Mystified by the need for defibrillation to save a 10-year-old from drowning, Michael Ackerman, M.D., Ph.D., vowed to dig for answers. That pivotal case during a Mayo Clinic pediatric cardiology residency was the catalyst for Dr. Ackermans career in genetic sleuthing of inherited sudden cardiac death syndromes. With help from the Center for Regenerative Medicine Biotrust, Dr. Ackermans team reprograms cell lines to zero in on precise causes and possible treatments for genetic heart disorders that increase the risk of sudden cardiac death. His research and practice focus on inherited conditions like long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and Brugada syndrome (BrS) along with heart muscle diseases such as hypertrophic cardiomyopathy (HCM).

Working with the Center for Regenerative Medicine has opened up a whole new investigative arm to our lab. It is bench to bedside research. We take cells from a blood sample from my patients and then reprogram those cells to become cardiac cells. This research effort has been a powerful tool in gene discovery to prove beyond a shadow of a doubt when a monogenetic variant is indeed the cause of a sudden cardiac death syndrome, says Dr. Ackerman.

Reprogramming cells to identify disease-causing mutations

Reprogramming a patients cells is like a step back in time to when the cells were initially forming in the mothers womb. At that time, cells were dividing and could become any type of cell or tissue in the body. Reprogrammed cells, known as induced pluripotent stem cells, can be redirected to become new heart cells. Dr. Ackermans team uses these patient-specific cell lines to create a disease in a dish model and investigate whether genetic mutations are causing the patients genetic heart disease such as long QT syndrome.

Once we think weve found the root cause of disease, we then go to the patients cell line. We ask, does it show in the dish, in that patients re-engineered heart cells, a prolonged QT cellular phenotype? If it does, then we edit out and correct that variant of interest and at the cellular level test whether the abnormality disappears, says Dr. Ackerman.

Dr. Ackermans team then introduces that genetic variant into normal, healthy cells. If those cells produce a long QT phenotype, they have proof that exact genetic variant is the cause.

Using this disease in a dish model and other genetic sleuthing strategies, Dr. Ackermans team has discovered six of the 17 known genes that cause long QT syndrome. And, they have recently described two entirely new syndromes. One is triadin knockout syndrome, a heart arrhythmia that could lead to cardiac arrest in children during exercise. The second is an autosomal recessive genetic mechanism for calcium release channel deficiency syndrome, prevalent within Amish communities. That key discovery solved the mystery of why so many Amish children were dying suddenly during ordinary childhood play. The disease in a dish model is also useful for discovering new therapies. After creating the patients disease in a dish, Dr. Ackermans team tests potential new drug compounds to see if they could be effective.

We are developing a new gene therapy for the most common genetic subtype of long QT syndrome.With this model, the gene therapy vector is essentially curing the diseased long QT phenotype in the dish, says Dr. Ackerman.

Almost quit research

Dr. Ackerman began medical and graduate school at Mayo Clinic in 1988, where he worked in a research lab next to then fellow trainee, Andre Terzic, M.D., Ph.D., who now is director of Mayo Clinic Center for Regenerative Medicine. Initially not seeing the relevance to patient care, Dr. Ackerman finished his Ph.D. and left research vowing to never, ever return. True to his mentors predictions that youll be back, Mike, Dr. Ackerman felt the pull back to research to address unmet medical needs of his patients.He joined Mayo Clinics faculty in 2000 as one of the first genetic cardiologists with a goal of establishing a practice for patients at risk of sudden cardiac death from genetic heart diseases. Dr. Ackerman now directs the Mayo Clinic Windland Smith Rice Genetic Heart Rhythm Clinic and the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory.

Dr. Ackermans return to research has provided many answers for patients, with over 600 peer-reviewed publications that have occurred since that time 23 years ago when Dr. Ackerman and his team first solved that 10-year-old boys near fatal drowning. It was a mutation in the gene causing type 1 long QT syndrome.

Dr. Ackerman is one of the innovators the Center for Regenerative Medicine collaborates with as it seeks to be a global leader and trusted destination for regenerative care driven by research and education.

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Tags: Brugada syndrome, Center for Regenerative Medicine Biotrust, hypertrophic cardiomyopathy, long Q T syndrome, Mayo Clinic Center for Regenerative Medicine, Michael Ackerman, People, Research, Stem cell research, sudden cardiac death

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Using stem cells to find causes and treatments to prevent ...

Cardiac Stem Cells Comments Off on Using stem cells to find causes and treatments to prevent … | August 15th, 2020

"You start to feel like there's this temptation of fate," she said. "Once your allusion of permanence is shattered, you feel like anything could happen."

But it was exactly this that made her want to go through with it. After planning so many funerals, going to the hospital to give bone marrow that would help a young boy and his family seemed the right thing to do.

Losing time with her own relatives made her adamant about the ability to help give more time to someone else.

In June, she underwent physical tests and surgery to extract the bone marrow. She felt mostly OK like she had fallen on ice and "got out of laundry for a few days." She knows she can't speak for all donors, but for her, it was a fairly swift recovery.

She thought of the child's family. She remembered her four children at age 7.

"I remember how little they were," she said. "You just want to protect them."

She doesn't know anything more about the boy, and DMKS can't release more information because of privacy laws. His family can reach out to her, but Leone says she's not expecting any communication because she is sure they have plenty going on with him undergoing treatment.

But she isn't seeking gratitude. In fact, she feels she has been given a gift. The thought that perhaps she is able to help is a bright spot in a tough year.

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Chicago mom of 4 donates bone marrow to 7-year-old boy she doesn't know. 'You just want to protect them.' - Herald & Review

Bone Marrow Stem Cells Comments Off on Chicago mom of 4 donates bone marrow to 7-year-old boy she doesn’t know. ‘You just want to protect them.’ – Herald & Review | August 13th, 2020

New Jersey, United States,- Verified Market Researchhas recently published an extensive report on the Stem Cell Therapy Market to its ever-expanding research database. The report provides an in-depth analysis of the market size, growth, and share of the Stem Cell Therapy Market and the leading companies associated with it. The report also discusses technologies, product developments, key trends, market drivers and restraints, challenges, and opportunities. It provides an accurate forecast until 2027. The research report is examined and validated by industry professionals and experts.

The report also explores the impact of the COVID-19 pandemic on the segments of the Stem Cell Therapy market and its global scenario. The report analyzes the changing dynamics of the market owing to the pandemic and subsequent regulatory policies and social restrictions. The report also analyses the present and future impact of the pandemic and provides an insight into the post-COVID-19 scenario of the market.

Global Stem Cell Therapy Market was valued at USD 117.66 million in 2019 and is projected to reach USD 255.37 million by 2027, growing at a CAGR of 10.97% from 2020 to 2027.

The report further studies potential alliances such as mergers, acquisitions, joint ventures, product launches, collaborations, and partnerships of the key players and new entrants. The report also studies any development in products, R&D advancements, manufacturing updates, and product research undertaken by the companies.

Leading Key players of Stem Cell Therapy Market are:

Competitive Landscape of the Stem Cell Therapy Market:

The market for the Stem Cell Therapy industry is extremely competitive, with several major players and small scale industries. Adoption of advanced technology and development in production are expected to play a vital role in the growth of the industry. The report also covers their mergers and acquisitions, collaborations, joint ventures, partnerships, product launches, and agreements undertaken in order to gain a substantial market size and a global position.

1.Stem Cell Therapy Market, By Cell Source:

Adipose Tissue-Derived Mesenchymal Stem Cells Bone Marrow-Derived Mesenchymal Stem Cells Cord Blood/Embryonic Stem Cells Other Cell Sources

2.Stem Cell Therapy Market, By Therapeutic Application:

Musculoskeletal Disorders Wounds and Injuries Cardiovascular Diseases Surgeries Gastrointestinal Diseases Other Applications

3.Stem Cell Therapy Market, By Type:

Allogeneic Stem Cell Therapy Market, By Application Musculoskeletal Disorders Wounds and Injuries Surgeries Acute Graft-Versus-Host Disease (AGVHD) Other Applications Autologous Stem Cell Therapy Market, By Application Cardiovascular Diseases Wounds and Injuries Gastrointestinal Diseases Other Applications

Regional Analysis of Stem Cell Therapy Market:

A brief overview of the regional landscape:

From a geographical perspective, the Stem Cell Therapy Market is partitioned into

North Americao U.S.o Canadao MexicoEuropeo Germanyo UKo Franceo Rest of EuropeAsia Pacifico Chinao Japano Indiao Rest of Asia PacificRest of the World

Key coverage of the report:

Other important inclusions in Stem Cell Therapy Market:

About us:

Verified Market Research is a leading Global Research and Consulting firm servicing over 5000+ customers. Verified Market Research provides advanced analytical research solutions while offering information enriched research studies. We offer insight into strategic and growth analyses, Data necessary to achieve corporate goals, and critical revenue decisions.

Our 250 Analysts and SMEs offer a high level of expertise in data collection and governance use industrial techniques to collect and analyze data on more than 15,000 high impact and niche markets. Our analysts are trained to combine modern data collection techniques, superior research methodology, expertise, and years of collective experience to produce informative and accurate research.

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Stem Cell Therapy Market Size by Top Companies, Regions, Types and Application, End Users and Forecast to 2027 - Bulletin Line

Bone Marrow Stem Cells Comments Off on Stem Cell Therapy Market Size by Top Companies, Regions, Types and Application, End Users and Forecast to 2027 – Bulletin Line | August 13th, 2020

Unlike other CAR T-cell therapies, clinical success was not associated with significant complications from therapy, said Dr. Jonathan Serody. This means this treatment should be available to patients in a clinic setting and would not require patients to be hospitalized, which is critical in our current environment.

Results from the parallel phase 1 and phase 2 studies also demonstrated that the CAR T-cell therapy was safe and did not produce any serious or severe side effects.

Researchers from the UNC Lineberger Comprehensive Cancer Center and Baylor College of Medicine administered anti-CD30 CAR T cells to 41 patients with relapsed or refractory Hodgkin lymphoma. All patients underwent lymphodepletion with bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine prior to the anti-CD30 CAR T-cell therapy.

Measuring safety was the primary goal of the two parallel studies.

The overall response rate, or the percentage of partial or complete responses to therapy, among 37 evaluable patients was 62%. Thirty-four of the patients received fludarabine-based lymphodepletion 17 of which received it with bendamustine, and the other half received it with cyclophosphamide. Two of these patients were considered to be complete response at infusion and maintained the response, so they were not included in final analysis.

The overall response rate among the remaining patients was 72%, with 59% of patients achieving a complete response. After a median follow-up of 533 days, researchers identified the one-year progression free survival rate to be 36% and the one-year overall survival rate to be 94%.

This is particularly exciting because the majority of these patients had lymphomas that had not responded well to other powerful new therapies, said senior study author Dr. Barbara Savoldo, professor in the Department of Microbiology and Immunology at the UNC School of Medicine, in a press release.Patients within the study had received a median of seven previous lines of therapy that included checkpoint inhibitors and autologous or allogeneic stem cell therapies, therapies known to be powerful but also tend to come with a host of side effects.

However, treatment with the anti-CD30 CART cells demonstrated a favorable safety profile. Although 10 patients developed cytokine release syndrome, all cases were considered minor.

Patients who received fludarabine-containing lymphodepletion were the only participants in the study to have a response to the anti-CD30 CAR T-cell therapy.

Although CD30 CAR T (cells) showed modest activity in (Hodgkin lymphoma) when infused without lymphodepletion, robust clinical responses were achieved when these cells were infused in hosts lymphodepleted with fludarabine-containing regimens, the authors wrote.

The activity of this new therapy is quite remarkable and while we need to confirm these findings in a larger study, this treatment potentially offers a new approach for patients who currently have very limited options to treat their cancer, said Dr. Jonathan Serody, director of the bone marrow transplant and cellular therapy program at UNC Lineberger Comprehensive Cancer Center, in the release. Additionally, unlike other CAR T-cell therapies, clinical success was not associated with significant complications from therapy. This means this treatment should be available to patients in a clinic setting and would not require patients to be hospitalized, which is critical in our current environment.

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Novel CAR T-Cell Therapy Shows Promise in Advanced Hodgkin Lymphoma - Curetoday.com

Bone Marrow Stem Cells Comments Off on Novel CAR T-Cell Therapy Shows Promise in Advanced Hodgkin Lymphoma – Curetoday.com | August 13th, 2020

Jakafi may offer a survival benefit for patients with myelofibrosis and an increased number of circulating blasts, a recent study found.

While the presence of circulation blasts in the blood is considered an important factor in patient prognosis, the impact of bone marrow blasts on survival is not as well defined. To better understand the connection between the amount of blasts found in the blood and bone marrow together, all in regard to patient prognosis, researchers performed a retrospective analysis of 1,316 patients with myelofibrosis, a type of myeloproliferative neoplasm (MPN).

These patients (median age, 66 years), who all presented to the University of Texas MD Anderson Cancer Center in Houston, Texas, from July 1984 and 2018, had to have available circulation blasts in the blood and bone marrow percentages to be included in the analysis. Survival was noted as the time from the date of referral to the date of last follow-up or death, whichever came first. The median follow-up was 27 months.

Among the total, 700 (53%) had 0% circulation blasts in the blood and less than 5% had bone marrow blasts. Of the remaining patients who had 1% or greater circulation blasts in the blood, the range was as follows:

The researchers also found that higher percentages of circulating blasts in the blood had a negative correlation with hemoglobin and platelets, but a positive correlation with white blood cells, age and the presence of symptoms, among other factors.

Out of the total group, 523 patients (44%) received the JAK1/JAK2 inhibitor Jakafi. The authors noted that patients who received this treatment and also had 10% or less blasts, regardless of whether they were in the blood or bone marrow, saw a superior overall survival rate compared to those with similar disease features who did not receive Jakafi.

