Category Archives: Stem Cells

Discovery of RNA regulator could lead to a better understanding of diseases like cancer and influenza

Singapore, Sept 9, 2013 - (ACN Newswire) - Scientists at A*STAR's Genome Institute of Singapore (GIS), in collaboration with their counterparts from Canada, Hong Kong and US, have discovered a protein mediator SON plays a critical role in the health and proper functioning of human embryonic stem cells (hESCs). This finding was reported on 8th September 2013 in the advanced online issue of the prestigious science journal Nature Cell Biology.

Correct expression of genes is essential for a cell to stay alive and to perform other cellular and physiological functions. During gene expression, DNA is first converted into RNA transcript and then some parts of it are removed while others are joined before the trimmed RNA transcript can be translated into proteins. This process of cutting and joining different pieces of RNA is called splicing, and the proteins that mediate splicing are known as splicing factors. Mutations in splicing factors can cause diseases such as myotonic dystrophy and cancer. Even though hESCs have been studied extensively over the last decade due to their potential to differentiate into cell-types of potential clinical applications, little is known about the role that splicing plays in the regulation of pluripotency in these cells.

Scientists at the GIS followed their previous study on a genome-wide investigation of gene functions in hESCs, which was published in Nature [Chia et al. 2010. 468(7321):316-20], and found that splicing factors, such as the protein known as SON, are key regulators of hESC maintenance.

SON was discovered to be essential for converting differentiated cells into pluripotent stem cells[1]. In addition, SON promotes correct splicing of a particular group of RNAs, including those coding for essential hESC regulators, and thereby helps hESCs to survive in an undifferentiated state. Moreover, the authors showed that silencing of SON induced new transcript isoforms[2] that seemed to be non-functional in hESCs.

The study, led by GIS Executive Director Prof Ng Huck Hui, establishes an initial connection between splicing and pluripotency in hESCs and contributes to the comprehensive understanding of the nature of hESCs. Besides its role in hESCs, SON was previously found to be involved in the development of leukemia and influenza virus infection.

Prof Ng Huck Hui said, "Maintenance and differentiation of human embryonic stem cells are governed by an intricate network that comprises diverse cellular processes. In the past, we had been focusing primarily on transcriptional regulation. In our new study, it is clear that splicing contributes to the unique cellular state of hESCs and this can be explained in part through the function of a protein known as SON. SON regulates the precise splicing of specific transcripts which are important for pluripotency. A systematic dissection of the different pathways required for maintenance of pluripotency can eventually guide us in engineering novel cellular states in the laboratory."

"In this new manuscript in Nature Cell Biology, Ng Huck Hui and his colleagues continue to cement their position at the forefront of pluripotency research worldwide," said Dr Alan Colman, the former Executive Director of the Singapore Stem Cell Consortium. "The distinctive feature of human embryonic stem cells is their ability to either self renew or alternatively, given the right conditions, to differentiate into all the cell types that comprise the adult body. In previous work, the team had uncovered a number of unique transcription factors that mediate the maintenance of pluripotency via binding to genomic DNA. In this latest publication, they reveal a novel mechanism where SON, a protein localized to nuclear speckles, regulates the proper splicing of transcripts encoding pluripotency regulators such as OCT4, PRDM14, E4F1 and MED24, and ensures cell survival and maintenance of pluripotency in hESC (and by extrapolation, presumably human induced pluripotent stem cells also)."

