, UNEX-42, is a preparation of extracellular vesicles that are secreted from human bone marrow-derived mesenchymal stem cells. The company has not released any information about how its exosomes are produced or isolated.

A little behind the two leaders, three other companies have announced their aim to initiate their first clinical trials of exosome therapeutics within the next 12 months.

Launched in 2015, Cambridge, Massachusetts-based Codiak has long been considered among the leaders in developing exosome-based therapies.

Rather than exploiting the innate regenerative potential of select exosome populations, Codiak is developing engineered exosomes that feature a defined therapeutic payload. The companys initial focus has been to target immune cells, leveraging the immune system to combat cancer.

The company plans to initiate clinical trials of its lead candidate, exoSTING, in the first half of 2020. The therapeutic is designed to trigger a potent antitumor response from the patients own immune system, mediated by T cells. A second immuno-oncology candidate, exoIL-12, is due to enter clinical trials in the second half of 2020, the company says.

In nearby New Jersey, Avalon Globocare is also developing engineered exosomes. Its lead product, AVA-201, consists of exosomes enriched in the RNA miR-185, which are produced using engineered mesenchymal stem cells.

In animal tests, miR-185 suppressed cancer cell proliferation, invasion and migration in oral cancer. In July 2019, the company announced plans to start its first exosome clinical trial before the close of 2019. As of February 2020, however, no further announcement regarding this clinical trial has been made.

Avalon has also made no further announcement on a second planned clinical trial, also intended to start during the fourth quarter of 2019, of a second exosome candidate, AVA-202.

These angiogenic regenerative exosomes, derived from endothelial cells, can promote wound healing and blood vessel formation, the company says. The planned Phase I trial was to test AVA-202 for vascular diseases and wound healing.

Meanwhile, Miami-based Aegle Therapeutics plans to begin a Phase I/IIa clinical trial of its exosome therapy, AGLE-102, during 2020. AGLE-102 is based on native regenerative exosomes isolated from bone marrow mesenchymal stem cells.

After initially focussing on burns patients, in January 2020 to company announced had raised the funds to commence an FDA-cleared clinical trial of AGLE-102 to treat dystrophic epidermolysis bullosa, a rare paediatric skin blistering disorder. The company says it plans to commence this clinical trial in the first half of 2020.

A number of companies are in the preclinical phase of exosome therapy research.

Some of these companies have been set up specifically to develop exosome-based products. In the UK, Evox co-founded by University of Oxford researcher Matthew Wood in 2016 is developing engineered exosomes to treat rare diseases.

The company has developed or sourced technology that allows it to attach proteins to exosomes surface, or to load proteins or nucleic acids inside the exosome, to deliver a therapeutic cargo to a target organ.

Its lead candidate targets a lysosomal storage disorder called Niemann-Pick Disease type C, using exosomes that carry a protein therapeutic cargo. Evox says it plans to submit the Investigational New Drug (IND) application to the FDA during 2020, paving the way for the first clinical trial. It currently has five other candidates, for various indications, at the preclinical stage of development.

In Korea, Ilias and ExoCoBio are developing exosome therapeutics. Ilias founded by faculty from the Korean Advance Institute of Science and Technology specialises in loading large protein therapeutics into exosomes.

It is currently carrying out preclinical research toward treating sepsis, preterm labour and Gauchers disease. ExoCoBio is focusing on the native regenerative capacity of exosomes derived from mesenchymal stem cells, including to treat atopic dermatitis.

New companies continue to enter the exosome space. In August 2019, Carmine Therapeutics was launched, with the aim to develop gene therapies that utilize exosomes from red blood cells to deliver large nucleic acid cargoes. The company is targeting the areas of haematology, oncology and immunology.

Meanwhile, a wave of companies originally set up to develop live stem cell therapies are diversifying into stem cell derived exosome production and research.

It is now generally acknowledged that stem cell exosomes are the main therapeutically active component of stem cells, and that medical products based on exosomes will be safer to apply, and easier and cheaper to make and transport, than live cell therapies.

Originally established to produce neural stem cells for other research organisations, Aruna Bio has developed proprietary neural exosomes that can cross the blood brain barrier.

The company is now developing an exosome therapy for stroke. In October 2019, the Athens, Georgia-based company said had raised funding to support the research and development to enable its first IND application to the FDA in 2021.

In the UK, ReNeuron has also focussed on stroke, and has several clinical trials underway assessing its CTX stem cells to promote post stroke rehabilitation. The company is also working with third parties to investigate the drug- and gene therapy delivery potential of exosomes derived from CTX stem cells.

Switzerland-based Anjarium is also developing an exosome platform to selectively deliver therapeutics.20 The company is focussing on engineering exosomes loaded with therapeutic RNA cargo and displaying targeting moieties on its surface.

California-based Capricor has commenced clinical trials of a cardiosphere-derived stem cell therapy for the treatment of Duchenne muscular dystrophy (DMD).

At an earlier phase, its regenerative exosome therapy CAP-2003 is in pre-clinical development for a variety of inflammatory disorders including DMD.

A number of other stem cell companies, including TriArm, Creative Medical, AgeX Therapeutics and BrainStorm Cell Therapeutics, are reported to be investigating exosome-based therapies derived from their stem cell lines.

Exopharms position as a frontrunner in bringing exosomes into humans is no lucky accident. The companys operations are based around its unique, proprietary method for manufacturing and isolating exosomes, known as LEAP technology.

As academics and observers of the exosome field have pointed out, reliable and scalable exosome manufacture has threatened to be a major bottleneck that limits the translation of exosome therapeutics into clinical use. The standard laboratory-scale method for collecting the exosomes produced by cultured cells has been to spin the liquid cell culture medium in an ultracentrifuge, or pass it through a fine filter.

The most common technique used so far, the ultracentrifuge, has major scalability limitations. Issues include the high level of skill and manual labour required, the time-intensive nature of the process, and the associated costs of reagents and equipment. It is impossible to imagine collecting enough exosomes for a late stage clinical trial this way.

Another issue is the low purity of the exosomes collected. These techniques sort the contents of cell culture medium by their mass and/or size. Although the exosomes are concentrated, they could be accompanied by other biological components present in the cell culture medium that happen to be a similar size or mass to the exosome.

Importantly, a biotechnology company needs a proprietary step in the process to make a proprietary product over which it has exclusivity. Exopharms LEAP technology is a good example of a proprietary manufacturing step. Ultracentrifuge is not a proprietary process.

So the big players in the emerging exosome field have generally placed a strong emphasis on developing their manufacturing and purification capability.

Exopharm developed a chromatography-based purification method, in which a patent-applied-for inexpensive functionalised polymer a LEAP Ligand is loaded into a chromatography column. The LEAP Ligand sticks to the membrane surface of exosomes passed through the column. Everything else in the cell culture medium mixture is simply washed away. The pure exosome product is then eluted from the column and collected for use. As well as being very scalable, the technique is versatile. LEAP can be used to produce a range of exosome products, by isolating exosomes from different cell sources.

Codiak, similarly, says it has developed scalable, proprietary chromatography-based methods to produced exosomes with comparable identity, purity, and functional properties as exosomes purified using methods such as ultracentrifugation. Chromatography is a flow-based technique for separating mixtures. In an April 2019 SEC filing, the company said it is establishing its own Phase 1/2 clinical manufacturing facility, which it is aiming to have fully-operational by first half 2020.

Avalon GloboCare teamed up with Weill Cornell Medicine to develop a standardised production method for isolating clinical-grade exosomes. Aegle also says it has a proprietary isolation process for producing therapeutic-grade exosomes. And Evox emphasises the GMP compliant, scalable, commercially viable manufacturing platform it has developed.

At Exopharm, the manufacturing technique that has allowed the company to leap ahead of the pack and into human clinical trials is its proprietary LEAP platform. Overcoming the exosome production and isolation bottleneck was exactly the problem the companys scientists set out to solve when Exopharm formed in 2013.

In addition to the Plexaris exosomes, isolated from platelets, currently being tested in human clinical trials, Exopharm is progressing toward human clinical trials of its second product, Cevaris, which are exosomes isolated from stem cells.

Exosomes are now under development by around 20 companies across the world. The leaders in the field are now entering clinical trials with both nave exosome products and engineered exosome products. A number of cell therapy companies are also moving across into the promising exosome product space.

The coming years promise dynamic changes, with partnerships and eventually product commercialization. Exopharm is a clear leader in this emerging field.

(Featured image by Darko Stojanovic from Pixabay)

DISCLAIMER: This article was written by a third party contributor and does not reflect the opinion of Born2Invest, its management, staff or its associates. Please review our disclaimer for more information.

This article may include forward-looking statements. These forward-looking statements generally are identified by the words believe, project, estimate, become, plan, will, and similar expressions. These forward-looking statements involve known and unknown risks as well as uncertainties, including those discussed in the following cautionary statements and elsewhere in this article and on this site. Although the Company may believe that its expectations are based on reasonable assumptions, the actual results that the Company may achieve may differ materially from any forward-looking statements, which reflect the opinions of the management of the Company only as of the date hereof. Additionally, please make sure to read these important disclosures.

Link:
Biotech companies leading the way with exosome human clinical trials - Born2Invest

National Research (NASDAQ:NRC) and US Stem Cell (OTCMKTS:USRM) are both small-cap business services companies, but which is the better investment? We will compare the two businesses based on the strength of their earnings, dividends, valuation, profitability, institutional ownership, risk and analyst recommendations.

Analyst Recommendations

This is a breakdown of current ratings and target prices for National Research and US Stem Cell, as reported by MarketBeat.

Valuation & Earnings

This table compares National Research and US Stem Cells revenue, earnings per share (EPS) and valuation.

National Research has higher revenue and earnings than US Stem Cell.

Institutional & Insider Ownership

39.6% of National Research shares are owned by institutional investors. 4.5% of National Research shares are owned by company insiders. Comparatively, 16.7% of US Stem Cell shares are owned by company insiders. Strong institutional ownership is an indication that large money managers, hedge funds and endowments believe a company is poised for long-term growth.

Profitability

This table compares National Research and US Stem Cells net margins, return on equity and return on assets.

Risk & Volatility

National Research has a beta of 0.77, indicating that its stock price is 23% less volatile than the S&P 500. Comparatively, US Stem Cell has a beta of 5.08, indicating that its stock price is 408% more volatile than the S&P 500.