The studys authors went on to conclude that patients who have circulating blasts in the blood of 4% or more have an unfavorable prognosis; however, Jakafi offers a significant survival benefit to patients with circulating blasts in the blood of 10% or less, making a combination approach to treatment vital in improving the outcomes of patients with myelofibrosis.

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Jakafi May Offer Survival Benefit in Subset of Patients with Myelofibrosis - Curetoday.com

Bone Marrow Stem Cells Comments Off on Jakafi May Offer Survival Benefit in Subset of Patients with Myelofibrosis – Curetoday.com | August 13th, 2020

Poverty, Government apathy and Covid-19 induced-lockdown restricting travel proved fatal for little Kishan, a 11-year-old boy suffering from Aplastic anemia, a life-threatening blood disorder condition in which the bone marrow and stem cells do not produce enough blood cells

Facing severe financial constraints and waiting timely medical aid, first at Safdarjung Hospital and then AIIMS, both Government hospitals in Delhi, Kishans life was cut short in March this year amid Covid-19 pandemic.

However, Kishans is not a lone case. Dr Nita Radhakrishnan, paediatric haemato-oncologist at Super Speciality Paediatric Hospital, Noida, Uttar Pradesh says that as the deadly Coronavirus captured the attention of the nation in the most unprecedented manner, the non-Covid patients particularly those with the Aplastic anemia have suffered the most in the crisis.

She gave instances of her two teenage patients who succumbed to blood disorder in the Covid catastrophe. Manish (name change), a 17-year-old was suffering with on-and-off fever, gum bleeding, and melena for three months, he came to us in December last year just when Coronavirus had started spreading its tentacles from China to other parts of the world.

The boy was diagnosed with severe Aplastic anemia and was recommended requisite treatment like regular hospital visit for red cell transfusion before he could be given bone marrow transplant (BMT), a life saving treatment.

However, while the family was not able to visit our hospital in Noida due to the covid-lockdown, no blood products were available at the hospital near to the patients locality. In want of blood, Manish could not survive more days.

13-year-old Suresh (name change) too faced similar fate. While Government funds could not be sanctioned for his BMT in time the boy could not visit the Noida hospital for further follow-up due to travel restrictions. Two weeks later, Suresh died due to hemorrhage at his native place, lamented the doctor.

These are just two reported cases from the NCR hospital located near the countrys capital. Several have gone unreported. The Government has no policy nor any long-term plan for such patients.

The prognosis of severe aplastic anemia in our country is dismal. The incidence of 46 per million population of childhood aplastic anemia in India and other Asian countries is higher than what is observed in the West, explains Dr Radhakrishnan. The scenario is gloomy for the patients afflicted with the disease as they need blood transfusion almost every 20 days.

A significant proportion of patients of aplastic anemia (around 30 per cent) die before any definitive treatment is initiated. A study by AIIMS based on a recent series of patients follow-up showed that out of 1501 patients diagnosed over last seven years, only 303 ie 20 per cent received the definitive treatment modalities through either BMT or IST with ATG and cyclosporine, says Dr Radhakrishnan in her case report Aplastic anemia: Non-COVID casualties in the Covid-19 era, published in the latest edition of Indian Journal of Palliative Care.

The doctors have sought urgent intervention. Dr Radhakrishnan says that as we await the peak of Covid-19 in our country and possibly secondary and tertiary waves thereafter, patients with aplastic anemia who are the sickest among all hematological illnesses would benefit greatly from urgent intervention from the Government to ensure timely treatment.

Those suffering with Aplastic anemia, there is mostly delay in diagnosis, delay in initiation of treatment due to monetary constraints, non-inclusion of the disease under government schemes such as Ayushman Bharat and NHM and delay in sanction of money from other Government schemes such as Rashtriya Arogya Nidhi, Chief Minister and Prime Ministers relief fund often due to lack of proper documents, she added.

Delay means, risk of contracting fungal infections and increase in drug-resistant bacterial infections increase which further hamper the treatment, point out Dr Ravi Shankar and Dr Savitri Singh in the study.

Though the Union Health Ministry, after few days of lockdown period, issued directions for continuing treatment for essential health services including reproductive and maternal health services, newborn care, severe malnutrition, and NCDs including cancer care, palliative care, dialysis, and care of disabled, unfortunately those with Aplastic anemia got ignored.

This despite of the fact that these patients are at the highest risk of death following a break in the treatment of few weeks, notes Dr Radhakrishnan.

Because of the closure of offices and absence of staff, during the lockdown period, there was delay in sanction of usual grants due to the lockdown of offices and inability in generating documents such as income certificate from the tehsils.

For instance, Suresh and Manish, both our patients received the Government grant after around 34 months of applying for the same. But both had died before they could reach the hospital for treatment, lamented the hematologist.

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Covid-19 Impact: Patients with aplastic anemia at receiving end - Daily Pioneer

Bone Marrow Stem Cells Comments Off on Covid-19 Impact: Patients with aplastic anemia at receiving end – Daily Pioneer | August 13th, 2020

INTRODUCTION

The ability to regenerate complex body parts varies considerably in the animal kingdom. While planarian and hydra are able to regenerate their entire bodies, many avian and mammalian species mostly stop at the wound healing stage without a reparative regeneration process (1). This disparity may result from complexity differences among organisms by nature, yet it leaves us the hope that we may learn from highly regenerative species to improve our own regenerative potential.

Zebrafish is known for its ability to regenerate multiple complex body structures (2). Among regenerable tissues, the caudal fin serves as a great model due to its faithful and rapid regeneration, ease of manipulation, and relatively low complexity. A key step in regeneration is the formation of the blastema, a layer of proliferative and undifferentiated cells that accumulates between the wound site and the wound epidermis following initial wound closure. This step occurs in response to appendage loss and is one of the key features that separates regenerative systems from nonregenerative systems. At later stages of regeneration, the blastema further proliferates and differentiates to regenerate the missing complex structures.

However, the molecular signatures of blastemal cell state transitions during regeneration in zebrafish remain elusive. The state of a cell can be represented by its collective gene expression profile, which has only been measured in bulk for all genes or in specific lineages of cells for a subset of genes during caudal fin regeneration. Prior work has shown that both proliferation of progenitors and dedifferentiation of adult lineage cells contribute to the blastema (38). Progenitors respond to injury cue and proliferate as in normal development. Cells derived from mature adult lineages, however, lose their lineage-specific markers while obtaining progenitor-like markers when they proliferate. Neither type of cell gains multipotency, but rather, they proliferate and regenerate with lineage restrictions. The limited resolution and throughput of these approaches have prevented a more systematic understanding of blastema cells. The advent of single-cell transcriptomic technologies promises to reveal signals masked at the bulk tissue level (9), granting us an opportunity to define and monitor cellular state transition in regenerating fin at an unprecedented resolution.

In this study, we generated single-cell transcriptomic maps of regenerating fin tissue. These maps allowed us to separate the contribution from different cell types and track the transcriptomic dynamics in cell state transitions during regeneration. By comparing with the profiles obtained from uninjured fin tissue, we identified cell types involved in regeneration. We demonstrated the activation of cell cyclerelated programs shared across cell types as well as cell typespecific programs. Furthermore, we defined the heterogeneity in both epithelial and blastemal populations and their functional relations to the regeneration process.

To better understand cell type involvement in fin regeneration, we characterized single-cell transcriptional landscapes for both preinjury and regenerating caudal fin tissues using the 10x Genomics platform (see Materials and Methods and table S1) (9). We sampled regenerating fins from 1, 2, and 4 days post-amputation (dpa) time points to interrogate the stages of blastema formation, outgrowth, and maintenance (Fig. 1A). Fin samples were collected from multiple fish to control for individual variation while at the same position along the proximal-distal axis to avoid positional effects. To establish the transcriptional ground states for each cell type in the fin tissue, we first focused on cells collected from the preinjury time point. Via an unsupervised clustering of 4134 cells, we identified epithelial cells (epcam and cdh1), hematopoietic cells (mpeg1.1 and cxcr3.2), and mesenchymal cells (msx1b and twist1a) (fig. S1, A and B) (1014). Epithelial cells are from three transcriptionally distinct subgroups, representing the superficial (krt4), intermediate (tp63), and basal layers (tp63 and krtt1c19e) of the epithelium (fig. S1, A and B) (15, 16).

(A) General experimental design. Zebrafish caudal fin tissues at preinjury and 1/2/4 dpa stages were collected. (B) Clustering assignments for caudal fin cells collected from each stage. Uniform Manifold Approximation and Projection (UMAP) axes were calculated from the integrated cells dataset as in (C). (C) Clustering assignments for caudal fin cells collected from both preinjury and regenerating stages. Cells were plotted on UMAP axes. Color coding is the same as in (E). (D) Percentage distribution of the major cell types captured in caudal fin, grouped by their stage of collection. Color coding is the same as in (E). (E) Differential expressions of the key marker genes by the identified major cell types. Color gradient: normalized relative expression level. Dot size: percentage of cells in the cluster that express the specified gene.

To determine whether the same cell types existed in the regenerating stages, we performed analysis using two different approaches: (i) Cells from each stage were clustered independently, and (ii) cells from both uninjured fins and injured fins were integrated through the anchoring approach (see Materials and Methods; Fig. 1, B, C, and E; and table S2) (17). For both approaches, we regressed out cell cycle effects before principal components analysis (PCA). Agreement between cluster assignments was measured using Hubert and Arabies adjusted Rand index (ARI). An average ARI of 0.86 (preinjury, 0.86; 1 dpa, 0.85; 2 dpa, 0.90; and 4 dpa, 0.83) indicated that clustering results generated using the two approaches were highly consistent. Cell types identified in the preinjury cells presented consistently across all regenerating stages, suggesting that regenerating fins contain the same cell types as the preinjury fins.

New regenerates are built up by the proliferation and migration of cells located at a number of fin segments away from the amputation plane (2). In response to injury cues, these cells gained the ability to detach from local tissue, enter cell cycle, and migrate toward the wound site while undergoing transcriptional reprogramming. We computationally separated S phase, G2-M phase, and G1-phase cells based on the expression level of cell cyclerelated genes and performed clustering analysis using only S phase cells (see Materials and Methods and fig. S2A). In this cycling cell population, we identified epithelial, mesenchymal, and hematopoietic cell groups as before (Fig. 2, A to C, and table S3). Our data support a model in which cells likely keep their original identities during proliferation.

(A) Cell type clustering of S phase cells plotted onto UMAP axes calculated by S phase cell only. Cells are colored by the general cell types merged from major cells types in Fig. 1B. (B) Stage distribution of S phase cells. Cells were plotted on the same UMAP axes as in (A) and colored by stage when the cells were collected. (C) Relative expression levels of the top 30 differentially expressed genes from each cluster of only S phase cells. (D) Venn diagrams of numbers of genes shared between the cell cycleactivated genetic programs. Left, included all genes; right, included only cell cyclerelated genes (see Materials and Methods).

Next, we asked whether different regenerating cell types exhibited similar or distinct cell cycle regulations. To this end, we identified genes up-regulated in S phase cells compared to G1 phase cells in each cell type, respectively (logFC, >0.25; minimum percentage, >10%). Of the 1098 differentially expressed genes, 161 were shared across all three groups of comparisons (Fig. 2D and table S4). Of these shared genes, at least 54 genes were related to cell cycle regulation, underscoring a shared program governing cell cycle reentry (criteria described in Materials and Methods). In contrast, hundreds of genes differentially highly expressed in S phase exhibited cell typespecific pattern, of which dozens were related to cell cycle (Fig. 2D). We next evaluated the degree of conservation of these enriched genes by asking what fraction did not have human orthologs that had been curated in the Metascape database (18). Twenty-five percent of genes in the epithelial cellspecific group had no human ortholog, whereas all shared groups had at most 15% genes without a human ortholog, suggesting that enriched genes shared by cell types were more evolutionarily conserved (fig. S2C).

Some cell typespecific S-G1 enriched genes were also expressed in a cell typespecific manner regardless of their cell cycle phases: For example, psmb8a and psmb9a shared similar epithelial-hematopoietic enrichments (fig. S2D). The human homologs of these genes (PSMB8 and PSMB9) encode 5i and 1i subunits of the immunoproteasome (19). Together with 2i and PA28 subunits of the proteasome, they turn the proteasome into immunoproteasome and take part in immune response (20). Immunoproteasome digests peptides more efficiently, promoting antigen presentation by a major histocompatibility complex (MHC) class I molecule. Although they did not pass the differential expression criteria in the S-G1 comparison, zebrafish psmb10, psme1, and psme2 shared a differential expression signature similar to that of psmb8a and psmb9a, suggesting that zebrafish might use the same group of subunits for the assembly of immunoproteasomes that might help increase immune responses during regeneration, especially in epithelial and hematopoietic cells (fig. S2, D and E). In addition, we found three genes that shared the same expression signature with the immunoproteasome subunits (psmb13a, psmb12, and psma6l) (fig. S2E) without known human or mouse homologs, suggesting that they might form zebrafish-specific proteasomes with functional relevance to regeneration (19).

Consistent with current knowledge, we observed three transcriptionally distinct subgroups in the preinjury epcam+ epithelial cells, representing the superficial, intermediate, and basal layers of the adult zebrafish epithelium (Fig. 3A and fig. S1B) (15, 16). By integrating cells from all stages during regeneration, we found clusters of cells that corresponded to all three layers of the epithelium after injury (Fig. 1, B and C). In addition, we captured a rare agr2+ population (referred to as mucosal-like epithelium herein) that was too small to be clustered by itself in the preinjury stage (Fig. 1E). These cells shared general epithelial features with the other epithelial layers but exhibited higher expression of a unique set of 200 genes. We examined the expression distribution of the orthologs of these genes in human tissues (The Human Protein Atlas, http://proteinatlas.org/) (21). Among the top 30 genes with human orthologs, 11 showed enriched expressions in proximal digestive or gastrointestinal tract and another 11 in bone marrow of blood lineages, suggesting that this population is analogous to cells in the mucosa in mammalian systems (table S2). In zebrafish, agr2 is required for the differentiation of the mucosal-producing goblet cells in the intestinal epithelium (22). To confirm the cell typespecific expression pattern of this gene in the fin tissue, we performed in situ hybridization on agr2 in both uninjured and regenerating fin tissues (see Materials and Methods). agr2 transcripts are scattered within the epithelium regardless of the sample collection stage and reflect a round morphology of the cell expressing it (fig. S3, A, C, E, and G to I). A proportion of agr2+ cells overlap with positive dark blue staining of Alcian blue in serial sections, suggesting that these cells are mucous cells that are known to exist in the caudal fin epithelium (fig. S3, B, D, and F) (23).