Prof Eran Meshorer from the Department of Genetics at the Hebrew University of Jerusalem added, "In recent years, a growing number of papers focusing on the transcriptional regulators that control embryonic stem cell biology have been published. However, the link between RNA splicing and pluripotency has only very recently emerged and the factors that regulate splicing and alternative splicing in ES cells are unknown. The paper by Ng Huck Hui and colleagues now shows that the splicing regulator SON, previously identified in a screen conducted by the same group for novel pluripotency-related factors, regulates the splicing of several key pluripotency genes, linking splicing with stem cell biology and pluripotency. This paper provides a major step towards a more complete understanding of the mechanisms controlling pluripotency and self-renewal, and calls for the identification of additional splicing regulators in ES cells. It is also tempting to speculate that SON and other splicing-related proteins may assist in converting somatic cells into pluripotent cells in the process of reprogramming." Prof Meshorer is the winner of the 2013 Sir Zelman Cowen Universities Fund Prize for Medical Research for the extensive and groundbreaking work undertaken in his laboratory to shed light on pluripotency.

[1] Cells that have the ability to differentiate in different cell types. [2] Different forms of the same gene.

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Singapore Scientists Discover New RNA Processing Pathway Important in Human Embryonic Stem Cells

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Scientists at A*STAR's Genome Institute of Singapore (GIS), in collaboration with their counterparts from Canada, Hong Kong and US, have discovered a protein mediator SON plays a critical role in the health and proper functioning of human embryonic stem cells (hESCs) . This finding was reported on 8th September 2013 in the advanced online issue of the prestigious science journal Nature Cell Biology.

Correct expression of genes is essential for a cell to stay alive and to perform other cellular and physiological functions. During gene expression, DNA is first converted into RNA transcript and then some parts of it are removed while others are joined before the trimmed RNA transcript can be translated into proteins. This process of cutting and joining different pieces of RNA is called splicing, and the proteins that mediate splicing are known as splicing factors. Mutations in splicing factors can cause diseases such as myotonic dystrophy and cancer. Even though hESCs have been studied extensively over the last decade due to their potential to differentiate into cell-types of potential clinical applications, little is known about the role that splicing plays in the regulation of pluripotency in these cells.

Scientists at the GIS followed their previous study on a genome-wide investigation of gene functions in hESCs, which was published in Nature [Chia et al. 2010. 468(7321):316-20], and found that splicing factors, such as the protein known as SON, are key regulators of hESC maintenance.

SON was discovered to be essential for converting differentiated cells into pluripotent stem cells. In addition, SON promotes correct splicing of a particular group of RNAs, including those coding for essential hESC regulators, and thereby helps hESCs to survive in an undifferentiated state. Moreover, the authors showed that silencing of SON induced new transcript isoforms that seemed to be non-functional in hESCs.

The study, led by GIS Executive Director Prof Ng Huck Hui, establishes an initial connection between splicing and pluripotency in hESCs and contributes to the comprehensive understanding of the nature of hESCs. Besides its role in hESCs, SON was previously found to be involved in the development of leukemia and influenza virus infection.

Prof Ng Huck Hui said, "Maintenance and differentiation of human embryonic stem cells are governed by an intricate network that comprises diverse cellular processes. In the past, we had been focusing primarily on transcriptional regulation. In our new study, it is clear that splicing contributes to the unique cellular state of hESCs and this can be explained in part through the function of a protein known as SON. SON regulates the precise splicing of specific transcripts which are important for pluripotency. A systematic dissection of the different pathways required for maintenance of pluripotency can eventually guide us in engineering novel cellular states in the laboratory."

"In this new manuscript in Nature Cell Biology, Ng Huck Hui and his colleagues continue to cement their position at the forefront of pluripotency research worldwide," said Dr Alan Colman, the former Executive Director of the Singapore Stem Cell Consortium. "The distinctive feature of human embryonic stem cells is their ability to either self renew or alternatively, given the right conditions, to differentiate into all the cell types that comprise the adult body. In previous work, the team had uncovered a number of unique transcription factors that mediate the maintenance of pluripotency via binding to genomic DNA. In this latest publication, they reveal a novel mechanism where SON, a protein localized to nuclear speckles, regulates the proper splicing of transcripts encoding pluripotency regulators such as OCT4, PRDM14, E4F1 and MED24, and ensures cell survival and maintenance of pluripotency in hESC (and by extrapolation, presumably human induced pluripotent stem cells also)."