Summary

National Research beats US Stem Cell on 7 of the 9 factors compared between the two stocks.

National Research Company Profile

National Research Corporation (NRC) is a provider of analytics and insights that facilitate revenue growth, patient, employee and customer retention and patient engagement for healthcare providers, payers and other healthcare organizations. The Companys portfolio of subscription-based solutions provides information and analysis to healthcare organizations and payers across a range of mission-critical, constituent-related elements, including patient experience and satisfaction, community population health risks, workforce engagement, community perceptions, and physician engagement. The Companys clients range from acute care hospitals and post-acute providers, such as home health, long term care and hospice, to numerous payer organizations. The Company derives its revenue from its annually renewable services, which include performance measurement and improvement services, healthcare analytics and governance education services.

US Stem Cell Company Profile

U.S. Stem Cell, Inc., a biotechnology company, focuses on the discovery, development, and commercialization of autologous cellular therapies for the treatment of chronic and acute heart damage, and vascular and autoimmune diseases in the United States and internationally. Its lead product candidates include MyoCell, a clinical therapy designed to populate regions of scar tissue within a patient's heart with autologous muscle cells or cells from a patient's body for enhancing cardiac function in chronic heart failure patients; and AdipoCell, a patient-derived cell therapy for the treatment of acute myocardial infarction, chronic heart ischemia, and lower limb ischemia. The company's product development pipeline includes MyoCell SDF-1, an autologous muscle-derived cellular therapy for improving cardiac function in chronic heart failure patients. It is also developing MyoCath, a deflecting tip needle injection catheter that is used to inject cells into cardiac tissue in therapeutic procedures to treat chronic heart ischemia and congestive heart failure. In addition, the company provides physician and patient based regenerative medicine/cell therapy training, cell collection, and cell storage services; and cell collection and treatment kits for humans and animals, as well operates a cell therapy clinic. The company was formerly known as Bioheart, Inc. and changed its name to U.S. Stem Cell, Inc. in October 2015. U.S. Stem Cell, Inc. was founded in 1999 and is headquartered in Sunrise, Florida.

Receive News & Ratings for National Research Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for National Research and related companies with MarketBeat.com's FREE daily email newsletter.

Go here to read the rest:
Reviewing National Research (NASDAQ:NRC) and US Stem Cell (NASDAQ:USRM) - Slater Sentinel

National Research (NASDAQ:NRC) and US Stem Cell (OTCMKTS:USRM) are both small-cap business services companies, but which is the superior business? We will compare the two businesses based on the strength of their earnings, dividends, risk, institutional ownership, profitability, analyst recommendations and valuation.

Volatility & Risk

National Research has a beta of 0.77, indicating that its share price is 23% less volatile than the S&P 500. Comparatively, US Stem Cell has a beta of 5.08, indicating that its share price is 408% more volatile than the S&P 500.

Earnings and Valuation

This table compares National Research and US Stem Cells revenue, earnings per share and valuation.

National Research has higher revenue and earnings than US Stem Cell.

Analyst Ratings

This is a summary of recent recommendations and price targets for National Research and US Stem Cell, as reported by MarketBeat.com.

Insider and Institutional Ownership

39.6% of National Research shares are held by institutional investors. 4.5% of National Research shares are held by insiders. Comparatively, 16.7% of US Stem Cell shares are held by insiders. Strong institutional ownership is an indication that endowments, hedge funds and large money managers believe a stock is poised for long-term growth.

Profitability

This table compares National Research and US Stem Cells net margins, return on equity and return on assets.

Summary

National Research beats US Stem Cell on 7 of the 9 factors compared between the two stocks.

National Research Company Profile

National Research Corporation (NRC) is a provider of analytics and insights that facilitate revenue growth, patient, employee and customer retention and patient engagement for healthcare providers, payers and other healthcare organizations. The Companys portfolio of subscription-based solutions provides information and analysis to healthcare organizations and payers across a range of mission-critical, constituent-related elements, including patient experience and satisfaction, community population health risks, workforce engagement, community perceptions, and physician engagement. The Companys clients range from acute care hospitals and post-acute providers, such as home health, long term care and hospice, to numerous payer organizations. The Company derives its revenue from its annually renewable services, which include performance measurement and improvement services, healthcare analytics and governance education services.

US Stem Cell Company Profile

U.S. Stem Cell, Inc., a biotechnology company, focuses on the discovery, development, and commercialization of autologous cellular therapies for the treatment of chronic and acute heart damage, and vascular and autoimmune diseases in the United States and internationally. Its lead product candidates include MyoCell, a clinical therapy designed to populate regions of scar tissue within a patient's heart with autologous muscle cells or cells from a patient's body for enhancing cardiac function in chronic heart failure patients; and AdipoCell, a patient-derived cell therapy for the treatment of acute myocardial infarction, chronic heart ischemia, and lower limb ischemia. The company's product development pipeline includes MyoCell SDF-1, an autologous muscle-derived cellular therapy for improving cardiac function in chronic heart failure patients. It is also developing MyoCath, a deflecting tip needle injection catheter that is used to inject cells into cardiac tissue in therapeutic procedures to treat chronic heart ischemia and congestive heart failure. In addition, the company provides physician and patient based regenerative medicine/cell therapy training, cell collection, and cell storage services; and cell collection and treatment kits for humans and animals, as well operates a cell therapy clinic. The company was formerly known as Bioheart, Inc. and changed its name to U.S. Stem Cell, Inc. in October 2015. U.S. Stem Cell, Inc. was founded in 1999 and is headquartered in Sunrise, Florida.

Receive News & Ratings for National Research Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for National Research and related companies with MarketBeat.com's FREE daily email newsletter.

Follow this link:
Reviewing US Stem Cell (OTCMKTS:USRM) & National Research (OTCMKTS:NRC) - Riverton Roll

Like most medical students, I struggled to memorize the Krebs cycle, the complex energy-producing process that takes place in the body's mitochondria. Rote learning of Sir Hans Krebs' eponymous cascade of reactions persists and has been cited as a waste of time in modern medical education. However, it looks like that specialized knowledge about mitochondrial structure and function may finally come in handy in the clinic.

Advances in genetics have contributed to improved diagnostic accuracy of a diverse spectrum of mitochondrial disorders. Respiratory chain, nuclear gene, and mitochondrial proteome mutations can lead to multisystem or organ-specific dysfunction.

A new potential treatment for mitochondrial disorders, elamipretide, has received orphan drug designation from the US Food and Drug Administration (FDA) and is in clinical trials sponsored by Stealth Biotherapeutics. [Dr Wilner has consulted for Stealth Biotherapeutics.] Recently I had the opportunity to interview Hilary Vernon, MD, PhD, associate professor of genetic medicine at Johns Hopkins University, Baltimore, Maryland, and an expert on mitochondrial disorders. Dr Vernon discussed her research on elamipretide as a treatment for Barth syndrome, a rare form of mitochondrial disease.

I am the director of the Mitochondrial Medicine Center at Johns Hopkins Hospital. I work with individuals from infancy through adulthood who have mitochondrial conditions. I became interested in this particular area when I was early in my pediatrics/genetics residency at Johns Hopkins and saw the toll that mitochondrial disorders took on patients' lives and the limited effective therapies. At that point, I decided to focus on patient care and research in this area.

Mitochondrial disorders can be difficult to recognize because of their inherent multisystem nature and variable presentations (even between affected members of the same family). However, there are several considerations that should raise a clinician's suspicion for a mitochondrial condition. Ascertaining a family history of disease inheritance through the maternal line can raise the suspicion for a mitochondrial DNA disorder. Identification of a combination of medical issues in different organ systems that are seemingly unrelated in an individual (ie, optic atrophy and muscle weakness or diabetes and hearing loss) can also raise suspicion for a mitochondrial condition.

Due to the nature of mitochondria as the major energy producers of the cells, high-energy-requiring tissues such as the brain and the muscles are often affected. Perhaps the best known mitochondrial diseases to neurologists are MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) as well as MERFF (myoclonic epilepsy with ragged red fibers). There is a nice body of literature on the effects of arginine and citrulline in modifying stroke-like episodes in MELAS, and this is a therapy that is in current practice.

Mitochondria are complex organelles whose structure and function are encoded in hundreds of genes originating from both the nucleus of the cell and the mitochondria themselves. Mitochondria have many key roles in cellular function, including energy production through the respiratory chain, coordination of apoptosis, nitrogen metabolism, fatty acid oxidation, and much more.

Various cofactors and vitamins can be employed to improve mitochondrial function for different reasons. For example, if a specific enzyme is dysfunctional, supplying the cofactor for that enzyme may improve its function (ie, pyruvate dehydrogenase and thiamine). Antioxidants have also been considered to help reduce the oxidant load that could potentially cause ongoing damage to the mitochondrial membrane resulting from respiratory chain dysfunction (ie, coenzyme Q-10).

It is important to remember that the highest number of individual mitochondrial disorders result from mutations in genes located in the nuclear DNA. For example, the TAZ gene that is abnormal in Barth syndrome is a nuclear gene located on the X chromosome. These genes are amenable to the "regular" approaches to gene therapy.

Targeting mitochondrial DNA for gene therapy requires a different set of approaches because the gene delivery has to overcome the barrier of the mitochondrial membranes. However, research is ongoing to overcome these obstacles.

Barth syndrome is a very rare genetic X-linked disorder that usually only affects males. The genetic defect leads to an abnormal composition of cardiolipin on the inner mitochondrial membrane. Cardiolipin is an important phospholipid involved in many mitochondrial functions, including organization of inner mitochondrial membrane cristae, involvement in apoptosis, and organization of the respiratory chain (which is responsible for producing ATP via the process of oxidative phosphorylation), and many of these functions are abnormal in Barth syndrome. Individuals with Barth syndrome typically have early-onset cardiomyopathy, myopathy, intermittent neutropenia, fatigue, poor early growth, among other health concerns.

Early in my post-residency career, I followed several patients with Barth syndrome and was quickly welcomed into the Barth syndrome community by the families and the Barth Syndrome Foundation. From there, I founded the only interdisciplinary Barth syndrome clinic in the US and began to focus a significant amount of my clinical and laboratory research on this condition.

Most commonly, these individuals come to medical attention because of cardiomyopathy, but a minority of patients do come to attention due to repeated infections and neutropenia. Patients were identified for study participation through the Barth Syndrome Foundation or because they were already patients of my study team.