(A) Diagram of the stratified adult zebrafish epithelium. (B) Differential expressions of claudin family and keratin family genes in epithelial subgroups shown as a dot plot. Known epithelial markers krt4, fn1b, tp63, and krtt1c19e were included for comparison. Cells were first grouped by major cell types and then separated into preinjury and regenerating stages. Darkness of dot color: relative expression level. Dot size: percentage of cells in the cluster that express the specified gene. (C) In situ hybridization targeting krt1-19d, cldna, cldn1, and krt4 of 4-dpa fin tissues. Brown dots indicate positive RNA signals from target genes, while pale blue blocks represent hematoxylin-stained cell nuclei. Zoomed-in views are presented. Original images can be found in fig. S4. All epithelial layers are above the black dotted lines. (D) Clustering assignment of epithelial cells plotted on UMAP axes calculated with only epithelial cells. Cells are colored by their epithelial layer identity as in (A). (E) The same UMAP visualization as in (D), with cells colored by stage of collection. Arrows connect the groups of comparison, with a direction from preinjury stage to regenerating stages (1, 2, and 4 dpa). Numbers next to the green triangle: number of genes up-regulated in regenerating stage. Numbers next to the red triangle: number of genes down-regulated in regenerating stage. (F) Clustered GO enrichment for genes up-regulated in regenerating basal, intermediate, and superficial epithelial cells comparing to their preinjury counterparts. GTPase, guanosine triphosphatase; ER, endoplasmic reticulum; PKN, protein kinases N; snRNP, small nuclear ribonucleoprotein.

Although the same three-layer classification of epithelial cells could be defined when cells from regenerating stages were integrated with the preinjury cells, the expression of the commonly used layer-specific marker genes changed dramatically during regeneration: Superficial epithelial marker krt4 expanded into basal and intermediate layers of the epithelium, the intermediate layer marker fn1b was also highly expressed in the basal layer, and the basal epithelial marker krtt1c19e was barely detectable in the postinjury cell populations (Fig. 3B) (15, 16). To better understand the molecular features of the epithelial populations, we identified genes significantly more highly expressed in epithelial cells than in hematopoietic and mesenchymal cells and found that cell-cell junction genes ranked high in the list. Among these, genes from the claudin and keratin families were detected at a ratio 20-fold higher than that in randomly selected detectable genes (2 test, P value of <0.0001). We focused on expression patterns of all claudin and keratin genes in zebrafish and found that cldne, cldnf, krt1-19d, and krt17 labeled the superficial cluster; cldnh labeled the mucosal-like cluster; cldna, krt93, and krt94 labeled the intermediate cluster; and cldn1 and cldni labeled the basal cluster (Fig. 3B). Claudin genes are expressed in a tissue-specific manner in zebrafish and are generally considered to be the proteins responsible for regulating the paracellular permeability in the vertebrate epithelium (24). Their differential expression signature in both uninjured and regenerating tissues suggests that they might play important roles in maintaining the permeability in each epithelial population. On the other hand, the expression of keratin genes displayed less restriction across the three layers relative to claudin genes but stronger dependence on regenerating states (Fig. 3B). The differential expression signature suggests that they might perform epithelial subtyperelated function in regeneration. To verify their expression pattern, we performed RNA in situ hybridization targeting the known marker krt4 and new candidates, including krt1-19d, cldna, and cldn1 (Fig. 3C) as well as cldne, krt94, and cldni (fig. S4, A to H). Comparing with the known marker krt4, these genes exhibited more restricted expression patterns in epithelial layers, better representing the molecular signatures of different epithelial populations in the fin tissue regardless of regeneration status (Fig. 3, B and C).

The three epithelial layers were present across the regeneration stages albeit with varying proportions (Fig. 1D). The proportion of basal epithelial cells peaked at 2 dpa, reaching up to 42%, whereas the superficial layer epithelial cells decreased from 27 to 6% at 2 dpa (the coefficient of variations of cell proportions between biological replicates is below 15%). The observed compositional change of the two epithelial populations is consistent with a previous finding that the initial migration of superficial layer cells to the new regenerates is followed by replenishment by basal epithelial cells (25). This basal replenishment was also reflected in the two-dimensional Uniform Manifold Approximation and Projection (UMAP) calculation from only epithelial cells, in which preinjury cells were separated by their respective layers, whereas regenerating cells were closer in the projection space (Fig. 3, D and E). Superficial layer cells from before and after injury stages were in juxtaposition to each other, consistent with our knowledge that this layer of epithelial cells directly migrates to and covers the wound site (25). On the other hand, basal layer cells from before and after injury stages were more distantly separated, suggesting more dramatic changes between resting and regenerating basal epithelial cells.

To understand the mechanisms of epithelium regeneration, we compared the transcriptome between preinjury and regenerating cells for the three epithelial layers. Basal layer cells up-regulated 1271 genes and down-regulated 198 genes during regeneration; both were the highest numbers across all comparisons (numbers of differentially expressed genes were from Wilcoxon rank sum test, adjusted P value of < 0.01; Fig. 3E). We performed gene ontology (GO) enrichment analysis on genes up-regulated in the regenerating stage by layer and found both common and layer-specific programs associated with regeneration (18). All three layers were enriched for oxidative phosphorylation (dre00190), proteasome (dre03050), and cell redox homeostasis (GO:0045454). While basal and intermediate layer cells could be regulated by Rho guanosine triphosphatasemediated Wnt signaling for extracellular matrix organization and actin filament depolymerization, respectively (R-DRE-195258, R-DRE-5625740, R-DRE-195721, GO:0030198, and GO:0030042), superficial layer cells showed enrichment mainly for general transcriptional and translational regulations (Fig. 3F). When comparing the expression profiles between regenerating superficial epithelial and basal epithelial, we saw enrichment for antigen presentation and apoptosis features in the superficial layer (table S5). In addition, the superficial layer contained the lowest proportion of cells in S phase or G2-M phase, further supporting that superficial layer epithelium was most likely maintained by migration and proliferation from other layers (fig. S2B).

Subcluster identification within regenerating basal epithelial cells revealed two subgroups that represented different functionalities during regeneration, one labeled by distally distributed fgf24, while the other by proximally distributed lef1 (fig. S5, A to C) (26, 27). We compared expression profiles between group I (distal) and group II (proximal) cells and found that their suggested functionalities were consistent with their expected roles in regeneration: The distal subgroup (or distal wound epidermis) up-regulated genes associated with extracellular matrix degradation, and the proximal subgroup (or proximal wound epidermis) up-regulated genes associated with organization of extracellular matrix, skeletal system development, and negative regulation of locomotion (fig. S5, D and E). In addition, the increase of proximal cell proportion was accompanied by the decrease of distal cell proportion, suggesting that basal layer epithelium become gradually active in promoting blastema proliferation and differentiation during the initial regeneration process (fig. S5C). To confirm the distribution of these cells, we performed RNA in situ hybridization targeting two candidate genes, stmn1b and sema3b, one from each cluster. The expression of stmn1b was first observed at the basal layer of the wound epidermis at 1 dpa but diminished as regeneration proceeded (fig. S4, I to K). On the contrary, sema3b showed expression at later stages and was enriched in the relatively proximal portion of the basal layer epithelium (fig. S4, L to N). The expression dynamics of these two genes matched the predicted proportion changes of the two clusters (fig. S5C). While sema3b was more restricted to the basal layer, stmn1b showed low expression levels in the intermediate layer as well, potentially suggesting that this subpopulation could be labeling cells transitioning from the basal layer to the other layers of epithelium.

We next performed subcluster analysis within the hematopoietic cluster and found four subpopulations (Fig. 4, A to C and table S6). The first three populations were enriched for the macrophage marker mpeg1.1, with the cluster H1 being M1-like (lgals2+ and lcp1+) and the cluster H3 M2-like (ctsc+ and lgmn+) (Fig. 4D) (12). We speculated that the cluster H2 represented a transition state between M1-like and M2-like or a state before the macrophages differentiate toward M1-like or M2-like. From 1 to 4 dpa, the proportion of M1-like macrophages remained at a constant level, while that of M2-like macrophages expanded (Fig. 4B), potentially suggesting a shift in the function of macrophages in the new regenerates from pro-inflammatory toward anti-inflammatory as regeneration proceeded. Macrophages are important for proper blastema proliferation (28). The change in the proportions of M1/M2-like macrophage in our data matched with that observed in the larvae fin, suggesting that the adults followed a similar rule for immune cell recruitment after injury.

(A) Subcluster assignments of the hematopoietic cells. Cells were plotted on UMAP axes. The same color code is used for (B) to (D). (B) Proportion of subgroups of hematopoietic cells. (C) Expression enrichment of the top 30 differentially expressed genes in the four subclusters within hematopoietic cluster shown as a heatmap. (D) Expression distribution of genes associated with macrophage activation grouped by subclusters. Expression levels were log normalized by Seurat. y axis: cluster identity. z axis: cell density. (E) Expressions of pigment cell markers gch2 and mlpha in the hematopoietic population.

The cluster H4 enriched for genes including mlpha and gch2, both well-characterized markers for the chromatophore lineages in zebrafish (Fig. 4E) (29). Chromatophores are derived from neural crest lineage, yet here, they clustered with macrophages that were from hematopoietic lineage. One possibility is that this clustering result could be driven by features related to antigen presentation via MHC class II, a feature of pigment cells based on studies using human melanocytes (30). The proportion of this cluster decreased as regeneration started, agreeing with the known pattern of fin stripe recovery after amputation (Fig. 4B) (31).

To understand the component and function of the cells in the mesenchymal cell cluster before and during fin regeneration, we focused on genes enriched in this cluster and found previously identified blastema marker genes that are required for fin regeneration, including the muscle segment homeobox family members msx1b and msx3 and the insulin-like growth factor signaling ligand igf2b (logFC, >0.25; minimum percentage, >25%; and adjusted P value of <1 105, as listed in table S1) (2, 13). The mesenchymal cluster expressed these genes nearly exclusively, confirming their blastema identity in regenerating stages (fig. S6A). In addition, we found key genes involved in zebrafish bone development and regeneration: twist1a, the transcription factor that controls the skeletal development by regulating the expression of runx2 (14); cx43, the gap junction protein required for building the fin ray up to the right length; and hapln1a and serpinh1b, two genes downstream of cx43 (32, 33). By performing conserved marker analysis using Seurat, we found that msx1b and twist1a were also among the markers conserved across all stages, underscoring shared features that existed between regenerating and preinjury mesenchymal cells (maximum P values across stages: 4.72 1010 and 2.84 109 for msx1b and twist1a, respectively). This theme of building and supporting bone tissues in mesenchymal cells was not only reflected by a handful of genes: GO analysis of all the detected up-regulated genes in this cluster revealed significant enrichment of genes associated with GO terms, including fin regeneration (GO:0031101) and skeletal system development (GO:0001501) (fig. S6B). When more stringent criteria for differential expression were used, genes were also significantly enriched for GO terms, including skeletal system morphogenesis (GO:0048705) and extracellular matrix organization (GO:0030198) (fig. S6C).

Previous work has shown that blastema comprises bone cells and non-bone cells but has not defined the cell types and the regeneration process of each type (23, 34, 35). To better understand the regeneration process by cell type, we performed clustering analysis within the mesenchymal cluster and identified nine distinct subgroups (Fig. 5A and fig. S6D). Of the two preinjury subgroups, M-2 represented the mature bone lineage, which was enriched for expressions of bglap, mgp, and sost (fig. S6E) (36, 37). Comparing to M-2, cluster M-1 presented low expression levels of bglap, mgp, and sost and high expression levels of a group of other genes, including fhl1a, fhl2a, and tagln (fig. S6E). Mammalian orthologs of these genes are required for chondrogenesis and osteogenesis, leading us to speculate that cluster M-1 could represent the supporting non-bone cell lineage in the preinjury state (38, 39).

(A) Subclustering assignments of mesenchymal cells shown on UMAP axes. Cells are colored by their cluster assignments and connected by Slingshot-reconstructed trajectories. Lineage 1: 1-2-3-4; lineage 2: 1-2-3-5-6; lineage 3: 1-2-3-5-7-8; lineage 4: 1-2-3-5-9. (B) By-lineage highlighting of mesenchymal cells. Cells with colors other than gray represent the cells included in each corresponding lineage in (A). (C) Expression distribution of genes labeling cell lineages and cell states in mesenchymal cells. Gene feature plots were connected by estimated lineages using the same lineage color code as in (A). (D to G) In situ hybridization targeting the tnfaip6 gene in (D) preinjury, (E) 1-dpa, and [(F) and (G)] 4-dpa fin tissues. Brown dots indicate positive RNA signals from target genes, while pale blue blocks represent hematoxylin-stained cell nuclei. A zoomed-in view for the region inside the focused rectangle is provided within (D). (G) Zoomed-in view for the region highlighted by a rectangle in (F). Dotted lines indicate the amputation plane. All scale bars, 100 m.