Prof Eran Meshorer from the Department of Genetics at the Hebrew University of Jerusalem added, "In recent years, a growing number of papers focusing on the transcriptional regulators that control embryonic stem cell biology have been published. However, the link between RNA splicing and pluripotency has only very recently emerged and the factors that regulate splicing and alternative splicing in ES cells are unknown. The paper by Ng Huck Hui and colleagues now shows that the splicing regulator SON, previously identified in a screen conducted by the same group for novel pluripotency-related factors, regulates the splicing of several key pluripotency genes, linking splicing with stem cell biology and pluripotency. This paper provides a major step towards a more complete understanding of the mechanisms controlling pluripotency and self-renewal, and calls for the identification of additional splicing regulators in ES cells. It is also tempting to speculate that SON and other splicing-related proteins may assist in converting somatic cells into pluripotent cells in the process of reprogramming." Prof Meshorer is the winner of the 2013 Sir Zelman Cowen Universities Fund Prize for Medical Research for the extensive and groundbreaking work undertaken in his laboratory to shed light on pluripotency.

Explore further: Researchers ID proteins key in stem cell production

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Scientists discover new RNA processing pathway important in human embryonic stem cells

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/82v6t2/cancer_stem_cells) has announced the addition of the "Cancer Stem Cells Drug Pipeline Update 2013" report to their offering.

Treatments designed to target and destroy cancer stem cells may come to revolutionize how we treat cancer. This unique product covers both explicit cancer stem cell drug development and cancer drugs which are inhibitors of the Hedgehog, Notch, and WNT Pathway. These developmental pathways are frequently activated in neoplasms, and particularly in the rare subpopulation of cancer stem cells.

There are today 308 companies plus partners developing 478 cancer stem cells and developmental pathways drugs in 1568 developmental projects in cancer. In addition, there are 6 suspended drugs and the accumulated number of ceased drugs over the last years amount to another 232 drugs. Cancer Stem Cells Drug Pipeline Update lists all drugs and gives you a progress analysis on each one of them. Identified drugs are linked to 257 different targets. All included targets have been cross-referenced for the presence of mutations associated with human cancer. To date 250 out of the 253 studied drug targets so far have been recorded with somatic mutations.

All drugs targets are further categorized on in the software application by 49 classifications of molecular function and with pathway referrals to BioCarta, KEGG, NCI-Nature and NetPath.

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Pipeline Breakdown According to Number of Drugs

For more information visit http://www.researchandmarkets.com/research/82v6t2/cancer_stem_cells

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Research and Markets: Cancer Stem Cells Drug Pipeline Update 2013

AVN Treatment using stem cells Patient #39;s Testimonials
Avascular necrosis (also osteonecrosis, bone infarction, aseptic necrosis, ischemic bone necrosis, and AVN) is a disease where there is cellular death (necro...

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AVN Treatment using stem cells Patient's Testimonials - Video

TORONTO Canadian researchers have treated the first patient in a clinical trial using

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TORONTO Canadian researchers have treated the first patient in a clinical trial using genetically enhanced stem cells to repair damaged heart muscle after a major heart attack.

The experimental therapy uses stem cells extracted from a patients blood soon after their heart attack.

The cells are enhanced with a gene that stimulates blood vessel growth and improves tissue healing, then infused into the patients heart.

Principal investigator Dr. Duncan Stewart says the goal is to stimulate repair, reduce scar tissue and restore the hearts ability to pump blood efficiently.

The trial will enrol 100 patients over two years, starting with patients at the University of Ottawa Heart Institute and St. Michaels Hospital in Toronto.

A third of the participants will receive genetically enhanced stem cells, a third non-enhanced stem cells and a third a placebo.

Stem cells have incredible potential to repair and regenerate damaged organs, but cells that come from heart attack patients dont have the same healing abilities as those from young, healthy adults, said Stewart, CEO and scientific director of the Ottawa Hospital Research Institute.