All participants were known to have Barth syndrome prior to study entry, and all had confirmatory genetic testing showing a pathogenic mutation in the TAZ gene.

By binding to cardiolipin in the inner mitochondrial membrane, elamipretide is believed to stabilize cristae architecture and electron transport chain structure during oxidative stress. I thought it would be great if this could help to stabilize the abnormal cardiolipin components on the inner mitochondrial membrane in Barth syndrome.

We observed improvements in several areas across the study population in the open-label extension part of the study. This includes a significant improvement in exercise performance (as measured by the 6-minute walk test, with an average improvement of 95.9 meters at 36 weeks) and a significant improvement in muscle strength. We also observed a potential improvement in cardiac stroke volume. Most of the adverse events were local injection-site reactions and were mild to moderate in nature.

The TAZPOWER trial has an ongoing open-label extension with the same endpoints as the placebo-controlled portion evaluated on an ongoing basis. In addition, in my laboratory, we are using induced pluripotent stem cells to learn more about how cardiolipin abnormalities affect different cell types in an effort to understand the tissue specificity of disease. This will help us to understand whether different aspects of Barth syndrome would necessitate individual management or clinical monitoring strategies.

Mitochondrial inner membrane dysfunction is increasingly recognized as a major aspect of the pathology of a wide range of mitochondrial conditions. Therefore, based on the role of stabilizing mitochondrial membrane components, elamipretide has a potential role in many disorders of the mitochondria.

Yes, this is what we would call "secondary mitochondrial dysfunction" (meant to differentiate from "primary mitochondrial disease," which is caused by defects in genes that encode for mitochondrial structure and function). Approaches intended to protect the mitochondria from further damage, such as antioxidants or strategies that can bypass the mitochondria for ATP production, could overlap as treatment for primary mitochondrial disease and secondary mitochondrial dysfunction.

This is something that is much discussed as a newer consideration for families who are affected by disorders of the mitochondrial DNA, but not something I have experience with firsthand.

Yes. The United Mitochondrial Disease Foundation and the Mitochondrial Medicine Society collaborated to develop the Mito Care Network, with 19 sites identified as Mitochondrial Medicine Centers across the US.

Andrew Wilner is an associate professor of neurology at the University of Tennessee Health Science Center in Memphis, a health journalist, and an avid SCUBA diver. His latest book is The Locum Life: A Physician's Guide to Locum Tenens.

Follow Dr Wilner on Twitter

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

Read the original:
Maybe Memorizing the Krebs Cycle Was Worthwhile After All - Medscape

Hip replacements, severe burns, spinal cord injuries, blast injuries, traumatic brain injuriesthese seemingly disparate traumas can each lead to a painful complication during the healing process called heterotopic ossification. Heterotopic ossification is abnormal bone formation within muscle and soft tissues, an unfortunately common phenomenon that typically occurs weeks after an injury or surgery. Patients with heterotopic ossification experience decreased range of motion, swelling and pain.

Currently, theres no way to prevent it and once its formed, theres no way to reverse it, says Benjamin Levi, M.D., Director of the Burn/Wound/Regeneration Medicine Laboratory and Center for Basic and Translational Research in Michigan Medicines Department of Surgery. And while experts suspected that heterotopic ossification was somehow linked to inflammation, new U-M research explains how this happens on a cellular scaleand suggests a way it can be stopped.

To help explain how the healing process goes awry in heterotopic ossification, the research team, led by Levi, Michael Sorkin, M.D. and Amanda Huber, Ph.D., of the Department of Surgerys section of plastic surgery, took a closer look at the inflammation process in mice. Using tissue from injury sites in mouse models of heterotopic ossification, they used single cell RNA sequencing to characterize the types of cells present. They confirmed that macrophages were among the first responders and might be behind aberrant healing.

Macrophages are white blood cells whose normal job is to find and destroy pathogens. Upon closer examination, the Michigan team found that macrophages are more complex than previously thoughtand dont always do what they are supposed to do.

Macrophages are a heterogenous population, some that are helpful with healing and some that are not, explains Levi. People think of macrophages as binary (M1 vs. M2). Yet weve shown that there are many different macrophage phenotypes or states that are present during abnormal wound healing.

Specifically, during heterotopic ossification formation, the increased presence of macrophages that express TGF-beta leads to an errant signal being sent to bone forming stem cells.

For now, the only way to treat heterotopic ossification is to wait for it to stop growing and cut it out which never completely restores joint function. This new research suggests that there may be a way to treat it at the cellular level. Working with the lab led by Stephen Kunkel, Ph.D. of the Department of Pathology, the team demonstrated that an activating peptide to CD47, p7N3 could alter TGF-beta expressing macrophages, reducing their ability to send signals to bone-forming stem cells that lead to heterotopic ossification.

During abnormal wound healing, we think there is some signal that continues to be present at an injury site even after the injury should have resolved, says Levi. Beyond heterotopic ossification, Levi says the studys findings can likely be translated to other types of abnormal wound healing like muscle fibrosis.

The team hopes to eventually develop translational therapies that target this pathway and further characterize not just the inflammatory cells but the stem cells responsible for the abnormal bone formation.

The paper is published in the journal Nature Communications. Other U-M authors include: Charles Hwang, William Carson IV, Rajarsee Menon, John Li, Kaetlin Vasquez, Chase Pagani, Nicole Patel, Shuli Li, Noelle D. Visser, Yashar Niknafs, Shawn Loder, Melissa Scola, Dylan Nycz, Katherine Gallagher, Laurie K. McCauley, Shailesh Agarwal, and Yuji Mishina.

Paper Cited: Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing, Nature Communications, DOI: 10.1038/s41467-019-14172-4

Read more from the original source:
Abnormal Bone Formation After Trauma Explained and Reversed in Mice - Michigan Medicine

Research into alternative stem cell sources has identified urine derived renal progenitor cells (UdRPCs) as a possible option for use in regenerative kidney therapies in the future.

Scientists have demonstrated their protocol for the reproducible isolation of kidney stem cells from human urine. These urine derived renal progenitor cells (UdRPCs) could be used to provide easier access to stem cells for regenerative kidney therapies and modelling diseases for R&D.

A shortage of donor organs and the risks and pain associated with bone marrow stem cell extractions and third trimester amniotic fluid collection have encouraged researchers to find alternative sources of stem cells. According to scientists, several laboratories have indicated urine could be an alternative source, at least for kidney stem cells, so the researchers from Heinrich Heine University-Duesseldorf (HHU) Germany,set out to complete a comprehensive molecular and cellular analysis of these cells.

UdRPCs should be considered as the choice of renal stem cells for facilitating the study of nephrogenesis, nephrotoxicity, disease modelling and drug development

Their study, published in Scientific Reports, revealed that UdRPCs isolated from ten individuals express both markers typically seen in bone marrow-derived mesenchymal stem cells (MSCs) and renal stem cells. The renal stem cell markers, according to the paper, allow UdRPCs to be differentiated into cell types present in the kidney, eg, podocytes and the proximal and distal tubules. The study also showed that these progenitor cells have similar properties to amniotic fluid-derived stem cells (AFCs).

Wasco Wruck, bioinformatician and co-author of the study, said: It is amazing that these valuable cells can be isolated from urine and comparing all the genes expressed in UdRPCs with that derived from kidney biopies we could confirm their renal and renal progenitor cell properties and origin.

According to Martina Bohndorf, a study co-author, UdRPCs can also be easily and efficiently reprogrammed into induced pluripotent stem cells using a non-viral integration-free and safe method.

Dr James Adjaye, study senior author and professor at the Institute for Stem Cell Research and Regenerative Medicine (ISRM) in the medical faculty of HHU, revealed that one of the most promising options in the near future is the use of transplantable renal stem cells (UdRPCs) for treatment of kidney diseases as a complementary option to kidney organs. He concluded that human UdRPCs should be considered as the choice of renal stem cells for facilitating the study of nephrogenesis, nephrotoxicity, disease modelling and drug development.

Read this article:
Kidney stem cells isolated from urine could be regenerative therapies - Drug Target Review

Mesoblast Tenders Completed Biologics License Application

Mesoblast Limited (MESO) announced that it has filed a completed Biologics License Application (BLA) with the United States Food and Drug Administration for its lead allogeneic cell therapy Ryoncil. The therapy is aimed at treating children with steroid-refractory acute graft versus host disease (SR-aGVHD).

Mesoblast submitted the final module of its rolling BLA submission on January 31, 2020. This module covers various aspects related to manufacturing and quality control. The drug candidate currently has Fast Track designation assigned to it and on the basis of this tag, the company is now seeking the FDA to carry out Priority Review of its BLA.

Subject to the approval of the therapy, the company is looking to launch it in the US markets in 2020. CEO Dr. Silviu Itescu said, "This is a major corporate milestone for Mesoblast." The company is expected to use the insights gained from its Temcell product in Japan for the marketing of Ryoncil.

Acute Graft versus Host disease affects nearly 50 percent of patients given an allogeneic Bone Marrow transplant. It is estimated that nearly 30,000 patients undergo bone marrow transplants worldwide. The mortality rate for patients suffering from actual GVHD is close to 90 percent. Currently, there is no FDA approved treatment for this in the United States for children under 12.

Ryoncil has been tested on 309 children suffering from SR-aGVHD during three different studies. It was employed as salvage therapy on 241 children with SR-aGVHD (80% Grade C/D) who failed institutional standard of care. It has also been tested as first line therapy for an open label Phase 3 trial in 55 children with SR-aGVHD. RYONCIL, is an investigational therapy comprising culture-expanded mesenchymal stem cells. These stem cells are taken from the bone marrow of an unrelated donor. The drug is administered to patients as intravenous infusions.

Mesoblast specializes in developing allogeneic cellular medicines. The company uses its proprietary cell therapy technology platform for research and development purpose. It has strong drug pipeline with products such as Remestemcel-L, Revascor, MPC-06-ID and MPC-300-IV. Revascor and MPC-06-ID have completed patient enrollment for its Phase 3 trials. The former drug candidate is aimed at treating advanced chronic heart failure while the latter is targeted at treating chronic low back pain caused by degenerative disc disease. The companys Temcell and Alofisel drugs are already approved in Japan and Europe, respectively.