The remaining seven populations came from regenerates. Pseudotime analysis via Slingshot (40) suggested that these subgroups formed four trajectories, all initiated from the tnfaip6+ cluster (M-3), which was composed mainly of 1-dpa cells (Fig. 5, B and C, and fig. S6D). tnfaip6 was ranked top by an adjusted P value in the differentially expressed genes labeling the regeneration initiation cluster and was also expressed exclusively in the mesenchymal cluster (Fig. 5C and fig. S6A). The mammalian ortholog of this gene is required for proliferation and proper differentiation of mesenchymal stem cells (MSCs) and balances the mineralization via osteogenesis inhibitions (41). The expression of tnfaip6 in the postinjury zebrafish fin suggested that it could also be required in the early stages of regeneration for promoting mesenchymal proliferation. To confirm the expression pattern of tnfaip6, we performed RNA in situ hybridization for uninjured and regenerating fin tissues targeting this gene (Fig. 5, D and E). In the uninjured fin, tnfaip6 was expressed in a segmental pattern, presumably enriching at joints between bone segments. At 1 dpa, tnfaip6 was expressed not only near the bony rays but also in the cavity, showing a general activation in the mesenchymal population. As regeneration proceeded from 1 to 4 dpa, mesenchymal cells divided into cdh11+ (M-4) and tph1b+ (M-5) branches, with the latter further divided into mmp13a+ (M-6), tagln+ (M-7), and vcanb+ (M-9) branches (Fig. 5C and fig. S6D). The mmp13+ (M-6) cluster maintained a high-level tnfaip6 expression, whereas all other branches had a lower but detectable tnfaip6 expression. This was consistent with the observation we made from in situ hybridization at 4 dpa targeting tnfaip6: the broad expression in the mesenchymal population and segmental enrichments similar to that in the uninjured fin (Fig. 5, F and G).

The four trajectories initiated from the tnfaip6+ cluster revealed four putative lineages representing bone and non-bone cells in the blastema. cdh11+ lineage 1 specifically expressed runx2 and osterix/sp7, which are the key transcription factors regulating osteogenesis (fig. S6E) (42). Mammalian ortholog of cdh11 could induce Sp7-dependent bone and cartilage formation in vivo, suggesting that the cdh11+ branch in the blastema represented the regenerating osteoblasts (43). Genes highly expressed at the end of this lineage (M-4) compared to the initiation point (M-3) were associated with bone mineralization and skeletal system development, further supporting their bone cell identity (table S7).

Mesenchymal cells outside the osteoblast branch shared enrichment for tph1b and aldh1a2 expressions at 2 dpa, followed by and1 expression at 4 dpa (Fig. 5C and fig. S6F). These three genes had been suggested to label joint fibroblasts, fibroblast-derived blastema cells, and actinotrichia-forming cells in the blastema, respectively (34, 35, 44). However, their expression signatures implied that instead of labeling separate populations in the blastema, they might be labeling different states of the same non-osteoblastic cells at the early stage of fin regeneration.

Upon 4 dpa, these non-osteoblastic cells diverged into three groups (Fig. 5C and fig. S6D). To understand this separation, we performed differential expression analysis for each branch between cells at the end of the lineage tree (lineage 1, M-4; lineage 2, M-6; lineage 3, M-7 and M-8; and lineage 4, M-9) and cells in the initiation cluster (M-3). Genes highly expressed at the lineage end points were included for GO analysis for functional predictions (logFC, >0.25; minimum percentage of >25%; and adjusted P value of <0.01). These three lineages were also associated with skeletal system development or extracellular matrix organizations as were the bone cell lineage; however, the association was driven by a nearly completely different set of genes (table S7). Unlike the osteoblast lineage, none of these three non-bone cell lineages showed enrichment for bone mineralization, suggesting that these cells might indirectly contribute to bone formation. In lineage 2, top differentially expressed genes mmp13a and ogn both have mammalian orthologs that are associated with bone formation (Fig. 5C and fig. S6F) (45, 46). In addition, this lineage presented up-regulation of DLX family genes, especially dlx5a, suggesting the reactivation of fin outgrowthrelated developmental programs during regeneration (fig. S6F and table S7) (47). Lineages 3 and 4 both enriched for estrogen response and expressed the retinoic acid (RA) synthesis gene aldh1a2. However, only lineage 3 displayed up-regulation of the RA-degrading enzyme cyp26b1 (fig. S6F and table S7). The cyp26b1high-aldh1a2low pattern helped to reduce RA levels in the blastema, promoting redifferentiation of the osteoblasts (44). The differentiation-promoting signature was also reflected in the enrichment of genes, including col6a1 and tagln, whose mammalian orthologs are essential for bone formation (fig. S6F and table S7) (39, 48). These genes were also enriched in the preinjury non-bone cell population, suggesting a connection between this subset of the non-bone cells and their preinjury counterparts (Fig. 5C and fig. S6F). Top up-regulated genes in lineage 4, on the other hand, were main contributors of the extracellular matrix, including and1/2, loxa, and vcanb (35, 49, 50). Enriched expression of these genes suggested that this lineage could be responsible for creating and organizing the fibrous environment. Together, the various non-osteoblastic cells could potentially work collaboratively with the osteoblasts in creating the environment for bone tissue regeneration.

Genes that had been suggested to label progenitors contributing to fin regeneration (mmp9 and cxcl12a) and several orthologs of known mammalian MSC markers (lrrc15, prrx1a/b, and pdgfra) (6, 7, 51, 52) were expressed almost exclusively in the mesenchymal cluster (fig. S6A). Consistent with the observations made in the lineage-tracing study, the mmp9 expression was associated with the regenerating bone cell lineage (lineage 1; Fig. 5B and fig. S6E) (7). However, mmp9 was detected only in a small portion of the mesenchymal cells and was highly expressed in the basal epithelium cells at similar proportions. On the other hand, we observed coenrichment of cxcl12a (previously known as sdf-1) and orthologs of the known mammalian MSC markers in the preinjury population (fig. S6E). cxcl12a-expressing cells in zebrafish were found to carry osteogenic, adipogenic, and chondrogenic characteristics in vitro like MSCs would do and contributed to the mesenchyme of the newly developing bony rays during fin regeneration (6, 53). The coenrichment pattern suggested that some of the preinjury cxcl12a-expressing cells could be MSCs in the fin tissue, which contribute to fin regeneration.

Zebrafish caudal fin is a unique regeneration system to model the injury response and regeneration of vertebrate appendages despite being a simple structure without muscular and adipose tissues. Major components of the regenerating caudal fin are epithelial cells covering the wound site and blastemal cells producing the connective tissue and bone matrices. Early studies established that actively proliferating blastema is the key to regeneration. Formed by cell migration and proliferation, this layer of cells continues in outgrowth and differentiation, rebuilding the complex body structure. Despite efforts in understanding its importance, basic questions regarding the formation of blastema remained: (i) Which type of cells contributes to the blastema and (ii) how do they shape the regeneration process?

Using single-cell transcriptomes, we defined cell types in both preinjury and postinjury fin tissues. Although regenerating cells were drastically different from their preinjury counterparts, both stage-specific and integrated clustering analysis revealed the same major cell type compositions in the fin tissues regardless of their time of collection. Common cell types detected include epithelial cells from all three layers, hematopoietic cells, and mesenchymal cells. Our data lay a foundation for lineage-targeted analysis to investigate the role of epithelial layers and subtypes in fin regeneration.

For each cell type to be a consistent component in the regenerated fin, cell cycle entry is required. We found that both common and unique cell cycle programs activated in the regenerating fin, with the shared ones appearing to be more evolutionarily conserved than the unique ones. Among the genes showing cell typespecific S phase enrichment, several immunoproteasome subunits also showed a clear cell typespecific expression. We speculated that the increasing level of immunoproteasome subunits in epithelial and hematopoietic cells specifically might accelerate antigen processing and presentation, which could be important for immune cell recruitment and tumor necrosis factorinduced blastemal proliferation (54).

Epithelial cells were the most abundant cell type in the profiled fins and could be clustered into four different subgroups, including the three layers in the adult fish epithelium and the mucosal-like cells within the intermediate layer. However, markers labeling these layers did not perform well in separating cell groups when only regenerating cells were considered. An unbiased differential expression test suggested that some members of the krt and cldn families were expressed in specific layers more consistently throughout regeneration. RNA in situ hybridization targeting cldne, krt1-19d, cldna, krt94, cldni, and cldn1 confirmed their exclusive layer-specific expression pattern, underscoring their potential to serve as markers for the distinct epithelial layers during regeneration. Our epithelium-specific analysis suggested that basal layer epithelial cells proliferate and could be the main source for replenishing the other two layers of the epithelium, similar to findings in a previous study based on genetic lineage tracing in zebrafish and echoing findings made using the axolotl limb regeneration model (25, 55). We observed higher apoptosis and lower proliferation features in the superficial epithelial layer compared to the other layers. At the same time, we observed transition patterns in gene expression, connecting the basal to the intermediate and the superficial layer during regeneration.

The behavior of mucosal-like cells during regeneration had been rarely reported for zebrafish in literature. We found in this study that this group of cells was an integral part of the regeneration process. Enrichment of foxp1b in this population and enrichment of foxp4 in basal and intermediate epithelial cells supported that zebrafish foxp homologs could be involved in regulating agr2 expression as does the Fox family in mice and, furthermore, the mucin production in the epithelium during regeneration (Fig. 1E) (56). The protein encoded by amphibian homologs of agr2, nAG (from newts) and aAG (from axolotl), are necessary and sufficient for salamander limb regeneration (57, 58). They are expressed in both dermal glands and the nerve sheaththe pattern of which has also been recovered from single-cell RNA sequencing (scRNA-seq) analysis (55). Regeneration deficiencies caused by denervation before amputation can be rescued by the ectopic expression of nAG. Although we do not have data supporting the nerve sheath expression pattern, as shown for the amphibian models, we hypothesize that agr2 could similarly mediate neuronal signals in zebrafish during regeneration.

Macrophages are critical players in the zebrafish caudal fin regeneration (28, 54). We observed subgroups of the mpeg1.1+ macrophage population in the regenerating fin tissue, resembling M1 and M2 macrophages in mammalian systems. However, we were not able to recover other immune cell population in the hematopoietic cells. This could potentially be due to the systematic bias against certain cell types during tissue dissociation and droplet incorporation in the microfluidic device. The same bias might also explain why we were not able to recover some other known players in the regenerating fin tissue, including neurons and endothelial cells (4). Increasing the number of cells sampled for scRNA-seq or performing scRNA-seq on sorted hematopoietic lineage cells would help to better understand the involvement of these populations in the regeneration process.

The expression profiles of mesenchymal cells captured from the postinjury stages resembled those of blastema in histology studies. We found four connected but distinct lineages representing both bone and non-bone cells in the blastema. All four lineages initiated from one cluster mostly consisted of 1-dpa cells and enriched for the tnfaip6 expression. A similar scenario has been observed in the axolotl limb regeneration model. By using scRNA-seq on a lineage-labeled axolotl model, Gerber et al. (58) found that connective tissue cells funnel into a progenitor state at initiation. Whether the cluster identified in our study represented a shared cell origin for the blastema or a shared state across mesenchymal cell types in the initial blastema-formation stage requires further investigation. High proportion of epithelial population in the fins could also hamper the discovery of relatively rare population with multipotency. Finer dissection before single-cell profiling might help in future study designs in capturing these populations.

While the bone cell lineage has been well studied in the regenerating fin, non-bone cells had been labeled by different markers and given different names and their intercorrelations left to be clarified. We found that tph1b, aldh1a2, and and1/and2 genes were shared among the non-bone cell lineages and could be labeling states instead of types of blastemal cells during regeneration. Meanwhile, differential analysis revealed similar enrichment for bone formation in all lineages yet distinct associations with reactivation of developmental programs, RA signaling, and collagen metabolism, underscoring their collaborative and complementary roles in the regeneration process.

Our scRNA-seq data also provided more details about the fish system we are working with. For all sample collections, we used the transgenic strain Tg(sp7:EGFP)b1212, which specifically labels osteoblast lineage in the fish (59). It was reported that green fluorescence signal could be detected in the fish skin after 72 hours post-fertilization. This ectopic expression, however, does not interfere with confocal imaging of skeletal structures of fish at any stage due to the fact that they lie in different planes of focus. What these cells are and why they expressed the transgene were unclear. In this study, we obtained a holistic view of the transgene expression pattern in the fin region regardless of whether that was associated with the cell type of interest, i.e., osteoblasts in this context. Unsupervised clustering on the expression profiles from single fin cells suggested that green fluorescent protein (GFP) is not only expressed in the mesenchymal but also highly enriched in the superficial layer epithelium (table S2). A closer examination of this classic reporter gene construct revealed that the regulatory region of sp7 used for the construction of the transgene did not exactly represent the endogenous sp7 regulatory region. Tg(sp7:EGFP)b1212 was generated from bacterial artificial chromosome transgenesis using CH73-243G6 as the backbone, which did not contain the first exon of sp7 according to the annotation of the current genome assembly (chr6:58630884-58720045 and GRCz10), leading to the usage of a regulatory sequence different from the endogenous version. Whether this usage difference contributed to the ectopic expression pattern of the transgene requires further study. This finding points to the potential of using single-cellbased approaches in reporter line validation and more thorough analysis of the transgene behavior.

All zebrafish were used in accordance with protocol no. 20190041 approved by the Washington University Institutional Animal Care and Use Committee. Wild-type and Tg(sp7:EGFP) strains are maintained under standard husbandry in the Washington University Fish Facility, with the system water temperature at 28.5C and a day-night cycle controlled as 14-hour light/10-hour dark. For fin amputation, we anesthetized 1-year-old fish with MS-222 (0.16 g/liter) in the system water and then removed the distal half of their caudal fin with sterilized razor blades. The fish were then sent back to circulating water system for recovery. We collected regenerating fin tissue from 39 fish by doing secondary fin amputation at the primary cutting plane with the same anesthesia and recovery procedures.