Our strategy is to rejuvenate these stem cells by providing extra copies of a gene that is essential for their regenerative activity to help the heart fix itself.

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Study begun to see if genetically enhanced stem cells can repair heart attack damage

Washington, Sept. 05 (ANI): Researchers have found that stem cells in cortical, or compact, bone do a better job when it comes to the regeneration of heart tissue than the heart's own stem cells.

The findings by senior investigator, Steven R. Houser, at Temple University School of Medicine's Cardiovascular Research Center (CVRC), have considerable implications for stem cell therapy for the heart.

Stem cells are youthful by degrees, and cortical bone-derived stem cells (CBSCs) are considered some of the most pluripotent - like human newborns, naive and ready to become anything. But while CBSCs and similarly pluripotent stem cells retain the ability to develop into any cell type needed by the body and sometimes bring their youthful energy to the aid of mature cells - making them especially appealing for therapeutics - they also have the potential to wander off course, possibly landing themselves in unintended tissues.

To figure out how CBSCs might behave in the heart in the first place, Houser's team began by collecting the cells from mouse tibias. The particular mice used had been engineered with green fluorescent protein (GFP), which meant that the CBSCs carried a green marker to allow for their later identification. The cells were then expanded in petri dishes in the laboratory before being injected directly into the hearts of non-GFP mice that had suffered heart attacks. Some mice received cardiac stem cells instead of CBSCs.

The findings challenge the general assumption that cardiac stem cells, because they reside in the heart, are the cells most capable of repairing damaged heart tissue.

The study is published in the journal Circulation Research. (ANI)

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'Youthful' stem cells from bone can regenerate heart tissue

Sheryl Ubelacker, The Canadian Press Published Thursday, September 5, 2013 11:29AM EDT Last Updated Thursday, September 5, 2013 3:06PM EDT

Canadian researchers have begun a trial using genetically enhanced stem cells in the hope they can repair a patient's heart muscle after a major heart attack.

The researchers, who announced the start of the study Thursday in Ottawa, believe they are the first in the world to test genetically boosted stem cells as a possible means of rejuvenating severely damaged heart muscle.

The experimental therapy uses stem cells extracted from a patient's blood within days to a few weeks after a major heart attack, said principal investigator Dr. Duncan Stewart, CEO and scientific director of the Ottawa Hospital Research Institute.

Scientists enhance these progenitor cells with a gene called endothelial nitric oxide synthase, which is known to stimulate blood vessel growth and improve tissue healing. These beefed-up stem cells are then infused into the patient's heart through the coronary artery involved in the heart attack.

"Stem cells have incredible potential to repair and regenerate damaged organs, but cells that come from heart attack patients don't have the same healing abilities as those from young, healthy adults," said Stewart. The cells are as old as the patient and have been exposed to the same factors that led to the heart attack.

"Our strategy is to rejuvenate these stem cells by providing extra copies of a gene that is essential for their regenerative activity, so that they better stimulate heart repair, reduce scar tissue and restore the heart's ability to pump blood efficiently -- in other words to help the heart fix itself."

Harriet Garrow, who suffered a major heart attack in July, is the first patient to have been treated as part of the two-year trial, which will enrol 100 patients at a number of centres in Canada, starting the University of Ottawa Heart Institute and St. Michael's Hospital in Toronto. Other hospitals in Montreal and Toronto will be added.

Garrow, 68, isn't sure which therapy she received. The study is a double-blind, randomized control trial, meaning that patients are randomly selected to get one of three treatments -- the genetically enhanced stem cells, non-enhanced stem cells or a placebo preparation.

Blinding means neither the patient nor the researcher administering the therapy knows which one is being used.

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Canadian researchers exploring: Can gene-enhanced stem cells repair heart attack damage?