Mesoblast has posted strong operative results as well. The company had reported 46 percent growth in its revenue during the first quarter of 2020. Mesoblast ended the quarter with $34.5 million in cash while its pro forma cash in hand stood at $100 million. The company also reported its strategic partnership with Grunenthal, which entitles Mesoblast to receive up to $150 million in upfront and milestone payments. The collaboration will also result in commercialization milestone payments. Such milestone payments have the potential to cross $1 billion mark.

Mesoblast stock has performed strongly in the market. The stock has charted over 200 percent in the past 12 months. Currently, it is trading close to its 52-week high of $10.88 and has potential to maintain its positive trajectory as the company forges ahead with its research and development activities and marketing efforts.

Waters Corporation (WAT) reported its fourth-quarter earnings and provided guidance for 2020. The company registered $716 million in revenue for the fourth quarter, in line with the revenue of $715 million it had reported for the corresponding quarter of the previous year. Its GAAP diluted earnings per share stood at $3.12 per share, up from $2.46 on year-on-year basis.

For the full fiscal year 2019, the companys revenue stood at $2.4 billion, down 1 percent from $2.42 billion in revenue it had earned in fiscal year 2018. The EPS for the fiscal year stood at $8.69, up from $7.65 for the previous year. The non GAAP EPS also increased from $8.29 to $8.99 for fiscal year 2019.

The company reported that its sales in both the pharmaceuticals and industrial market declined by 1 percent. However, its sales into the government and academic market grew 8 percent. Chris OConnell, Chairman and Chief Executive Officer of Waters Corporation, said, We were encouraged by the increasing impact in the fourth quarter of our new products launched during 2019.

While its full-year and fourth-quarter numbers were strong, the company provided rather lackluster guidance for fiscal year 2020. Waters Corporation expects its full-year revenue to increase by 1 percent to 3 percent. Its non GAAP EPS will likely remain between $9.15 and $9.40, lower than consensus estimate of $1.75. For its first quarter, Waters Corporations non GAAP EPS for the first quarter is expected to be in the range of $1.55 and $1.65. The consensus estimate for non GAAP EPS guidance was at $1.75.

EyePoint Pharmaceuticals (EYPT) reported its new exclusive licensing deal with Equinox Science. The deal involves the development of vorolanib for treating wet age-related macular degeneration, retinal vein occlusion and diabetic retinopathy. Vorolanib is a tyrosine kinase inhibitor.

EyePoint elaborated that its drug candidate EYP 1901, which incorporates vorolanib, uses a miniaturized, sustained release and injectable intravitreal drug delivery system offering six months duration. The company has used its bioerodible Durasert technology for this purpose. EyePoint is optimistic about the combination of vorolanib with Durasert technology for delivering superior results.

Under the terms of the agreement, EyePoint will take care of development and global commercialization of the treatment. However, the global commercialization will exclude China, Hong Kong, Taiwan and Macau regions. For this purpose, EyePoint will pay $1 million to Equinox Science as upfront payment. It will also pay development and regulatory milestones and post commercialization royalties.

EyePoint recently concluded a positive Type B pre investigational New Drug meeting with the FDA. The meeting clarified the pathway for a Phase 1 clinical trial. The company expects to present the data from Phase 1 trial during the second half of 2021. Nancy Lurker, President and Chief Executive Officer of EyePoint Pharmaceuticals, said, We are encouraged by the potential of vorolanib, as it demonstrated a promising Phase 1 and Phase 2 efficacy signal in prior human wAMD studies as an oral therapy and in preclinical animal studies as intravitreal EYP-1901.

EyePoint is a biopharma company specializing in developing novel ophthalmic products. The company currently has two products available in the market which are Dexycu and Yutiqu. The former is the first approved intraocular treatment for postoperative inflammation while the latter is a three-year treatment of chronic non-infectious uveitis affecting the posterior segment of the eye.

Thanks for reading. At the Total Pharma Tracker, we do more than follow biotech news. Using our IOMachine, our team of analysts work to be ahead of the curve.

That means that when the catalyst comes that will make or break a stock, weve positioned ourselves for success. And we share that positioning and all the analysis behind it with our members.

Disclosure: I am/we are long MESO. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Original post:
Mesoblast Submits BLA, And Other News: The Good, Bad And Ugly Of Biopharma - Seeking Alpha

'This is the beginning of my new life'

I thought my cancer diagnosis was a death sentence, said Lynnette Williams-Briggs, 60, of Seaford, Delaware, who was diagnosed with advanced B-cell lymphoma in 2018.

Briggs cancer is now in complete remission thanks to successful chimeric antigen receptor CAR-T cell therapy she received in August atChristianaCaresHelen F. Graham Cancer Center & Research InstitutesBone Marrow and Stem Cell Transplant Program.

I can breathe again. This is the beginning of my new life, Williams-Briggs said following the treatment that restored her hope for a second chance at life.

She was the first patient to receive CAR-T cell therapy in Delaware. A second patient was treated in December 2019, and doctors are preparing several more patients for CAR-T cell transplants in coming weeks.

The U.S. Food and Drug Administration has approved CAR-T cell therapy to treat patients like Williams-Briggs with highly resistant, B-cell blood cancers, for whom other available options have failed.

CAR-T cell therapy is only available at select cancer centers with specialized expertise in cellular therapies that are recognized for quality by the Foundation for the Accreditation of Cellular Therapy.

The Graham Cancer Centers Bone Marrow and Stem Cell Transplant Program is the only one in Delaware that is certified to treat adult patients with advanced B-cell lymphomas and children and young adults (to age 25) with acute lymphoblastic leukemia, using an FDA-approved drug.

CAR-T cell therapy is highly personalized medicine that attempts to use the bodys natural defenses to fight against cancer. The transplant team extracts millions of T cells, from the patients bloodstream, using a specialized blood filtration process called leukapheresis. The collected T cells are flash-frozen and sent to a lab for reprogramming, and then later infused back into the patient using a process similar to a blood transfusion.

The therapy is considered a living drug with potential benefits that could last for years.

When we first met Ms. Williams-Briggs, her cancer had progressed rapidly despite a third round of chemotherapy, so we knew we had to move quickly, said Graham Cancer Center Hematologist Peter Abdelmessieh, D.O. He worked closely with the bone marrow/stem cell transplant team and Graham Cancer Center leadership over the course of just eight months to develop the CAR-T cell therapy program.

It was truly a team effort to bring CAR-T cell therapy to our community so quickly, Dr. Abdelmessieh said.

CAR-T cell therapy has been extremely effective for many patients like Williams-Briggs, whose PET scan at 90 days confirmed her remission.

The supercharged T cells Williams-Briggs received were genetically modified in the lab to sprout new surface tools that improve their ability to recognize, latch onto and destroy other cells (including cancer cells) that express a specific antigen called CD19. These reprogrammed cells continue to multiply in the body after treatment, remaining on guard to seek and destroy any new cancers that might develop.

With continued success in increasing numbers of patients, it is conceivable that in the not too distant future, CAR-T cell therapy could become the new standard of care, replacing chemotherapy and stem cell transplants for many cancers, Dr. Abdelmessieh said.

The extended recovery period for CAR-T cell therapy is generally two to three months. After the infusion, patients may spend up to three weeks in the hospital to monitor treatment response and any side effects.

During the first 30 days after leaving the hospital, patients are required to remain close to the treatment center for regular follow-up care.

The ability to offer potentially life-saving CAR-T cell therapy is one more reason our patients need not travel further than the Graham Cancer Center for state-of-the-science cancer treatment, said Nicholas J. Petrelli, M.D., Bank of America medical director of the Helen F. Graham Cancer Center & Research Institute.

The Bone Marrow and Stem Cell Transplant Program is an outstanding example of how well our clinical teams work together to drive innovation in patient care.

Although patients normally do not experience the side effects associated with chemotherapy, such as nausea, vomiting or hair loss, CAR-T cell therapy is not without risks. A common side effect, which Williams-Briggs also experienced, is cytokine release syndrome. This is an inflammatory condition that causes flu-like symptoms that may be mild or severe.

The transplant team responded quickly to manage her symptoms while she received expert care on the Bone Marrow Transplant and Oncology unit at Christiana Hospital.

From the moment I first met with my transplant team, I felt like I was part of one big loving family that extended beyond my own loved ones, Williams-Briggs said.

Dr. Abdelmessieh and my ChristianaCare family gave me hope to keep fighting when I really didnt think I would make it. I would have driven anywhere to get life-saving treatment, but I am thankful that I did not have to. I found my miracle closer to home.

See original here:
First CAR-T cell cancer therapy patient in Delaware - Dover Post

Electron micrograph showing ridges and grooves on MAP hydrogel microbeads caused by developing stem cells.

Courtsey of Daniel Alge

Baby diapers, contact lenses and gelatin dessert. While seemingly unrelated, these items have one thing in common theyre made of highly absorbent substances called hydrogels that have versatile applications. Recently, a type of biodegradable hydrogel, dubbed microporous annealed particle (MAP) hydrogel, has gained much attention for its potential to deliver stem cells for body tissue repair. But it is currently unclear how these jelly-like materials affect the growth of their precious cellular cargo, thereby limiting its use in regenerative medicine.

In a new study published in the November issue of Acta Biomaterialia, researchers at Texas A&M University have shown that MAP hydrogels, programmed to biodegrade at an optimum pace, create a fertile environment for bone stem cells to thrive and proliferate vigorously. They found the space created by the withering of MAP hydrogels creates room for the stem cells to grow, spread and form intricate cellular networks.

Our research now shows that stem cells flourish on degrading MAP hydrogels; they also remodel their local environment to better suit their needs, said Daniel Alge, assistant professor in the Department of Biomedical Engineering. These results have important implications for developing MAP hydrogel-based delivery systems, particularly for regenerative medicine where we want to deliver cells that will replace damaged tissues with new and healthy ones.

MAP hydrogels are a newer breed of injectable hydrogels. These soft materials are interconnected chains of extremely small beads made of polyethylene glycol, a synthetic polymer. Although the microbeads cannot themselves cling to cells, they can be engineered to present cell-binding proteins that can then attach to receptor molecules on the stem cells surface.

Once fastened onto the microbeads, the stem cells use the space between the spheres to grow and transform into specialized cells, like bone or skin cells. And so, when there is an injury, MAP hydrogels can be used to deliver these new cells to help tissues regenerate.

However, the health and behavior of stem cells within the MAP hydrogel environment has never been fully studied.