Collected fin tissues were digested by Accumax (Innovative Cell Technologies), filtered through 40-m cell strainers, and washed with 1 Dulbeccos phosphate-buffered saline (DPBS)0.04% bovine serum albumin to generate single-cell suspensions. Libraries were constructed from these cell suspensions following the instruction of the Chromium Single Cell Gene Expression Solution 3 v2 (10x Genomics) and were subsequently sequenced on HiSeq2500 (Illumina) with read lengths of 26 + 75 (Read1 + Read2). Raw reads were processed by Cell Ranger (10x Genomics) with default parameters for read tagging, alignment to zebrafish reference genome (GRCz10), and feature counting based on Ensembl release 91 (cellranger count). EGFP sequence was added into the reference genome as a separate chromosome for mapping reads from the reporter gene.

We performed unsupervised clustering using Seurat v3.0 following the procedure of normalization (SCTransform), highly variable gene detection, dimensional reduction (principal components analysis), and cells clustering (Louvain clustering at resolutions from 0.1 to 0.6) (17). For integrating the four stages in finding conserved cell types, we used the anchoring approach provided by Seurat v3. Cell clustering was based on the top principal components that account for most of the cell-cell variances. The same set of principal components was used in UMAP calculation for visualization as well.

We found differentially expressed genes in each cluster by comparing the expression profiles of them with those of the rest of the cells using Wilcoxon rank sumbased approach with the criteria of log fold change more than 0.25 and a minimum cell percentage of 0.25. The same criteria were applied to all pairwise comparisons, unless stated otherwise. We made functional connections between the list of differentially expressed genes and the type of cell that they most likely represent by testing for GO term enrichment (18) and manual curation by searching The Zebrafish Information Network database and PubMed. Certain cell clusters were taken as independent samples for secondary clustering following the same unsupervised clustering procedures.

We calculated the by-cell average expression level of a set of S phase or G2-M phase markers suggested by Seurat that are detected in our zebrafish dataset and normalized by subtracting aggregated expression of control genes. Although G1 phase cells are also within cell cycle, they are hardly separable from G0 cells. To avoid false-positive labeling for active cycling cells, we set stringent thresholds and only included cells with |S.score G2M.score| > 0.1 in the S or G2-M group, while cells with both S.score and G2M.score below zero as G1. Other cells were not included in this part of the analysis. Differentially expressed genes were also identified by Wilcoxon rank sumbased approach. These differentially expressed genes were considered to be cell cycle related if they were in the list of genes associated with R-DRE-1640170 Cell Cycle and/or cycling marker genes used for cell cycle phase score calculations.

We collected uninjured and regenerating fin tissues from casper (nacrew2/w2;roya9/a9) fish and fixed in 4% paraformaldehyde overnight (60). Fixed tissues were subsequently submerged in 10% sucrose in 1 PBS, 20% sucrose in 1 PBS, and 30% sucrose in 1 PBS for 4 hours each. After sucrose exchange, tissues were embedded in Optimal Cutting Temperature (O.C.T.) compound (Fisher Healthcare Tissue-Plus) and snap frozen on dry ice. The frozen tissue blocks were then processed into 15-m sections on a Leica CM1950 cryostat. We performed RNA in situ hybridization targeting krt4, cldne, krt1-19d, cldna, krt94, cldni, cldn1, agr2, sema3b, stmn1b, and tnfaip6 for mRNA detection using an RNAscope kit (Advanced Cell Diagnostics, Hayward, CA, USA). Alcian blue/periodic acidSchiff (PAS) staining was subsequently performed on the same section or separately on a consecutive serial section following the manufacturers protocol (Newcomer Supply). Microscopic images were taken by ZEISS Axio Observer.

Cell trajectories were constructed using Slingshot v1.3.1 (40). Through initial subclustering and cell type identifications, we found one subcluster with high epcam expression, potentially a doublet cell contamination from the major cell type classifications. We removed this group of cells from all downstream analysis within the mesenchymal cluster. We used UMAP embedding and subclustering assignments as input for the Slingshot calculation.

We performed nonparametric Wilcoxon rank sum test to identify differentially expressed genes across cell groups as implemented in Seurat. P values were adjusted by all features in the dataset using Bonferroni correction.

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Cellular diversity of the regenerating caudal fin - Science Advances

Bone Marrow Stem Cells Comments Off on Cellular diversity of the regenerating caudal fin – Science Advances | August 13th, 2020

Some skin, eggs and tissue samples are all that remain of Malaysia's last rhino, Iman, who died last November after years of failed breeding attempts.

Now scientists are pinning their hopes on experimental stem cell technology to bring back the Malaysian variant of the Sumatran rhinoceros, making use of cells from Iman and two other dead rhinos.

"I'm very confident," molecular biologist Muhammad Lokman Md Isa told Reuters in his laboratory at the International Islamic University of Malaysia.

"If everything is functioning, works well and everybody supports us, it's not impossible."

The smallest among the world's rhinos, the Sumatran species was declared extinct in the wild in Malaysia in 2015. Once it had roamed across Asia, but hunting and forest clearance reduced its numbers to just 80 in neighboringIndonesia.

Iman, 25, died in a nature reserve on Borneo island, following massive blood loss caused by uterine tumors, within six months of the death of Malaysia's last male rhino, Tam.

Efforts to get the two to breed had not worked.

"He was the equivalent of a 70-year-old man, so of course you don't expect the sperm to be all that good," said John Payne of the Borneo Rhino Alliance (BORA), who has campaigned for about four decades to save Malaysia's rhinos.

"It was obvious that, to increase the chances of success, one should get sperm and eggs from the rhinos inIndonesia. But right till today,Indonesiais still not keen on this."

Across the border

Indonesia's environment ministry disputed accusations of cross-border rivalry as a reason why Malaysia's rhinos died out, saying talks continue on ways to work with conservationists in the neighboring southeast Asian nation.

"Because this is part of diplomatic relations, the implementation must be in accordance with the regulation of each country," said Indra Exploitasia, the ministry's director for biodiversity conservation.

The Malaysian scientists plan to use cells from the dead rhinos to produce sperm and eggs that will yield test-tube babies to be implanted into a living animal or a closely related species, such as the horse.

The plan is similar to one for the African northern white rhinoceros, which number just two. Researchers in that effort reported some success in 2018 in producing embryonic stem cells for the southern white rhino.

But the process is still far from producing a whole new animal, say Thomas Hildebrandt and Cesare Galli, the scientists leading the research.

And even if it worked, the animals' lack of genetic diversity could pose a threat to long-term survival, Galli told Reuters.

Indonesian scientist Arief Boediono is among those helping in Malaysia, hoping success will provide lessons to help his country's rhinos.

"It may take five, 10, 20 years, I don't know," Arief added. "But there has already been some success involving lab rats in Japan, so that means there is a chance."

Japanese researchers have grown teeth and organs such as pancreas and kidneys using embryonic stem cells from rats and mice in efforts to grow replacement human organs.

For now, however, Iman's hide will be stuffed and put on display alongside Tam in a Borneo museum.

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Back from the dead? Stem cells give hope for revival of Malaysia's extinct rhinos - The Jakarta Post - Jakarta Post

Skin Stem Cells Comments Off on Back from the dead? Stem cells give hope for revival of Malaysia’s extinct rhinos – The Jakarta Post – Jakarta Post | August 13th, 2020

Aug 13 (Reuters) - Every week, Reuters journalists produce scores of multimedia features and human-interest stories from around the world.

Below are some engaging stories selected by our editors, as well as explanatory context and background on world headlines. For a full schedule of news and events, please go to our editorial calendar on Reuters Connect here

Baby George, born amid Beirut blast, is light in the darkness

BEIRUT, Aug 12 - Stepping into the delivery room where his wife Emmanuelle was about to give birth, Edmond Khnaisser meant to capture their sons first moments on camera. Instead, he recorded the instant the biggest blast in Lebanons history sent windows crashing onto the hospital bed. (LEBANON-SECURITY/BLAST-BABY (TV, PIX), moved, 401 words)

Squeegee selfies: Tel Aviv tower-washer is rising TikTok star

TEL AVIV, Aug 11 - Twirling to hip hop over chasms of steel and glass, soapy squeegee in one hand and a smartphone in the other, Noa Toledo is an Israeli social media star who aims to encourage other women to take on her traditionally male-dominated job. (ISRAEL-SOCIALMEDIA/WINDOW WASHER (TV, PIX), moved, 155 words)

From carats to peanuts: how a pandemic upended the global diamond industry

JOHANNESBURG/MUMBAI, Aug 12 - As the coronavirus pandemic shuttered mines from Lesotho to Canada and disrupted supply chains, Rajen Patel swapped diamond polishing for peanut farming. (HEALTH-CORONAVIRUS/DIAMONDS (PIX, GRAPHICS), by Helen Reid, Tanisha Heiberg and Rajendra Jadhav, 828 words)

Raphael did a nose-job in self-portrait, face reconstruction suggests

ROME, Aug 11 - Raphael probably didnt like his nose, and replaced it with an idealised version in his famous self-portrait. (ARTS-ITALY/RAPHAEL (PIX, TV), by Philip Pullella, 399 words)

Back from the dead? Stem cells give hope for revival of Malaysias extinct rhinos

KUANTAN, Malaysia, Aug 12 - Some skin, eggs and tissue samples are all that remain of Malaysias last rhino, Iman, who died last November after years of failed breeding attempts. (MALAYSIA-WILDLIFE/RHINO (TV, PIX), by Joseph Sipalan, 517 words)

Dream destination cafes offer taste of paradise in blockaded Gaza strip

GAZA, Aug 11 - Mediterranean waves crash below patrons snacking on freshly-caught fish at the Maldive Gaza cafe, offering a glimpse of paradise to Palestinians confined to the blockaded strip. (PALESTINIANS-GAZA/MALDIVES (TV, PIX), by Nidal al-Mughrabi, 207 words)

Virtually identical: Grounded Japanese try foreign holidays with a difference

TOKYO, Aug 12 - Japanese businessman Katsuo Inoue chose Italy for this years summer vacation, and he enjoyed the trimmings of a business class cabin and soaked up the sights of Florence and Rome - without ever leaving Tokyo. (HEALTH CORONAVIRUS/JAPAN-VR TRAVEL (TV, PIX), by Akira Tomoshige, 296 words)

For the art collector with everything, the $1.5 million COVID mask

MOTZA, Israel, Aug 12 - Art rather than ostentation is the rationale behind the worlds most expensive coronavirus mask, say the Israeli jewellers who are crafting the $1.5 million object for an unnamed U.S.-based client. (HEALTH-CORONAVIRUS/ISRAEL-MASK (TV, PIX), moved, 234 words)

Coping with campus coronavirus: U.S. fraternities, sororities give it the old college try

MADISON, Wisconsin, Aug 12 - Sixteen gallons of hand sanitizer sat in the foyer of the Alpha Epsilon Phi sorority house at the University of Wisconsin as house mother Karen Mullis reconfigured tables in the dining room to maintain social distancing. (HEALTH-CORONAVIRUS/FRATERNITIES-SORORITIES (PIX, GRAPHIC), by Brendan OBrien, 754 words)

Some U.S. colleges stick to in-person reopening in pandemic despite doubts, pushback

Aug 11 - Many U.S. universities are revamping campuses to resume in-person classes despite COVID-19, drawing criticism from some college town residents and critics who say schools are putting profits before public safety. (HEALTH-CORONAVIRUS/UNIVERSITIES (PIX, TV, GRAPHIC), by Jan Wolfe and Catherine Koppel, 729 words)

EXPLAINER-The U.S. push to extend U.N. arms embargo on Iran

Where Biden and Trump stand on key issues (tmsnrt.rs/3iDd4YG)

FACTBOX-Who is speaking at the Democratic National Convention - and why

NEWSMAKER-How Kamala Harris found the political identity that had eluded her

FACTBOX-Political crisis unfolds in Belarus after presidential vote

EXPLAINER-Microsofts TikTok bid spotlights Windows makers history with China

FACTBOX-Who is Jimmy Lai, the media tycoon arrested in Hong Kong?

FACTBOX-How financial firms in Hong Kong may be affected by U.S. sanctions

UNDERSTANDING COVID-19

EXPLAINER-When will a coronavirus vaccine be ready?

FACTBOX-World reaction to Russias COVID-19 vaccine

FACTBOX-U.S., UK spend billions to take lead in securing coronavirus vaccines

GRAPHIC-U.S. COVID-19 deaths drop for first time in four weeks (tmsnrt.rs/2WTOZDR)

The Lifeline Pipeline: the drugs, tests and tactics that may conquer coronavirus (reut.rs/3bhMUaE)

Coronavirus and the global economy (tmsnrt.rs/3cg7OXF)

The new normal: How far is far enough? (tmsnrt.rs/3dKqnnn)

Prominent people diagnosed with COVID-19

Global tracker (tmsnrt.rs/2W82n73)

U.S. tracker (tmsnrt.rs/2ySIhG0) (Compiled by Leela de Kretser, Patrick Enright and Tiffany Wu)

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IN CASE YOU MISSED ITSchedule of Reuters features from this week - Reuters

Skin Stem Cells Comments Off on IN CASE YOU MISSED ITSchedule of Reuters features from this week – Reuters | August 13th, 2020

Is it acne, a rash or maybe something more serious? Skin disorders can vary in both symptoms and severity. Some skin conditions are minor, some are serious but treatable, and others, like skin cancer, can be life-threatening. Here are 18 common (and a few less common) skin conditions with photos to help you ID them. Remember to always reach out to your physician for a proper diagnosis and treatment.

Acne | Actinic keratosis | Basal cell carcinoma | Blisters | Carbuncle | Cellulitis | Chicken pox | Cold sores | Contact dermatitis | Eczema | Hives | Latex allergy | Lupus | Measles | Melanoma | Psoriasis | Rosacea | Squamous cell carcinoma

Suffering from acne? Youre not alone. Acne is the most common condition dermatologists treat 40 to 50 million Americans struggle with acne at any given time.

Acne can show up almost anywhere on the skin as blackheads, papules and pustules or pimples, cysts and nodules

Acne starts when dead skin cells dont shed properly and clog your pores.

Some acne can be treated with over-the-counter products, while others require professional help, including prescription medication and treatments.

Read more about acne and how to treat it.

These precancerous lesions often appear as rough spots on the skin. Actinic keratosis is common, but if left untreated it can turn into squamous cell carcinoma.

The appearance of actinic keratosis can vary from bumps that look like pimples or acne to rough lesions that are red, pink or gray.

When cells in the skin called keratinocytes are damaged by UV rays, it can cause actinic keratosis.

While not always necessary, treatments may include removal of the actinic keratosis with liquid nitrogen, chemical peels, scraping or other therapies.

Read more about actinic keratosis and how to treat it.

Basal cell carcinoma is the most common type of skin cancer. It affects approximately 2.6 million people in the U.S. each year. Do you know how to spot it?

Basal cell carcinoma is much more common in people who have light skin. Symptoms tend to be the same color as the skin or pink. Its important to look for any changes in your skin.

Exposure from ultraviolet rays (UV) from the sun or indoor tanning is a primary cause of basal cell carcinoma.

Your dermatologist may be able to remove a basal cell carcinoma tumor when doing a biopsy. Sometimes a Mohs surgery is recommended.

Read more about basal cell carcinoma and how to spot it.

A common skin condition, most people develop blisters once in a while.

Blisters are small, painful sacs of fluid.

Blisters can be caused by friction, such as by a shoe rubbing against the skin, or by sunburns, heat or skin diseases.

Blisters tend to heal on their own, but a blister can be drained if its too painful.

Read more about blisters and how to treat them.

Sometimes confused with a spider bite, a carbuncle is a group of boils that stem from an infection of the skin and are connected to each other.

Red, tender bumps, or boils, that contain pus are signs of a carbuncle. Carbuncles can eventually rupture, and pus will leak out of them.

A bacterial infection, such as Staphylococcus aureus, is often the cause of a carbuncle.

If a carbuncle is small, you may be able to treat it at home with warm compresses and bandages. Otherwise, your dermatologist can make an incision to drain the pus.

Read more about carbuncles and how to treat them.

Cellulitis is an infection of the skin in which the skin becomes red and swollen. It typically occurs after you get a cut or wound.

When you have cellulitis, an area of your skin often on one of your legs becomes red, swollen, warm and possibly painful.

Cellulitis can be caused by two different types of bacteria: streptococcus (aka strep) or staphylococcus (aka staph).

Antibiotics like penicillin, cephalosporin or erythromycin are normally used to treat cellulitis.

Read more about cellulitis and how to treat it.

Also called varicella, this highly contagious disease mostly strikes children.

A fever may precede it, but the unique chicken pox rash appears on the skin with itchy blisters that look like lots of little dew drops.

The varicella-zoster virus (VZV) causes chicken pox as well as shingles. Its unlikely to get chicken pox if youve had the chicken pox vaccine.

The best treatment for chicken pox is prevention through vaccination. An early case of chicken pox may be treated with antiviral drugs. Other remedies can be used to ease symptoms.

Read more about chicken pox and how to treat it.

Trending stories,celebrity news and all the best of TODAY.

Also known as fever blisters, cold sores are blisters, or clusters of blisters, that appear on your lips or near your mouth.

Symptoms of cold sores can vary. The sores may start with a tingling, burning or other sensation, then break open and scab over.

Cold sores are caused by the herpes simplex virus. Outbreaks are triggered by stress, fatigue, illness and other factors.

Read more about cold sores and how to treat them.

Almost everyone gets contact dermatitis at some point. There are two main types of contact dermatitis allergic and irritant. Both trigger a rash.

Symptoms of allergic contact dermatitis may include itching, rash, dryness and other symptoms. Cracked, itchy, chapped skin with sores may be signs of irritant contact dermatitis.

Contact dermatitis is caused by something that touches your skin like poison ivy, nickel, fragrances, latex or other irritants and triggers a rash.

The best treatment for contact dermatitis is to avoid whatever it is that triggers your rash. Beyond that, your dermatologist may also recommend antihistamine pills, moisturizers or topical steroids.

Read more about contact dermatitis and how to treat it.

Eczema is a condition that causes red, itchy patches on the skin. It often starts at a young age often people with eczema get it when they're babies.

Eczema is almost always itchy, but otherwise symptoms can vary from person to person. Skin infected with eczema can be dry, dark, scaly, swollen or oozing.

Eczema may be caused by an overactive immune system, but its not entirely clear what causes the condition.

There is no cure for eczema, but symptoms can be managed with medications and other therapies.

Read more about eczema and how to treat it

The onset of hives can be mysterious, and though hives usually go away in less than 24 hours, new ones can repeatedly appear.

Hives appear on the skin as slightly swollen, raised pink or red patches. You may have one hive, a group of hives that may be separate or connected together.

Its difficult to pinpoint the cause of hives, but there are many triggers that can cause hives, from insect bites and allergic reactions to medication, stress and heat.

The go-to treatment for hives is usually antihistamines.

Read more about hives and how to treat them.

People with an allergy to latex are allergic to a protein found in the sap of the Brazilian rubber tree.

Different symptoms appear with different types of latex allergies. One type causes a rash on the skin; another can cause anaphylaxis, which can result in a swelling of the airways and difficulty breathing.

When your immune system reacts as though latex is a harmful substance, it causes an allergic reaction to latex.

Since theres no cure for latex allergies, your best bet is to avoid coming into contact with latex.

Read more about latex allergy and how to treat it.

An autoimmune disease that causes pain and inflammation, lupus can affect your skin, as well as your kidneys, heart, joints and lungs.

A red butterfly-shaped rash that appears on the nose and cheeks is one common sign of lupus, but symptoms of lupus will vary, depending on the type of lupus you have.

There are a number of factors that may play a role in whether you develop rosacea, but experts dont know for certain what causes the skin condition.

There is no cure for rosacea, but the condition can be managed to help keep symptoms from worsening.

Read more about lupus and how to treat it.

Also known as rubeola, measles is a contagious and potentially deadly disease that usually strikes children.

Beyond the signifying red, spotted rash, measles may also be accompanied by a fever, cough, runny nose and other symptoms.

A virus that infects the respiratory tract and spreads throughout the body causes measles. Its one of the most contagious diseases.

The best treatment is prevention through a vaccine. Otherwise, high doses of vitamin A, bed rest and medications to reduce pain and fever may help.

Read more about measles and how to treat it.

Its one of the less common skin cancers, but melanoma is the most dangerous because it can easily spread to other parts of your body.

Melanoma tumors tend to be black or brown, but can sometimes be pink, tan or white. Anyone can get melanoma, but people with light skin are at greater risk.

UV light exposure from ultraviolet rays from the sun or indoor tanning causes most melanomas.

Treatments depend on how advanced the melanoma is and where the tumor is located. It may include surgery, radiation, chemotherapy or other therapies.

Read more about melanoma and how to treat it.

Psoriasis affects more than 8 million people in the U.S. It typically starts in the teen years or early 20s, though it can occur at any age.

When you have psoriasis, your body makes new skin cells quickly, and the cells typically build up in thick, scaly patches on the skin called plaques.

There are a number of factors that may contribute to causing psoriasis. The immune system and genetics may play a role. Certain triggers can also cause the onset of psoriasis and psoriasis flare-ups.

Psoriasis doesnt have a cure, there are medications and treatments that can help manage the condition.

Read more about psoriasis and how to treat it.

This common inflammatory skin condition causes redness of the face.

In addition to causing facial redness, if rosacea is not treated, it can cause visible blood vessels, breakouts like acne and other symptoms.

There are a number of factors that may play a role in whether you develop rosacea, but experts dont know for certain what causes the skin condition.

There is no cure for rosacea, but the condition can be managed to help keep symptoms from worsening.

Read more about rosacea and how to treat it.

Also known as cutaneous squamous cell carcinoma, this cancer develops when the squamous cells in the top layer of your skin grow out of control.

Though its linked with exposure to ultraviolet rays, squamous cell carcinoma can crop up in areas that dont get much sun. Watch out for rough, scaly patches, sores that dont heal or anything else that looks suspicious.

Squamous cell carcinoma is mainly caused by UV rays from the sun or indoor tanning.

Treatments for squamous cell carcinoma may include surgery, radiation or other therapies. Catching it early is key.

Read more about squamous cell carcinoma and how to treat it.

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Skin Disorders: Pictures, symptoms, causes and help - TODAY - TODAY

Skin Stem Cells Comments Off on Skin Disorders: Pictures, symptoms, causes and help – TODAY – TODAY | August 13th, 2020

After months of reviewing close to 300 beauty products and wellness facilities, and tallying, here are the best skincare products of this year, and lest we forget, your top pick! And so without further ado, here are the Beauty & Wellness Awards winners.

As technology continues to advance and discoveries are made each day,we do our part in dipping our toe in the proverbial pool of beauty toexplore the latest and greatest. Embracing the new is part of our job asinvestigative beauty aficionados, and as we dig through the recentdebuts, weve found some newbies that have found a permanent spot onour top shelf that we highly recommend checking out.

1

Best Face Cream: First Aid Beauty Ultra Repair Cream

For even the most sensitive skin, FAB delivers animpressive amount of hydration without anyirritation. The luscious whipped-cream texturespreads easily over the face, yet still holds wellenough for make-up to sit over nicely.

Ultra Repair Cream

HK$249/170g; HK$109/56.7G

2

Best Hydrating Serum: Skin Need 100% Hyaluronic Acid B5

The ultimate water magnet, thisserum locks in all the hydration youneed. Its easily absorbed, so yourskin feels fresh and clean without atrace of stickiness. The heavy doseof hyaluronic acid binds and trapsmoisture to the skin.

100% Hyaluronic Acid B5

HK$598

3

Best Reparative Formula: Wildsmith Skin Active Repair Radiance Polisher

Exfoliate to your hearts content and skinsneed the gentle grains of walnut shell androsehip-seed powder sloughs away deadskin cells and polishes the skins surface. Mixthe desired amount with any facial cleanserto create your very own scrub.

Skin Active Repair Radiance Polisher

HK$254

4

Best Body Cream: Augustinus Bader The Body Cream

A fresh launch from world-leadingstem cell and biomedical pioneerand scientist, Professor AugustinusBader, The Body Cream is officiallythe newest must-have item in bodyand skin care. Powered by thebrands patented Trigger FactorComplex (TFC8), this cellularrenewal cream reawakens dormantstem cells and results in firmer,toned skin with a reduction incellulite and stretch marks.

5

Readers Choice: Drunk Elephant F-balm

Electrolytes pump us full of hydration. And if its good to ingest. Why wouldnt it be topically? This waterfacial masque hydratant nourishes and repairs parched skin while you sleep. Its cooling effects are especially appreciated this season.

All of the Drunk Elephant products are naturally formulated and cater directly to your skins health. Oi Tak Kan, Prestige Reader

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Beauty & Wellness Awards 2020: New Kids on the Block - Prestige Online

Skin Stem Cells Comments Off on Beauty & Wellness Awards 2020: New Kids on the Block – Prestige Online | August 12th, 2020

KUANTAN, Malaysia Some skin, eggs and tissue samples are all that remain of Malaysia's last rhino, Iman, who died last November after years of failed breeding attempts.

Now scientists are pinning their hopes on experimental stem cell technology to bring back the Malaysian variant of the Sumatran rhinoceros, making use of cells from Iman and two other dead rhinos.

"I'm very confident," molecular biologist Muhammad Lokman Md Isa told Reuters in his laboratory at the International Islamic University of Malaysia.

"If everything is functioning, works well and everybody supports us, it's not impossible."

The smallest among the world's rhinos, the Sumatran species was declared extinct in the wild in Malaysia in 2015. Once it had roamed across Asia, but hunting and forest clearance reduced its numbers to just 80 in neighbouring Indonesia.

Iman, 25, died in a nature reserve on Borneo island, following massive blood loss caused by uterine tumours, within six months of the death of Malaysia's last male rhino, Tam.

Efforts to get the two to breed had not worked.

"He was the equivalent of a 70-year-old man, so of course you don't expect the sperm to be all that good," said John Payne of the Borneo Rhino Alliance (BORA), who has campaigned for about four decades to save Malaysia's rhinos.

"It was obvious that, to increase the chances of success, one should get sperm and eggs from the rhinos in Indonesia. But right till today, Indonesia is still not keen on this."

ACROSS THE BORDER

Indonesia's environment ministry disputed accusations of cross-border rivalry as a reason why Malaysia's rhinos died out, saying talks continue on ways to work with conservationists in the neighbouring southeast Asian nation.

"Because this is part of diplomatic relations, the implementation must be in accordance with the regulation of each country," said Indra Exploitasia, the ministry's director for biodiversity conservation.

The Malaysian scientists plan to use cells from the dead rhinos to produce sperm and eggs that will yield test-tube babies to be implanted into a living animal or a closely related species, such as the horse.

The plan is similar to one for the African northern white rhinoceros, which number just two. Researchers in that effort reported some success in 2018 in producing embyronic stem cells for the southern white rhino.

But the process is still far from producing a whole new animal, say Thomas Hildebrandt and Cesare Galli, the scientists leading the research.

And even if it worked, the animals' lack of genetic diversity could pose a threat to long-term survival, Galli told Reuters.

Indonesian scientist Arief Boediono is among those helping in Malaysia, hoping success will provide lessons to help his country's rhinos.

"It may take five, 10, 20 years, I don't know," Arief added. "But there has already been some success involving lab rats in Japan, so that means there is a chance."

Japanese researchers have grown teeth and organs such as pancreas and kidneys using embryonic stem cells from rats and mice in efforts to grow replacement human organs.