MAP hydrogels have superior mechanical and biocompatible properties, so in principle, they are a great platform to grow and maintain stem cells, Alge said. But people in the field really dont have a good understanding of how stem cells behave in these materials.

To address this question, the researchers studied the growth, spread and function of bone stem cells in MAP hydrogels. Alge and his team used three samples of MAP hydrogels that differed only in the speed at which they degraded, that is, either slow, fast or not at all.

First, for the stem cells to attach onto the MAP hydrogels, the researchers decorated the MAP hydrogels with a type of cell-binding protein. They then tracked the stem cells as they grew using a high-resolution, fluorescent microscope. The researchers also repeated the same experiment using another cell-binding protein to investigate if cell-binding proteins also affected stem cell development within the hydrogels.

To their surprise, Alges team found that for both types of cell-binding proteins, the MAP hydrogels that degraded the fastest had the largest population of stem cells. Furthermore, the cells were changing the shape of the MAP hydrogel as they spread and claimed more territory.

In the intact MAP hydrogel, we could still see the spherical microbeads and the material was quite undamaged, Alge said. By contrast, the cells were making ridges and grooves in the degrading MAP hydrogels, dynamically remodeling their environment.

The researchers also found that as the stem cells grew, the quantity of bone proteins produced by the growing stem cells depended on which cell-binding protein was initially used in the MAP hydrogel.

Alge noted that the insight gained through their study will greatly inform further research and development in MAP hydrogels for stem-cell therapies.

Although MAP hydrogel degradability profoundly affects the growth of the stem cells, we found that the interplay between the cell-binding proteins and the degradation is also important, he said. As we, as a field, make strides toward developing new MAP hydrogels for tissue engineering, we must look at the effects of both degradability and cell-binding proteins to best utilize these materials for regenerative medicine.

Other contributors to the research include Shangjing Xin from the Department of Biomedical Engineering at Texas A&M and Carl A. Gregory from the Institute for Regenerative Medicine at the Texas A&M Health Science Center.

This research was supported by funds from theNational Institute of Arthritis and Musculoskeletal and Skin Diseasesof the National Institutes of Health.

See original here:
Researchers Explore Hydrogels That Are Promising Materials For Delivering Therapeutic Cells - Texas A&M University

Blocking the movement of cells from the bone marrow by inhibiting the CXCL12/CXCR4/CXCR7 signaling axis is a potential strategy for treating endometriosis, a recent study done in mice suggests.

The study, titled CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking, was published in theJournal of Cellular and Molecular Medicine.

Bone marrow-derived cells (BMDCs) play important roles in the normal functioning of the endometrium. For instance, stem cells from the bone marrow are involved in endometrial regeneration. But BMDCs also are involved in the formation of lesions in endometriosis.

The movement of BMDCs to uterine tissue whether for normal physiological reasons or as part of disease development is driven in large part by the signaling protein CXCL12. It acts through two protein receptors: CXCR4 and CXCR7. This CXCL12/CXCR4/CXCR7 signaling axis has been shown to be overactive in women with endometriosis.

Given the central role of the CXCL12/CXCR4/CXCR7 axis on BMDCs trafficking and in the pathogenesis [development] of endometriosis, we hypothesized that blocking CXCR4 or CXCR7 in endometriosis would inhibit the growth of endometriosis, the researchers said.

The scientists first used mouse models of endometriosis in which BMDCs were labeled with a fluorescent marker to confirm the presence of these cells in endometriotic lesions.

The BMDCs made up just over 10% of the total number of cells in lesions. Further, BMDCs that expressed CXCR4 represented about 4.4% of total lesion cells, while BMDCs expressing CXCR7 made up about 1.4%. CXCL12 also was highly expressed within the lesions.

The researchers then pharmacologically blocked each of the receptors, using Plerixafor (AMD3100) against CXCR4, and CCX771 against CXCR7. Plerixafor is used in stem cell transplants given to treat certain types of blood cancer. CCX771 is a small molecule without currently approved clinical uses.

Both treatments significantly reduced the percentage of BMDCs in lesions, suggesting that blocking this signaling axis did indeed stop the movement of these cells.

In addition, when either Plerixafor or CCX771 was given immediately after endometriosis establishment, the size of the endometriotic lesions was reduced by more than half compared with control mice. Blood vessel density also was significantly reduced, by about 40% for both receptors.

The treatments also reduced the expression of inflammatory signaling molecules known to be elevated in endometriosis, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha).

In a separate experiment to further test the treatments potential, Plerixafor and CCX771 were administered a few weeks after the endometriosis lesions developed. This more closely models the preexisting lesions found in humans at the time of endometriosis diagnosis, the researchers said.

The results were similar to those seen in the earlier model: there were significant decreases in lesion size by about 60% as well as in levels of inflammatory signaling molecules.

Notably, neither drug had any detectable effect on hormone cycling in the mice, demonstrating that the effects of these agents worked [through] a hormone independent pathway, the researchers said.

Based on the data, the researchers concluded that blocking the CXCL12/CXCR4/CXCR7 signaling axis may treat endometriosis. However, these results alone do not demonstrate that this effect is directly because of reduced BMDC recruitment. It would be equally plausible to postulate that the effect is due to blocking CXCL12/CXCR4/CXCR7 signaling in the endometrial cells themselves, not BMDCs, the investigators said.

To test this idea, the team established endometriosis models in mice that were engineered so that the cells in their uteruses could not make CXCL12. There were no detectable differences between these endometriosis lesions and lesions in mice that could make CXCL12 in their uteruses. Further, Plerixafor had no detectable effect on human endometrial cells taken from people with endometriosis and treated in a dish.

This suggests that the beneficial effect induced by blocking CXCL12/CXCR4/CXCR7 signaling is due to an effect on cells outside of the uterus. Due to their prevalence in lesions, this most likely means BMDCs, the researchers said.

Clinical use [of these therapies] will likely depend on side effect profile; the effects of prolonged use are not well characterized, the team said. They added that future studies evaluating such drugs safety profiles and off-target effects, particularly with long-term use, will be needed before these results can be translated into clinical application.

CXCR4 and CXCR7 antagonists are promising novel, nonhormonal therapies for endometriosis, the researchers concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

Total Posts: 146

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

Excerpt from:
Blocking Bone Marrow Cell Movement May Be Non-Hormonal Treatment... - Endometriosis News Today

Kenneth Pettine's stem cell product to treat OA was tested on retired Navy SEALs

FORT COLLINS, CO / ACCESSWIRE / February 3, 2020 / Kenneth Pettine is proud to announce that his revolutionary mesenchymal stem cell product to treat osteoarthritis was recently tested on 33 former Navy SEALs (one is a medal of honor recipient).

Kenneth Pettine is co-founder of Paisley Laboratories and a co-developer of a bone marrow-derived mesenchymal stem cell active growth factor and exosome product that is anticipated to revolutionize regenerative medicine.

In this study, Extracellular Vesicle Isolate Product (EVIP) was injected into 33 retired Navy SEALs to assist with knee, shoulder, elbow, ankle, and wrist osteoarthritis. At three-month follow-up, the injection appeared both safe and effective, with improvements ranging from 40% to as high as 98%. The average improvement is over 70%.

"This is extremely promising and we are motivated to continue our clinical studies to improve the quality of life for patients," says Kenneth Pettine.

Kenneth Pettine notes in his study that over 50 million Americans require daily treatment for disability and pain associated with OA. Every year, over one million total hip and knee replacements are performed in the U.S. with direct costs of over $30 billion and indirect costs of over $200 billion, with these numbers expected to double in the next three years.

In addition to this trial, Kenneth Pettine has three additional clinical studies planned to evaluate his stem cell products to treat erectile dysfunction, chronic obstructive pulmonary disease (COPD), and chronic lower back pain from painful discs.

For more information, visit https://www.kenneth-pettine.com/

About Kenneth Pettine

Dr. Kenneth Pettine is a serial entrepreneur and published clinical researcher with over 30 years of experience as an orthopedic surgeon. He holds a medical degree from the University of Colorado School of Medicine and completed his master's degree in orthopedic surgery and residency at the Mayo Clinic in Rochester, Minnesota.

In 1991, Dr. Pettine founded the Rocky Mountain Associates in Orthopedic Medicine. Kenneth Pettine is also the founder of Paisley Laboratories and the co-founder of the Society for Ambulatory Spine Surgery. In addition, he co-invented the Prestige cervical artificial disc and the Maverick Artificial Disc. Dr. Pettine is the principal investigator of 18 FDA studies involving non-fusion implants, biologics, and stem cells. He holds the only two issued U.S. patents for performing stem cell joint and spinal injections and currently has 21 additional patents pending for bone marrow derived mesenchymal stem cell applications. Kenneth Pettine is also a philanthropist and currently has a scholarship program underway to help students fund their education.

For more information, visit https://www.kenneth-pettine.com/ or https://www.kennethpettinescholarship.com/

Contact

info@kenneth-pettine.com

https://www.kenneth-pettine.com/

SOURCE: Kenneth Pettine

View source version on accesswire.com: https://www.accesswire.com/574987/Dr-Kenneth-Pettine-Announces-Verification-of-Clinical-Safety-Trial

Link:
Dr. Kenneth Pettine Announces Verification of Clinical Safety Trial - Yahoo Finance

Three-dimensional printers have now assembled candy, clothing, and even mouse ovaries. But in the next decade, specialized bioprinters could begin to build functioning human organs in space. It turns out, the minimal gravity conditions in space may provide a more ideal environment for building organs than gravity-heavy Earth.

If successful, space-printed organs could help to shorten transplant waitlists and even eliminate organ rejection. Though they still have a long way to go, researchers at the International Space Station (ISS) hope to eventually assemble organs from adult human cells, including stem cells.

The medical field has only recently embraced 3D printing in general, particularly in biomedical fields like regenerative medicine and prosthetics. So far, these printers have produced early versions of blood vessels, bones, and different types of living tissue by churning out repeated layers of bioinka substance comprised of living human cells and other tissue thats meant to mimic the natural environment that surrounds growing organs.

Recently, researchers are finding that Earth might not be the best environment for growing freestanding organs. Because gravity is constantly pushing down on these delicate structures as they grow, researchers must surround the tissues in scaffolding, which can often debilitate the delicate veins and blood vessels and prevent the soon-to-be organs from growing and functioning properly. Within microgravity, however, soft tissues hold their shape naturally, without the need for surrounding supportan observation thats driven researchers to space.