For now, however, Iman's hide will be stuffed and put on display alongside Tam in a Borneo museum.

(Editing by Matthew Tostevin and Clarence Fernandez)

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Back From the Dead? Stem Cells Give Hope for Revival of Malaysia's Extinct Rhinos - The New York Times

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Skin Stem Cells Comments Off on Going On At The Greenville Library – WSPA 7News | August 12th, 2020

In mouse studies, the specialized grafts integrated with host networks and behaved much like neurons in a healthy, undamaged spinal cord.

Using stem cells to restore lost functions due to spinal cord injury (SCI) has long been an ambition of scientists and doctors. Nearly 18,000 people in the United States suffer SCIs each year, with another 294,000 persons living with an SCI, usually involving some degree of permanent paralysis or diminished physical function, such as bladder control or difficulty breathing.

In a new study, published August 5, 2020 in Cell Stem Cell , researchers at University of California San Diego School of Medicine report successfully implanting highly specialized grafts of neural stem cells directly into spinal cord injuries in mice, then documenting how the grafts grew and filled the injury sites, integrating with and mimicking the animals existing neuronal network.

Until this study, said the studys first author Steven Ceto, a postdoctoral fellow in the lab of Mark H. Tuszynski, MD, PhD, professor of neurosciences and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, neural stem cell grafts being developed in the lab were sort of a black box.

Although previous research, including published workby Tuszynski and colleagues, had shown improved functioning in SCI animal models after neural stem cell grafts, scientists did not know exactly what was happening.

We knew that damaged host axons grew extensively into (injury sites), and that graft neurons in turn extended large numbers of axons into the spinal cord, but we had no idea what kind of activity was actually occurring inside the graft itself, said Ceto. We didnt know if host and graft axons were actually making functional connections, or if they just looked like they could be.

Ceto, Tuszynski and colleagues took advantage of recent technological advances that allow researchers to both stimulate and record the activity of genetically and anatomically defined neuron populations with light rather than electricity. This ensured they knew exactly which host and graft neurons were in play, without having to worry about electric currents spreading through tissue and giving potentially misleading results.

They discovered that even in the absence of a specific stimulus, graft neurons fired spontaneously in distinct clusters of neurons with highly correlated activity, much like in the neural networks of the normal spinal cord. When researchers stimulated regenerating axons coming from the animals brain, they found that some of the same spontaneously active clusters of graft neurons responded robustly, indicating that these networks receive functional synaptic connections from inputs that typically drive movement. Sensory stimuli, such as a light touch and pinch, also activated graft neurons.

We showed that we could turn on spinal cord neurons below the injury site by stimulating graft axons extending into these areas, said Ceto. Putting all these results together, it turns out that neural stem cell grafts have a remarkable ability to self-assemble into spinal cord-like neural networks that functionally integrate with the host nervous system. After years of speculation and inference, we showed directly that each of the building blocks of a neuronal relay across spinal cord injury are in fact functional.

Tuszynski said his team is now working on several avenues to enhance the functional connectivity of stem cell grafts, such as organizing the topology of grafts to mimic that of the normal spinal cord with scaffolds and using electrical stimulation to strengthen the synapses between host and graft neurons.

While the perfect combination of stem cells, stimulation, rehabilitation and other interventions may be years off, patients are living with spinal cord injury right now, Tuszynski said. Therefore, we are currently working with regulatory authorities to move our stem cell graft approach into clinical trials as soon as possible. If everything goes well, we could have a therapy within the decade.

Co-authors of the study are Kohel J. Sekiguchi and Axel Nimmerjahn, Salk Institute for Biological Studies and Yoshio Takashima, UC San Diego and Veterans Administration Medical Center, San Diego.

Funding for this research came, in part, from Wings for Life, the University of California Frontiers of Innovation Scholars Program, the Veterans Administration (Gordon Mansfield Spinal Cord Injury Collaborative Consortium, RR&D B7332R), the National Institutes of Health (grants NS104442 and NS108034), The Craig H. Neilsen Foundation, the Kakajima Foundation, the Bernard and Anne Spitzer Charitable Trust and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

Source: Scott LaFee, UC San Diego School of Medicine

Posted on August 5th, 2020 in Uncategorized.

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Stem Cell Grafts Show Functionality in Spinal Cord Injuries

Spinal Cord Stem Cells Comments Off on Stem Cell Grafts Show Functionality in Spinal Cord Injuries | August 12th, 2020

Colorized scanning electron micrograph of a cultured human neuron. Photo credit: Thomas Deerinck, UC San Diego National Center for Microscopy and Imaging

Using stem cells to restore lost functions due to spinal cord injury (SCI) has long been an ambition of scientists and doctors. Nearly 18,000 people in the United States suffer SCIs each year, with another 294,000 persons living with an SCI, usually involving some degree of permanent paralysis or diminished physical function, such as bladder control or difficulty breathing.

In a new study, published August 5, 2020 in Cell Stem Cell, researchers at University of California San Diego School of Medicine report successfully implanting highly specialized grafts of neural stem cells directly into spinal cord injuries in mice, then documenting how the grafts grew and filled the injury sites, integrating with and mimicking the animals existing neuronal network.

Until this study, said the studys first author Steven Ceto, a postdoctoral fellow in the lab of Mark H. Tuszynski, MD, PhD, professor of neurosciences and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, neural stem cell grafts being developed in the lab were sort of a black box.

Although previous research, including published work by Tuszynski and colleagues, had shown improved functioning in SCI animal models after neural stem cell grafts, scientists did not know exactly what was happening.

We knew that damaged host axons grew extensively into (injury sites), and that graft neurons in turn extended large numbers of axons into the spinal cord, but we had no idea what kind of activity was actually occurring inside the graft itself, said Ceto. We didnt know if host and graft axons were actually making functional connections, or if they just looked like they could be.

Ceto, Tuszynski and colleagues took advantage of recent technological advances that allow researchers to both stimulate and record the activity of genetically and anatomically defined neuron populations with light rather than electricity. This ensured they knew exactly which host and graft neurons were in play, without having to worry about electric currents spreading through tissue and giving potentially misleading results.

They discovered that even in the absence of a specific stimulus, graft neurons fired spontaneously in distinct clusters of neurons with highly correlated activity, much like in the neural networks of the normal spinal cord. When researchers stimulated regenerating axons coming from the animals brain, they found that some of the same spontaneously active clusters of graft neurons responded robustly, indicating that these networks receive functional synaptic connections from inputs that typically drive movement. Sensory stimuli, such as a light touch and pinch, also activated graft neurons.

We showed that we could turn on spinal cord neurons below the injury site by stimulating graft axons extending into these areas, said Ceto. Putting all these results together, it turns out that neural stem cell grafts have a remarkable ability to self-assemble into spinal cord-like neural networks that functionally integrate with the host nervous system. After years of speculation and inference, we showed directly that each of the building blocks of a neuronal relay across spinal cord injury are in fact functional.

Tuszynski said his team is now working on several avenues to enhance the functional connectivity of stem cell grafts, such as organizing the topology of grafts to mimic that of the normal spinal cord with scaffolds and using electrical stimulation to strengthen the synapses between host and graft neurons.

While the perfect combination of stem cells, stimulation, rehabilitation and other interventions may be years off, patients are living with spinal cord injury right now, Tuszynski said. Therefore, we are currently working with regulatory authorities to move our stem cell graft approach into clinical trials as soon as possible. If everything goes well, we could have a therapy within the decade.

Co-authors of the study are Kohel J. Sekiguchi and Axel Nimmerjahn, Salk Institute for Biological Studies and Yoshio Takashima, UC San Diego and Veterans Administration Medical Center, San Diego.

Funding for this research came, in part, from Wings for Life, the University of California Frontiers of Innovation Scholars Program, the Veterans Administration (Gordon Mansfield Spinal Cord Injury Collaborative Consortium, RR&D B7332R), the National Institutes of Health (grants NS104442 and NS108034), The Craig H. Neilsen Foundation, the Kakajima Foundation, the Bernard and Anne Spitzer Charitable Trust and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

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Implanted Neural Stem Cell Grafts Show Functionality in ...

Spinal Cord Stem Cells Comments Off on Implanted Neural Stem Cell Grafts Show Functionality in … | August 12th, 2020

Although spinal cord injuries (SCI) are not as prevalent as other debilitating conditions, they can be particularly devastating. Patients often lose motor control and sensibility and require assistance with everyday tasks. Most people are familiar with the case of Christopher Reeve, an American actor who played Superman in the 70s and 80s. He suffered a cervical spinal cord injury and was left paralyzed from the neck down. Reeve became an advocate for research into a potential cure using stem cells.

The World Health Organization estimates that every year up to 500,000 people suffer this type of injury worldwide. In Canada, approximately 85,000 people are currently living with some type of SCI.

The possibility of repairing damage sustained by the spinal cord is one of the most exciting potential applications of regenerative medicine. There have been promising advancements in this field and it is just a matter of time before they give way to actual treatments. Access to these treatments is just one of the many advantages of cell banking.

Inside the spinal column, which runs from the base of the skull to the coccyx, lies a fragile structure made up of nervous tissue. This is the spinal cord. Its job is to carry nerve signals from the brain to the rest of the body.

The spinal cord is very delicate and while it is protected by the vertebrae, it can easily be damaged either by trauma or disease. Injuries are graded according to their severity on a scale designed by the American Spinal Injury Association (ASIA) that goes from A to E (A being a complete injury, where all motor and sensory function is lost. E represents normal function). The severity of the injury is inversely correlated with the probability of recovery. According to the American Association of Neurological Surgeons, nearly half of all spinal cord injuries are complete.

In addition to the physical damage, spinal cord injuries are incredibly challenging in psychological terms. The more severe the injury, the more likely it is that the individual will lose the ability to care for himself. As reported in Mayo Clinic Proceedings, adults with spinal cord injury are at a higher risk of developing mental health disorders. Additionally, the rate of suicide increases three-fold among patients with this type of injury compared to the general population.

In a study published in Topics in Spinal Cord Injury Rehabilitation, researchers from the University of Alabama analyzed data from patients that sustained spinal cord injuries from 2005 to 2011. They found that automobile crashes (31.5% of cases) and falls (25.3%) account for more than half of all incidents. Other common causes are gunshot wounds, motorcycle crashes, and diving accidents. Although not frequent, diseases can cause spinal cord injury as well, specifically cancer, and osteoporosis.

Considering all causes, men account for 8 out of every 10 cases of spinal cord injury. Additionally, according to the Mayo Clinic, people are more likely to suffer traumatic cord injuries between the ages of 16 and 30. Avoiding risky behavior is the most effective strategy for preventing spinal cord injury.

In addition to the ASIA scale, which ranks injury by the severity of the damage, spinal cord injuries can be classified depending on the area affected. There are four types of spinal cord injury: cervical, thoracic, lumbar, and sacral.

The uppermost portion of the spine (vertebrae C1 to C7) is called the cervical section. Traumatic cord injuries in this area can lead to quadriplegia or full paralysis. This is the sort of injury that actor Christopher Reeve sustained. He shattered his C-1 and C-2 vertebrae in a horseback riding accident. Baseball player Roy Campanella damaged his C-5 and C-6 vertebrae in an automobile accident.

The thoracic spine is comprised of 12 vertebrae (T-1 to T-12) and it is located below the cervical section. An injury to this area could result in loss of use of the chest, upper back, and abdominals.

The lumbar section of the spine is located in the lower back. It comprises five vertebrae (L1 to L5). An injury to this area can leave an individual paraplegic, unable to move or feel anything below the point of injury. Deng Pufang, son of Chinas former leader Deng Xiaoping, suffered a lumbar spinal cord injury and became paralyzed.

The sacral section is located between the lumbar section and the coccyx. Injury to this area may cause loss of function in the hips and legs. Bladder function may be compromised as well. Injuries to this section of the spine are less common than cervical, thoracic, or lumbar injuries.

A discovery made by researchers John B. Gurdon and Shinya Yamanaka, for which they won the 2012 Nobel Prize in Medicine, may hold the key to repairing spinal cord injury. They found a way to induce adult cells, like those located in your hair follicles, to become pluripotent. Once this happens, these cells, called induced pluripotent stem cells (iPSCs), can become any cell type in the body.

A team of researchers from Keio University in Japan injected mice that had suffered spinal cord injury with neural cells derived from human iPSCs. These cells were able to successfully migrate and differentiate into their appropriate neural lineages, and they performed synapses. This means that they became exactly the type of cell needed in the place of injury and they successfully communicated with each other.

According to the scientists, compared to the control group, the mice injected with iPSCs had a significantly better functional recovery. The results of this trial, published in Proceedings of the National Academy of Sciences of the United States of America, are a step forward in the path towards eventually promoting complete functional recovery of spinal cord injury in humans.

Once this method is perfected and made available to the public, doctors will need a cell sample that they can turn into neural cells to treat people who suffer from spinal cord injury. It is important to note that the sooner that sample is taken and preserved, the higher its therapeutic potential will be, not only to treat spinal cord injury but many other conditions like Parkinsons, Alzheimers and macular degeneration.This means that the sooner you take action and have your live cells cryopreserved, the better prepared you will be to take advantage of the revolution of regenerative medicine that is coming. To learn more about the ways you can have your cells banked at Acorn, click here.

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Repairing damage caused by spinal cord injury with stem cells

Spinal Cord Stem Cells Comments Off on Repairing damage caused by spinal cord injury with stem cells | August 12th, 2020

According to latest research report on Global Stem Cell Banking Market report provides information related to market size, production, CAGR, gross margin, growth rate, emerging trends, price, and other important factors. Focusing on the key momentum and restraining factors in this market, the report also provides a complete study of future trends and developments in the market.

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In terms of geography, this research report covers almost all major regions around the world such as North America, Europe, South America, Middle East, Africa, and the Asia Pacific. Europe and North America are expected to increase over the next few years. Stem Cell Banking markets in the Asia-Pacific region are expected to experience significant growth during the forecast period. Advanced technology and innovation are the most important characteristics of North America and the main reason why the United States dominates the world market. The Stem Cell Banking market in South America is also expected to expand in the near future.

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Stem Cell Banking Market Applications, Types and Future Outlook Report 2020-2025 - Express Journal

Bone Marrow Stem Cells Comments Off on Stem Cell Banking Market Applications, Types and Future Outlook Report 2020-2025 – Express Journal | August 12th, 2020

TEL AVIV, Israel, Aug. 12, 2020 /PRNewswire/ -- Cellect Biotechnology Ltd. (NASDAQ: APOP), a developer of innovative technology which enables the functional selection of stem cells, today reported financial and operating results for the second quarter ended June 30, 2020. The Company's six-month progress includes the development of several strategic initiatives, including growth-oriented opportunities in pain management and COVID-19 related therapeutics.

"Despite the COVID-19 pandemic business disruptions and the near-term delays to completing and commencing our clinical programs in Israel and the U.S., respectively, we acted swiftly over the past few months to leverage our sought-after technology to create several long-term business initiatives to enhance our value," commented Dr. Shai Yarkoni, Chief Executive Officer. "In addition to pursuing a potential merger with a global leader in the high growth medical-grade cannabis market, which is being delayed due to COVID-19, we have either initiated or are contemplating other business development activities that will greatly benefit from our innovation, technology and know-how. I believe each of these opportunities represents meaningful catalysts for Cellect in multi-billion-dollar markets, subject to resolution of the COVID-19 pandemic and return to normal course of business."

Notwithstanding the continued delays due to COVID-19, the Company remains focused on the following operational and clinical objectives:

The Company's cash and cash equivalents totaled $7 million as of June 30, 2020, which includes the approximately $1.5 million (gross before expenses)resulting from several investors exercising certain warrants that were issued in February 2019.

SecondQuarter 2020 Financial Results:

*For the convenience of the reader, the amounts above have been translated from NIS into U.S. dollars, at the representative rate of exchange on June 30, 2020 (U.S. $1 = NIS 3.466).

About Cellect Biotechnology Ltd.

Cellect Biotechnology (APOP) has developed a breakthrough technology, for the selection of stem cells from any given tissue, that aims to improve a variety of stem cell-based therapies.

The Company's technology is expected to provide researchers, clinical community and pharma companies with the tools to rapidly isolate stem cells in quantity and quality allowing stem cell-based treatments and procedures in a wide variety of applications in regenerative medicine. The Company's current clinical trial is aimed at bone marrow transplantations in cancer treatment.

Forward Looking Statements

This press release contains forward-looking statements about the Company's expectations, beliefs and intentions. Forward-looking statements can be identified by the use of forward-looking words such as "believe", "expect", "intend", "plan", "may", "should", "could", "might", "seek", "target", "will", "project", "forecast", "continue" or "anticipate" or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. For example, forward-looking statements are used in this press release when we discuss Cellect's expectations regarding timing of the commencement of its planned U.S. clinical trial and its plan to reduce operating costs. These forward-looking statements and their implications are based on the current expectations of the management of the Company only and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. In addition, historical results or conclusions from scientific research and clinical studies do not guarantee that future results would suggest similar conclusions or that historical results referred to herein would be interpreted similarly in light of additional research or otherwise. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: the Company's history of losses and needs for additional capital to fund its operations and its inability to obtain additional capital on acceptable terms, or at all; the Company's ability to continue as a going concern; uncertainties of cash flows and inability to meet working capital needs; the Company's ability to obtain regulatory approvals; the Company's ability to obtain favorable pre-clinical and clinical trial results; the Company's technology may not be validated and its methods may not be accepted by the scientific community; difficulties enrolling patients in the Company's clinical trials; the ability to timely source adequate supply of FasL; risks resulting from unforeseen side effects; the Company's ability to establish and maintain strategic partnerships and other corporate collaborations; the scope of protection the Company is able to establish and maintain for intellectual property rights and its ability to operate its business without infringing the intellectual property rights of others; competitive companies, technologies and the Company's industry; unforeseen scientific difficulties may develop with the Company's technology; the Company's ability to retain or attract key employees whose knowledge is essential to the development of its products; and the Company's ability to pursue any strategic transaction or that any transaction, if pursued, will be completed. Any forward-looking statement in this press release speaks only as of the date of this press release. The Company undertakes no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws. More detailed information about the risks and uncertainties affecting the Company is contained under the heading "Risk Factors" in Cellect Biotechnology Ltd.'s Annual Report on Form 20-F for the fiscal year ended December 31, 2019 filed with the U.S. Securities and Exchange Commission, or SEC, which is available on the SEC's website, http://www.sec.gov, and in the Company's periodic filings with the SEC.

Cellect Biotechnology Ltd.

Consolidated Statement of Operation

Convenience

translation

Six months

ended

Six months ended

Three months ended

June 30,

June 30,

June 30,

2020

2020

2019

2020

2019

Unaudited

Unaudited

U.S. dollars

NIS

(In thousands, except share and per

share data)

Research and development expenses

837

2,901

7,086

1,364

3,564

General and administrative expenses

1,356

4,703

5,064

2,116

2,709

Operating loss

2,193

7,604

12,150

3,480

6,273

Financial expenses (income) due to warrants exercisable into shares

1,098

3,807

(7,111)

4,697

(5,919)

Other financial expenses (income), net

(15)

(55)

880

627

462

Total comprehensive loss

3,276

11,356

5,919

8,804

816

Loss per share:

Basic and diluted loss per share

0.010

0.034

0.029

0.024

0.004

Weighted average number of shares outstanding used to compute basic and diluted loss per share

338,182,275

338,182,275

200,942,871

365,428,101

224,087,799

Cellect Biotechnology Ltd.

Consolidated Balance Sheet Data

Convenience

translation

June 30,

June 30,

December 31,

2020

2020

2019

Unaudited

Unaudited

Audited

U.S. dollars

NIS

(In thousands, except share and per

share data)

CURRENT ASSETS:

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Cellect Biotechnology Reports Second Quarter Financial and Operating Results; First Half 2020 Strategic Developments Create Long-Term Revenue...

Bone Marrow Stem Cells Comments Off on Cellect Biotechnology Reports Second Quarter Financial and Operating Results; First Half 2020 Strategic Developments Create Long-Term Revenue… | August 12th, 2020

DUBLIN, Aug. 11, 2020 /PRNewswire/ -- The "Global Induced Pluripotent Stem Cell (iPS Cell) Industry Report" report has been added to ResearchAndMarkets.com's offering.

Since the discovery of induced pluripotent stem cells (iPSCs) a large and thriving research product market has grown into existence, largely because the cells are non-controversial and can be generated directly from adult cells. It is clear that iPSCs represent a lucrative market segment because methods for commercializing this cell type are expanding every year and clinical studies investigating iPSCs are swelling in number.

Therapeutic applications of iPSCs have surged in recent years. 2013 was a landmark year in Japan because it saw the first cellular therapy involving the transplant of iPSCs into humans initiated at the RIKEN Center in Kobe, Japan. Led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB), it investigated the safety of iPSC-derived cell sheets in patients with macular degeneration. In another world-first, Cynata Therapeutics received approval in 2016 to launch the world's first formal clinical trial of an allogeneic iPSC-derived cell product (CYP-001) for the treatment of GvHD. Riding the momentum within the CAR-T field, Fate Therapeutics is developing FT819, its off-the-shelf iPSC-derived CAR-T cell product candidate. Numerous physician-led studies using iPSCs are also underway in Japan, a leading country for basic and applied iPSC applications.

iPS Cell Commercialization

Methods of commercializing induced pluripotent stem cells (iPSCs) are diverse and continue to expand. iPSC cell applications include, but are not limited to:

Since the discovery of iPSC technology in 2006, significant progress has been made in stem cell biology and regenerative medicine. New pathological mechanisms have been identified and explained, new drugs identified by iPSC screens are in the pipeline, and the first clinical trials employing human iPSC-derived cell types have been initiated. The main objectives of this report are to describe the current status of iPSC research, patents, funding events, industry partnerships, biomedical applications, technologies, and clinical trials for the development of iPSC-based therapeutics.

Key Topics Covered:

1. Report Overview

2. Introduction

3. History of Induced Pluripotent Stem Cells (IPSCS)

4. Research Publications on IPSCS

5. IPSCS: Patent Landscape

6. Clinical Trials Involving IPSCS

7. Funding for IPSC

8. Generation of Induced Pluripotent Stem Cells: An Overview

9. Human IPSC Banking

10. Biomedical Applications of IPSCS

11. Other Novel Applications of IPSCS

12. Deals in the IPSCS Sector

13. Market Overview

14. Company Profiles

For more information about this report visit https://www.researchandmarkets.com/r/kpc95y

About ResearchAndMarkets.comResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

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Opportunities in the Global Induced Pluripotent Stem Cell (iPS Cell) Industry - PRNewswire

IPS Cell Therapy Comments Off on Opportunities in the Global Induced Pluripotent Stem Cell (iPS Cell) Industry – PRNewswire | August 11th, 2020

The spinal cord is a bundle of nerves inside the spine that gives your body structure and support. Spinal cord injuries (SCIs) tend to be devastating and most are permanent. Recent research has shown that motor neuron obtained from skin cells could serve as potential treatments for spinal cord injuries, and thus has received considerable research attention. With this, a new door has been opened for treating not only spinal cord injuries, caused by workplace accidents and car crashes, but also Lou Gehrigs disease, known as amyotrophic lateral sclerosis or ALS.

A research team, led by Professor Jeong Beom Kim and his research team in the School of Life Sciences at UNIST has demonstrated that human fibroblasts can be converted into induced motor neurons (iMNs) by sequentially inducing two transcription factors, POU5F1(OCT4) and LHX3. The research team further investigated the therapeutic effects of iMNs for treating traumatic spinal cord injury using rodent spinal cord injury model. Their findings indicate that the sequential induction of two transcription factors is essential for generating self-renewing iMNICs more efficiently. This method not only ensures large-scale production of pure iMNs, but also facilitates the feasibility of iMNs for SCI treatment.

The spinal cord is responsible for transmitting signals from the brain to the rest of the body, and vice versa. Along with motor and sensory deficits, damage to the spinal cord can cause long-term complications, including limited mobility. Although there are many treatment options available for people with SCI, most of them have adverse side effects that impact therapy. And this is why stem cell (SC) therapies to restore functions of damaged tissues are attracting attention, recently. Among those cells constituting the spinal cord, motor neurons that involved in the regulation of muscle function have emerged as a promising candidate for the stem cell-based therapy for SCIs. Despite these encouraging advances, ethical issue of embryonic stem cells (ESCs) and tumorigenic potential of induced pluripotent stem cells (iPSCs) have impeded their translations into clinical trials.

Figure 1. The experimental scheme for the generation of induced motor neurons (iMNs) from human fibroblasts via sequential transduction of two transcription factors.

To overcome these limitations, Professor Kim and his research team established an advanced direct conversion strategy to generate iMNs from human fibroblasts in large-scale with high purity, thereby providing a cell source for the treatment of SCI. These iMNs possessed spinal cord motor neuronal identity and exhibit hallmarks of spinal MNs, such as neuromuscular junction formation capacity and electrophysiological properties in vitro. Importantly, their findings also show that transplantation of iMNs improved locomotor function in rodent SCI model without tumor formation. According to the research team, This proof-of-concept study shows that our functional iMNs can be employed to cell-based therapy as an autologous cell source. Through this, they resolved the problem of immune rejection, and thus reduce the risk of cancer.

In the study, we succeeded in generating iMNs from human fibroblasts by overexpressing POU5F1(OCT4) and LHX3, says Hyunah Lee (Combined MS/Ph.D program of Life Sciences, UNIST), the first author of the study.

Figure 2. Therapeutic effects of iMNs in rat spinal cord injury model in vivo. (A) The position of hindlimbs in control rat and iMN-transplanted rat after 8 weeks of transplantation. (B) C staining analysis of spinal cords after 8 weeks of transplantation (I; Control, J; iMN-transplanted).

The developed motor nerve cell manufacturing method has the advantage of being capable of mass production. A sufficient amount of cells is required for patient clinical treatment, but the existing direct differentiation technique has limited the number of cells that can be obtained. On the other hand, the method developed by the research team is capable of mass production because it undergoes an intermediate cell stage capable of self-renewal. After injecting the produced cells into the spinal cord injury mice, it was confirmed that the lost motor function is restored and the nerves are regenerated in the damaged spinal cord tissue.

Although further investigation on mechanism responsible for cell fate conversion may be needed, our strategy is a safer and simpler methodology that may provide new insights to develop personalized stem cell therapy and drug screening for MN diseases or spinal cord disorders, says Professor Kim. If combined with SuPine Patch, an adhesive hydrogel patches with the purpose of regenerating the damaged spinal cords, its therapeutic effects will be maximized. He adds, As the incidence of spinal cord injury is high due to industrial accidents, synergistic effects with public hospitals specializing in industrial accidents scheduled to be built in Ulsan should be expected.

This study has been jointly carried out with Professor Kims startup company, SuPine Therapeutics Inc. with the support of the Ministry of SMEs and Startups (MSS). The findings of this research have been published in the 2020 June issue of the online edition of eLife, a renowned academic journal of the European Molecular Biology Organizationl (EMBO).

Journal Reference

Hyunah Lee, Hye Yeong Lee, Byeong Eun Lee, et al., Sequentially induced motor neurons from human fibroblasts facilitate locomotor recovery in a rodent spinal cord injury model, eLife, (2020).

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New Study Presents Cell-based Therapy for MN Diseases or Spinal Cord Disorders - Mirage News

Spinal Cord Stem Cells Comments Off on New Study Presents Cell-based Therapy for MN Diseases or Spinal Cord Disorders – Mirage News | August 11th, 2020