And one manufacturing lab based in Indiana thinks its tech could play a key role in space. The 3D BioFabrication Facility (BFF) is a specialized 3D printer that uses bioink to build layers several times thinner than human hair. It cost about $7 million to build and employs the smallest print tips in existence.

The brainchild of spaceflight equipment developer Techshot and 3D printer manufacturer nScrypt, the BFF headed to the ISS in July 2019 aboard the SpaceX CRS-18.

Currently, the project focuses on building increasingly thick artificial cardiac tissue and delivering it back to Earth. Once the printed cardiac tissue reaches a certain thickness, it gets harder for researchers to ensure that a printed structures layers effectively grow into one another. Ultimately, though, theyd like the organs to arrive here fully formed.

Printed organs would eventually require vasculature and nerve endings to work properly, though that technology doesnt yet exist.

The next stagetesting heart patches under microscopes and within animalscould span over the next four years. As for whole organs, Techshot claims it plans to begin production after 2025. For now, the project is still in its infancy.

If you were to look at what we printed, it looks very modest, says Techshot vice president of corporate advancement Rich Boling. Its just a cuboid-type shape, this rectangular box. Were just trying to get cells to grow one layer into the next.

Cooking organs like pancakes

Compare the manufacturing process to cooking pancakes, Boling says. The space crew first creates a custom bioink pancake mix with the cells sent from Earth, which they load with syringe-like tools into the BFF.

Researchers then insert a cassette into the BFF containing a bioreactora system that mimics the normal bodily functions essential for growing healthy tissue, like providing nutrients and flushing out waste.

Approximately 200 miles below in Greenville, Indiana, Techshot engineers connect with ISS astronauts on a NASA-enabled secure digital pathway. The linkup allows Techshot to remotely command BFF functions like pump pressure, internal temperature, lighting, and print speed.

Next, the actual printing process occurs within the bioreactor and can take anywhere from moments to hours, depending on the shapes complexity. In the final production step, the cell-culturing ADvanced Space Experiment Processor (ADSEP) cooks the theoretical pancake; essentially, the ADSEP toughens up the printed tissue for its journey back to earth. This step could take anywhere from 12 to 45 days for different tissue types. When completed and hardened, the structure heads home.

The researchers have gone through three testing processes so far, each one getting more exact. This March, theyll begin the third round of experiments.

The bioprinter space race

The BFF lab is the sole team developing this specific type of microgravity bioprinter, Boling says. Theyre not the only ones looking to print human organs in space, though.

A Russian project has also entered the bioprinting space race, however their technique highly differs. Unlike the BFFs bioink layering method, Russian biotechnology laboratory 3D Bioprinting Solutions uses magnetic nanoparticles to produce tissue. An electromagnet creates a magnetic field in which levitating tissue forms the desired structuretechnology that appears ripped from the pages of a sci-fi novel.

After their bioprinter fell victim to an October 2018 spacecraft crash, 3D Bioprinting Solutions rebounded; the team now collaborates with US and Israeli researchers at the ISS. Last month, their crew created the first space-bioprinted bone tissue. Similar to the US project, 3D Bioprinting Solutions aims to manufacture functioning human tissues and organs for transplantation and general repair.

Just because we have the technology to do it, should we do it?

If the 3D BioFabrication Facility prospers in printing working human organs, theyd be subject to thorough regulation here on Earth. The US approval process is stringent for any drug, Rich Boling says, posing a challenge for this unprecedented invention. Techshot predicts at least 10 years for space-printed organs to achieve legal approval, though its an inexact estimate.

Along with regulatory acceptance, human tissue printed in microgravity may encounter societal pushback.

Each country maintains varying laws related to medical transplants. Yet as bioengineering advances into the the final frontier, the international scientific research community may need to shape new guidelines for collaboration among the stars.

As the commercialization of low-Earth orbit continues to ramp up in the next few years, it is certainly true that were going to have to take a very close look at the regulations that apply to that, says International Space Station U.S. National Laboratory interim chief scientist Michael Roberts. And some of those regulations are going to stray into questions related to ethics: Just because we have the technology to do it, should we do it?

Niki Vermeulen, a University of Edinburgh science technology and innovation studies lecturer, has researched the social implications of 3D bioprinting experiments. Like any Earth-bound project, she urges scientists not to get peoples hopes up too early in the process; individuals seeking organ transplants could read about the BFF online and think it could soon be ready to meet their needs.

The most important thing now, I think, is expectation management, Vermeulen says. Because its really quite difficult to do this, and of course we really dont know if its going to work. If it did, it would be amazing.

Another main issue is cost. Like other cutting-edge biotechnology innovations, the organs could also pose a major affordability challenge, she says. Techshot claims that a single space-printed organ could actually cost less than one from a human donor, since some people must pay for a lifetime of anti-rejection meds and/or multiple transplants. Theres currently no telling how long the BFF process would actually take, however, compared to the conventional donor route.

Plus, theres potential health risks for recipients: Techshot chief scientist Eugene Boland says cell manipulation always presents a possibility of genetic mutation. Modified stem cells can potentially cause cancer in recipients, for example.

The team is now working to define and minimize any dangers, he says. The BFF experiment adheres to the FDAs specific regulations for human cells, tissues, and cellular and tissue-based products.

Researchers on the ground now hope to perfect human cell manipulation: Over 100 US clinical trials presently test cultured autologous human cells, and several hundred test cultured stem cells with multiple origins.

What comes next

After the next round of printing tests this March, Techshot will share the bioprinter with companies and research institutions looking to print materials like cartilage, bone, and liver tissue. Theyre currently preparing the bioprinter for these additional uses, Boling says, which could advance health care as a whole.

To speed things up for space crews, Techshot is now building a cell factory that produces multiple cell types in orbit. This technology could cut down the number of cell deliveries between Earth and space.

The ISS has taken in plenty of commercial ventures in recent years, Michael Roberts says, and its getting crowded up there. Space-based experiments ramped up between 40 and 50 years ago, though until recently they mostly prioritized satellite communications and remote observation technology. Since then, satellites have shrunk from bus-sized to smaller than a shoebox.

Roberts has witnessed the scientific areas of interest broaden over the past decade to include medicine. Organizations like the National Institutes of Health are now looking to space to improve treatments, and everything from large pharmaceutical companies to small-scale startups want in.

Theyve got something stuck on every surface up there, he says.

As the ISS runs out of space and exterior attachment points, Roberts predicts that commercial ventures will build new facilities built for specific activities like manufacturing and plant growth. He sees it as a good opportunity for further innovation, since the ISS was originally designed for far more general purposes.

Space, as a whole, may start to look quite different from the first exploration age.

Baby boomers may remember glimpsing at a grainy, black-and-white moon landing five decades ago. Within the same lifetime, they could potentially observe the introduction of space-printed organs.

Read more:
Space might be the perfect place to grow human organs - Popular Science

As amphibians go, axolotls are pretty cute. These salamanders sport a Mona Lisa half-smile and red, frilly gills that make them look dressed up for a party. You might not want them at your soiree, though: Theyre also cannibals. While rare now in the wild, axolotls used to hatch en masse, and it was a salamander-eat-salamander world. In such a harsh nursery, they evolved or maybe kept the ability to regrow severed limbs.

Their regenerative powers are just incredible, says Joshua Currie, a biologist at the Lunenfeld-Tanenbaum Research Institute in Toronto whos been studying salamander regeneration since 2011. If an axolotl loses a limb, the appendage will grow back, at just the right size and orientation. Within weeks, the seam between old and new disappears completely.

And its not just legs: Axolotls can regenerate ovary and lung tissue, even parts of the brain and spinal cord.

The salamanders exceptional comeback from injury has been known for more than a century, and scientists have unraveled some of its secrets. It seals the amputation site with a special type of skin called wound epithelium, then builds a bit of tissue called the blastema, from which sprouts the new body part. But until recently, the fine details of the cells and molecules needed to create a leg from scratch have remained elusive.

With the recentsequencingandassemblyof the axolotls giant genome, though, and thedevelopment of techniques to modify the creatures genes in the lab,regeneration researchers are now poised to discover those details. In so doing, theyll likely identify salamander tricks that could be useful in human medicine

Already, studies are illuminating the cells involved, and defining the chemical ingredients needed. Perhaps, several decades from now, people, too, might regrow organs or limbs. In the nearer future, the findings suggest possible treatments for ways to promote wound-healing and treat blindness.

The idea of human regeneration has evolved from an if to a when in recent decades, says David Gardiner, a developmental biologist at the University of California, Irvine. Everybody now is assuming that its just a matter of time, he says. But, of course, theres still much to do.

In a working limb, cells and tissues are like the instruments in an orchestra: Each contributes actions, like musical notes, to create a symphony. Amputation results in cacophony, but salamanders can rap the conductors baton and reset the remaining tissue back to order and all the way back to the symphonys first movement, when they first grew a limb in the embryo.

The basic steps are known: When a limb is removed, be it by hungry sibling or curious experimenter, within minutes the axolotls blood will clot. Within hours, skin cells divide and crawl to cover the wound with a wound epidermis.

Next, cells from nearby tissues migrate to the amputation site, forming a blob of living matter. This blob, the blastema, is where all the magic happens, said Jessica Whited, a regenerative biologist at Harvard University, in a presentation in California last year. It forms a structure much like the developing embryos limb bud, from which limbs grow.

This movie shows immune cells, labeled to glow green, moving within a regenerating axolotl fingertip. Scientists know that immune cells such as macrophages are essential for regeneration: When they are removed, the process is blocked.

Finally, cells in the blastema turn into all the tissues needed for the new limb and settle down in the right pattern, forming a tiny but perfect limb. This limb then grows to full size. When all is done, you cant even tell where the amputation occurred in the first place, Whited tellsKnowable Magazine.

Scientists know many of the molecular instruments, and some of the notes, involved in this regeneration symphony. But its taken a great deal of work.

As Currie started as a new postdoc with Elly Tanaka, a developmental biologist at the Research Institute of Molecular Pathology in Vienna, he recalls wondering, Where do the cells for regeneration come from? Consider cartilage. Does it arise from the same cells as it does in the developing embryo, called chondrocytes, that are left over in the limb stump? Or does it come from some other source?

To learn more, Currie figured out a way to watch individual cells under the microscope right as regeneration took place. First, he used a genetic trick to randomly tag the cells he was studying in a salamander with a rainbow of colors. Then, to keep things simple, he sliced off just a fingertip from his subjects. Next, he searched for cells that stuck out say, an orange cell that ended up surrounded by a sea of other cells colored green, yellow and so on. He tracked those standout cells, along with their color-matched descendants, over the weeks of limb regeneration. His observations, reported in the journalDevelopmental Cellin 2016,illuminated several secrets to the regeneration process.

Regenerative biologist Joshua Currie labeled the cells in axolotls with a rainbow of colors, so that he could follow their migration after he amputated the tip of the salamanders fingertips. In this image, three days after amputation, the skin (uncolored) has already covered the wound. (Credit: Josh Currie)

For one thing, cell travel is key. Cells are really extricating themselves from where they are and crawling to the amputation plane to form this blastema, Currie says. The distance cells will journey depends on the size of the injury. To make a new fingertip, the salamanders drew on cells within about 0.2 millimeters of the injury. But in other experiments where the salamanders had to replace a wrist and hand, cells came from as far as half a millimeter away.

More strikingly, Currie discovered that contributions to the blastema were not what hed initially expected, and varied from tissue to tissue. There were a lot of surprises, he says.

Chondrocytes, so important for making cartilage in embryos, didnt migrate to the blastema (earlier in 2016, Gardiner and colleaguesreported similar findings). And certain cells entering the blastema pericytes, cells that encircle blood vessels were able to make more of themselves, but nothing else.

The real virtuosos in regeneration were cells in skin called fibroblasts and periskeletal cells, which normally surround bone. They seemed to rewind their development so they could form all kinds of tissues in the new fingertip, morphing into new chondrocytes and other cell types, too.

To Curries surprise, these source cells didnt arrive all at once. Those first on the scene became chondrocytes. Latecomers turned into the soft connective tissues that surround the skeleton.

How do the cells do it? Currie, Tanaka and collaborators looked at connective tissues further, examining the genes turned on and off by individual cells in a regenerating limb. In a 2018Sciencepaper, the team reported thatcells reorganized their gene activation profileto one almost identical, Tanaka says, to those in the limb bud of a developing embryo.

Muscle, meanwhile, has its own variation on the regeneration theme. Mature muscle, in both salamanders and people, contains stem cells called satellite cells. These create new cells as muscles grow or require repair. In a 2017 study inPNAS, Tanaka and colleagues showed (by tracking satellite cells that were made to glow red) that most, if not all, ofmuscle in new limbs comes from satellite cells.

If Currie and Tanaka are investigating the instruments of the regeneration symphony, Catherine McCusker is decoding the melody they play, in the form of chemicals that push the process along. A regenerative biologist at the University of Massachusetts Boston, she recently published arecipe of sorts for creating an axolotl limb from a wound site. By replacing two of three key requirements with a chemical cocktail, McCusker and her colleagues could force salamanders to grow a new arm from a small wound on the side of a limb, giving them an extra arm.

Using what they know about regeneration, researchers at the University of Massachusetts tricked upper-arm tissue into growing an extra arm (green) atop the natural one (red). (Credit: Kaylee Wells/McCusker Lab)

The first requirement for limb regeneration is the presence of a wound, and formation of wound epithelium. But a second, scientists knew, was a nerve that can grow into the injured area. Either the nerve itself, or cells that it talks to, manufacture chemicals needed to make connective tissue become immature again and form a blastema. In their 2019 study inDevelopmental Biology, McCusker and colleagues guided byearlier work by a Japanese team used two growth factors, called BMP and FGF, to fulfill that step in salamanders lacking a nerve in the right place.

The third requirement was for fibroblasts from opposite sides of a wound to find and touch each other. In a hand amputation, for example, cells from the left and right sides of the wrist might meet to correctly pattern and orient the new hand. McCusckers chemical replacement for this requirement was retinoic acid, which the body makes from vitamin A. The chemical plays a role in setting up patterning in embryos and has long been known to pattern tissues during regeneration.

In their experiment, McCuskers team removed a small square of skin from the upper arm of 38 salamanders. Two days later, once the skin had healed over, the researchers made a tiny slit in the skin and slipped in a gelatin bead soaked in FGF and BMP. Thanks to that cocktail, in 25 animals the tissue created a blastema no nerve necessary.

About a week later, the group injected the animals with retinoic acid. In concert with other signals coming from the surrounding tissue, it acted as a pattern generator, and seven of the axolotls sprouted new arms out of the wound site.

The recipe is far from perfected: Some salamanders grew one new arm, some grew two, and some grew three, all out of the same wound spot. McCusker suspects that the gelatin bead got in the way of cells that control the limbs pattern. The key actions produced by the initial injury and wound epithelium also remain mysterious.

Its interesting that you can overcome some of these blocks with relatively few growth factors, comments Randal Voss, a biologist at the University of Kentucky in Lexington. We still dont completely know what happens in the very first moments.

If we did know those early steps, humans might be able to create the regeneration symphony. People already possess many of the cellular instruments, capable of playing the notes. We use essentially the same genes, in different ways, says Ken Poss, a regeneration biologist at the Duke University Medical Center in Durham who describednew advances in regeneration, thanks to genetic tools, in the 2017Annual Review of Genetics.

Regeneration may have been an ability we lost, rather than something salamanders gained. Way back in our evolutionary past, the common ancestors of people and salamanders could have been regenerators, since at least one distant relative of modern-day salamanders could do it. Paleontologists have discovered fossils of300-million-year-old amphibians with limb deformities typically created by imperfect regeneration.Other members of the animal kingdom, such as certain worms, fish and starfish, can also regenerate but its not clear if they use the same symphony score, Whited says.

These fossils suggest that amphibians calledMicromelerpetonwere regenerating limbs 300 million years ago. Thats because the fossils show deformities, such as fused bones, that usually occur when regrowth doesnt work quite right. (Credit: Nadia B Frbisch et al./Proceedings of the Royal Society B, 2014)

Somewhere in their genomes, all animals have the ability, says James Monaghan, a regeneration biologist at Northeastern University in Boston. After all, he points out, all animals grow body parts as embryos. And in fact, people arent entirely inept at regeneration. We can regrow fingertips, muscle, liver tissue and, to a certain extent, skin.

But for larger structures like limbs, our regeneration music falls apart. Human bodies take days to form skin over an injury, and without the crucial wound epithelium, our hopes for regeneration are dashed before it even starts. Instead, we scab and scar.

Its pretty far off in the future that we would be able to grow an entire limb, says McCusker. I hope Im wrong, but thats my feeling.

She thinks that other medical applications could come much sooner, though such as ways to help burn victims. When surgeons perform skin grafts, they frequently transfer the top layers of skin, or use lab-grown skin tissue. But its often an imperfect replacement for what was lost.

Thats because skin varies across the body; just compare the skin on your palm to that on your calf or armpit. The tissues that help skin to match its body position, giving it features like sweat glands and hair as appropriate, lie deeper than many grafts. The replacement skin, then, might not be just like the old skin. But if scientists could create skin with better positional information, they could make the transferred skin a better fit for its new location.

Monaghan, for his part, is thinking about regenerating retinas for people who have macular degeneration or eye trauma. Axolotls can regrow their retinas (though, surprisingly, their ability to regenerate the lens is limited to hatchlings). He is working with Northeastern University chemical engineer Rebecca Carrier, whos been developing materials for use in transplantations. Her collaborators are testing transplants in pigs and people, but find most of the transplanted cells are dying. Perhaps some additional material could create a pro-regeneration environment, and perhaps axolotls could suggest some ingredients.

Carrier and Monaghan experimented with the transplanted pig cells in lab dishes, and found they were more likely to survive and develop into retinal cells if grown together with axolotl retinas. The special ingredientseems to be a distinct set of chemicals that exist on axolotl, but not pig, retinas.Carrier hopes to use this information to create a chemical cocktail to help transplants succeed. Even partially restoring vision would be beneficial, Monaghan notes.

Thanks to genetic sequencing and modern molecular biology, researchers can continue to unlock the many remaining mysteries of regeneration: How does the wound epithelium create a regeneration-promoting environment? What determines which cells migrate into a blastema, and which stay put? How does the salamander manage to grow a new limb of exactly the right size, no larger, no smaller? These secrets and more remain hidden behind that Mona Lisa smile at least for now.

10.1146/knowable-012920-1

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews.

See the rest here:
What the Axolotl's Limb-Regenerating Capabilities Have to Teach Us - Discover Magazine

As amphibians go, axolotls are pretty cute. These salamanders sport a Mona Lisa half-smile and red, frilly gills that make them look dressed up for a party. You might not want them at your soiree, though: Theyre also cannibals. While rare now in the wild, axolotls used to hatch en masse, and it was a salamander-eat-salamander world. In such a harsh nursery, they evolved or maybe kept the ability to regrow severed limbs.

Their regenerative powers are just incredible, says Joshua Currie, a biologist at the Lunenfeld-Tanenbaum Research Institute in Toronto whos been studying salamander regeneration since 2011. If an axolotl loses a limb, the appendage will grow back, at just the right size and orientation. Within weeks, the seam between old and new disappears completely.

And its not just legs: Axolotls can regenerate ovary and lung tissue, even parts of the brain and spinal cord.

Unlike many amphibians, axolotls do not undergo metamorphosis. They stay in their aquatic, larval form (complete with frilly gills) even as they become sexually mature. They can regrow lost limbs, again and again, making them appealing to scientists who want to understand regeneration.

CREDIT: MARK LEAVER, PHD

The salamanders exceptional comeback from injury has been known for more than a century, and scientists have unraveled some of its secrets. It seals the amputation site with a special type of skin called wound epithelium, then builds a bit of tissue called the blastema, from which sprouts the new body part. But until recently, the fine details of the cells and molecules needed to create a leg from scratch have remained elusive.

With the recent sequencing and assembly of the axolotls giant genome, though, and the development of techniques to modify the creatures genes in the lab, regeneration researchers are now poised to discover those details. In so doing, theyll likely identify salamander tricks that could be useful in human medicine.

Already, studies are illuminating the cells involved, and defining the chemical ingredients needed. Perhaps, several decades from now, people, too, might regrow organs or limbs. In the nearer future, the findings suggest possible treatments for ways to promote wound-healing and treat blindness.

The idea of human regeneration has evolved from an if to a when in recent decades, says David Gardiner, a developmental biologist at the University of California, Irvine. Everybody now is assuming that its just a matter of time, he says. But, of course, theres still much to do.

In a working limb, cells and tissues are like the instruments in an orchestra: Each contributes actions, like musical notes, to create a symphony. Amputation results in cacophony, but salamanders can rap the conductors baton and reset the remaining tissue back to order and all the way back to the symphonys first movement, when they first grew a limb in the embryo.

The basic steps are known: When a limb is removed, be it by hungry sibling or curious experimenter, within minutes the axolotls blood will clot. Within hours, skin cells divide and crawl to cover the wound with a wound epidermis.

Next, cells from nearby tissues migrate to the amputation site, forming a blob of living matter. This blob, the blastema, is where all the magic happens, said Jessica Whited, a regenerative biologist at Harvard University, in a presentation in California last year. It forms a structure much like the developing embryos limb bud, from which limbs grow.

This movie shows immune cells, labeled to glow green, moving within a regenerating axolotl fingertip. Scientists know that immune cells such as macrophages are essential for regeneration: When they are removed, the process is blocked.

CREDIT: JOSH CURRIE

Finally, cells in the blastema turn into all the tissues needed for the new limb and settle down in the right pattern, forming a tiny but perfect limb. This limb then grows to full size. When all is done, you cant even tell where the amputation occurred in the first place, Whited tells Knowable Magazine.

Scientists know many of the molecular instruments, and some of the notes, involved in this regeneration symphony. But its taken a great deal of work.

As Currie started as a new postdoc with Elly Tanaka, a developmental biologist at the Research Institute of Molecular Pathology in Vienna, he recalls wondering, Where do the cells for regeneration come from? Consider cartilage. Does it arise from the same cells as it does in the developing embryo, called chondrocytes, that are left over in the limb stump? Or does it come from some other source?

To learn more, Currie figured out a way to watch individual cells under the microscope right as regeneration took place. First, he used a genetic trick to randomly tag the cells he was studying in a salamander with a rainbow of colors. Then, to keep things simple, he sliced off just a fingertip from his subjects. Next, he searched for cells that stuck out say, an orange cell that ended up surrounded by a sea of other cells colored green, yellow and so on. He tracked those standout cells, along with their color-matched descendants, over the weeks of limb regeneration. His observations, reported in the journal Developmental Cell in 2016, illuminated several secrets to the regeneration process.

Regenerative biologist Joshua Currie labeled the cells in axolotls with a rainbow of colors, so that he could follow their migration after he amputated the tip of the salamanders fingertips. In this image, three days after amputation, the skin (uncolored) has already covered the wound.

CREDIT: JOSH CURRIE

For one thing, cell travel is key. Cells are really extricating themselves from where they are and crawling to the amputation plane to form this blastema, Currie says. The distance cells will journey depends on the size of the injury. To make a new fingertip, the salamanders drew on cells within about 0.2 millimeters of the injury. But in other experiments where the salamanders had to replace a wrist and hand, cells came from as far as half a millimeter away.

More strikingly, Currie discovered that contributions to the blastema were not what hed initially expected, and varied from tissue to tissue. There were a lot of surprises, he says.

Chondrocytes, so important for making cartilage in embryos, didnt migrate to the blastema (earlier in 2016, Gardiner and colleagues reported similar findings). And certain cells entering the blastema pericytes, cells that encircle blood vessels were able to make more of themselves, but nothing else.

The real virtuosos in regeneration were cells in skin called fibroblasts and periskeletal cells, which normally surround bone. They seemed to rewind their development so they could form all kinds of tissues in the new fingertip, morphing into new chondrocytes and other cell types, too.

To Curries surprise, these source cells didnt arrive all at once. Those first on the scene became chondrocytes. Latecomers turned into the soft connective tissues that surround the skeleton.

How do the cells do it? Currie, Tanaka and collaborators looked at connective tissues further, examining the genes turned on and off by individual cells in a regenerating limb. In a 2018 Science paper, the team reported that cells reorganized their gene activation profile to one almost identical, Tanaka says, to those in the limb bud of a developing embryo.

Muscle, meanwhile, has its own variation on the regeneration theme. Mature muscle, in both salamanders and people, contains stem cells called satellite cells. These create new cells as muscles grow or require repair. In a 2017 study in PNAS, Tanaka and colleagues showed (by tracking satellite cells that were made to glow red) that most, if not all, of muscle in new limbs comes from satellite cells.

If Currie and Tanaka are investigating the instruments of the regeneration symphony, Catherine McCusker is decoding the melody they play, in the form of chemicals that push the process along. A regenerative biologist at the University of Massachusetts Boston, she recently published a recipe of sorts for creating an axolotl limb from a wound site. By replacing two of three key requirements with a chemical cocktail, McCusker and her colleagues could force salamanders to grow a new arm from a small wound on the side of a limb, giving them an extra arm.

Using what they know about regeneration, researchers at the University of Massachusetts tricked upper-arm tissue into growing an extra arm (green) atop the natural one (red).

CREDIT: KAYLEE WELLS / MCCUSKER LAB

The first requirement for limb regeneration is the presence of a wound, and formation of wound epithelium. But a second, scientists knew, was a nerve that can grow into the injured area. Either the nerve itself, or cells that it talks to, manufacture chemicals needed to make connective tissue become immature again and form a blastema. In their 2019 study in Developmental Biology, McCusker and colleagues guided by earlier work by a Japanese team used two growth factors, called BMP and FGF, to fulfill that step in salamanders lacking a nerve in the right place.

The third requirement was for fibroblasts from opposite sides of a wound to find and touch each other. In a hand amputation, for example, cells from the left and right sides of the wrist might meet to correctly pattern and orient the new hand. McCusckers chemical replacement for this requirement was retinoic acid, which the body makes from vitamin A. The chemical plays a role in setting up patterning in embryos and has long been known to pattern tissues during regeneration.

In their experiment, McCuskers team removed a small square of skin from the upper arm of 38 salamanders. Two days later, once the skin had healed over, the researchers made a tiny slit in the skin and slipped in a gelatin bead soaked in FGF and BMP. Thanks to that cocktail, in 25 animals the tissue created a blastema no nerve necessary.

About a week later, the group injected the animals with retinoic acid. In concert with other signals coming from the surrounding tissue, it acted as a pattern generator, and seven of the axolotls sprouted new arms out of the wound site.

The recipe is far from perfected: Some salamanders grew one new arm, some grew two, and some grew three, all out of the same wound spot. McCusker suspects that the gelatin bead got in the way of cells that control the limbs pattern. The key actions produced by the initial injury and wound epithelium also remain mysterious.

Its interesting that you can overcome some of these blocks with relatively few growth factors, comments Randal Voss, a biologist at the University of Kentucky in Lexington. We still dont completely know what happens in the very first moments.

If we did know those early steps, humans might be able to create the regeneration symphony. People already possess many of the cellular instruments, capable of playing the notes. We use essentially the same genes, in different ways, says Ken Poss, a regeneration biologist at the Duke University Medical Center in Durham who described new advances in regeneration, thanks to genetic tools, in the 2017 Annual Review of Genetics.

Regeneration may have been an ability we lost, rather than something salamanders gained. Way back in our evolutionary past, the common ancestors of people and salamanders could have been regenerators, since at least one distant relative of modern-day salamanders could do it. Paleontologists have discovered fossils of 300-million-year-old amphibians with limb deformities typically created by imperfect regeneration. Other members of the animal kingdom, such as certain worms, fish and starfish, can also regenerate but its not clear if they use the same symphony score, Whited says.

These fossils suggest that amphibians called Micromelerpeton were regenerating limbs 300 million years ago. Thats because the fossils show deformities, such as fused bones, that usually occur when regrowth doesnt work quite right.

CREDIT: NADIA B. FRBISCHET AL / PROCEEDINGS OF THE ROYAL SOCIETY B 2014

Somewhere in their genomes, all animals have the ability, says James Monaghan, a regeneration biologist at Northeastern University in Boston. After all, he points out, all animals grow body parts as embryos. And in fact, people arent entirely inept at regeneration. We can regrow fingertips, muscle, liver tissue and, to a certain extent, skin.

But for larger structures like limbs, our regeneration music falls apart. Human bodies take days to form skin over an injury, and without the crucial wound epithelium, our hopes for regeneration are dashed before it even starts. Instead, we scab and scar.

Its pretty far off in the future that we would be able to grow an entire limb, says McCusker. I hope Im wrong, but thats my feeling.

She thinks that other medical applications could come much sooner, though such as ways to help burn victims. When surgeons perform skin grafts, they frequently transfer the top layers of skin, or use lab-grown skin tissue. But its often an imperfect replacement for what was lost.

Thats because skin varies across the body; just compare the skin on your palm to that on your calf or armpit. The tissues that help skin to match its body position, giving it features like sweat glands and hair as appropriate, lie deeper than many grafts. The replacement skin, then, might not be just like the old skin. But if scientists could create skin with better positional information, they could make the transferred skin a better fit for its new location.

Monaghan, for his part, is thinking about regenerating retinas for people who have macular degeneration or eye trauma. Axolotls can regrow their retinas (though, surprisingly, their ability to regenerate the lens is limited to hatchlings). He is working with Northeastern University chemical engineer Rebecca Carrier, whos been developing materials for use in transplantations. Her collaborators are testing transplants in pigs and people, but find most of the transplanted cells are dying. Perhaps some additional material could create a pro-regeneration environment, and perhaps axolotls could suggest some ingredients.

Carrier and Monaghan experimented with the transplanted pig cells in lab dishes, and found they were more likely to survive and develop into retinal cells if grown together with axolotl retinas. The special ingredient seems to be a distinct set of chemicals that exist on axolotl, but not pig, retinas. Carrier hopes to use this information to create a chemical cocktail to help transplants succeed. Even partially restoring vision would be beneficial, Monaghan notes.

Thanks to genetic sequencing and modern molecular biology, researchers can continue to unlock the many remaining mysteries of regeneration: How does the wound epithelium create a regeneration-promoting environment? What determines which cells migrate into a blastema, and which stay put? How does the salamander manage to grow a new limb of exactly the right size, no larger, no smaller? These secrets and more remain hidden behind that Mona Lisa smile at least for now.

Continue reading here:
Regeneration: The amphibian's opus - Knowable Magazine