Sep. 4, 2013 Many people who survive a heart attack find themselves back in the hospital with a failing heart just years later. And the outcome often is unfavorable, owing to limited treatment options. But scientists at Temple University School of Medicine's Cardiovascular Research Center (CVRC) recently found hope in an unlikely source -- stem cells in cortical, or compact, bone. In a new study, they show that when it comes to the regeneration of heart tissue, these novel bone-derived cells do a better job than the heart's own stem cells.

According to the study's senior investigator, Steven R. Houser, Ph.D., FAHA, Chairperson of Temple's Department of Physiology and Director of the CVRC, it is early days for cortical bone-derived stem cells (CBSCs). Nonetheless, his team's findings, featured on the cover of the August 16th issue of Circulation Research, have considerable implications for stem cell therapy for the heart.

A major challenge in the treatment of heart attack is early intervention, which is key to reducing the chances for long-term complications, such as heart failure. When it comes to stem cells, Houser said, "The strategy is to inject the cells right after [a heart attack]." Currently, though, that approach works only in animal studies. To make it work in humans, Houser explained, "we need cells right off the rack and ready to go clinically."

CBSCs could be those cells. Stem cells are youthful by degrees, and CBSCs are considered some of the most pluripotent -- like human newborns, nave and ready to become anything. But while CBSCs and similarly pluripotent stem cells retain the ability to develop into any cell type needed by the body and sometimes bring their youthful energy to the aid of mature cells -- making them especially appealing for therapeutics -- they also have the potential to wander off course, possibly landing themselves in unintended tissues. Cardiac stem cells, on the other hand, are a little more capable and a little more set in their ways, like toddlers. While they may need some coaxing into action, they are more likely to stay in their resident tissue.

To figure out how CBSCs might behave in the heart in the first place, Houser's team, led by Temple graduate student Jason Duran, began by collecting the cells from mouse tibias. The particular mice used had been engineered with green fluorescent protein (GFP), which meant that the CBSCs carried a green marker to allow for their later identification. The cells were then expanded in petri dishes in the laboratory before being injected directly into the hearts of non-GFP mice that had suffered heart attacks. Some mice received cardiac stem cells instead of CBSCs.

In the following weeks, as the team monitored the progress of the mice, they found that the youthfulness of the CBSCs had prevailed. The cells had triggered the growth of new blood vessels in the injured tissue, and six weeks after injection, they had differentiated, or matured, into heart muscle cells. While generally smaller than native heart cells, the new cells had the same functional capabilities, and overall they had improved survival and heart function. Similar improvements were not observed in the subset of mice treated with cardiac stem cells. Nor was there evidence in those mice that the cardiac cells had undergone differentiation.

The findings challenge the general assumption that cardiac stem cells, because they reside in the heart, are the cells most capable of repairing damaged heart tissue. For that reason, according to Houser, the new paper likely will be controversial.

"What we did generates as many questions as it does answers," he said. "Cell therapy attempts to repopulate the heart with new heart cells. But which cells should be used, and when they should be put into the heart are among many unanswered questions."

To address at least some of those questions, Houser's team plans next to investigate CBSCs in a large-animal heart attack model. If that study yields similar results as the first, the cells could be ushered into a small-scale clinical trial of human patients. In humans, CBSCs would be collected from bone using techniques akin to those employed for bone marrow aspiration, a much simpler process than that used to isolate cardiac stem cells. While the cells would originate from a different person, raising the risk of rejection by the patient's immune system, it may be possible to have them at the ready in hospital settings, allowing for their injection immediately after a heart attack.

The cell therapy work by Houser's team represents just one of several forms of heart therapy being explored at Temple's CVRC. According to Houser, "Temple has made a commitment to cardiovascular research, with a clinical enterprise focused on treating patients. We're trying anything and everything to repair the heart [safely]." Other avenues of research include gene therapy, drug therapy, and the use of novel biomaterials to more effectively deliver drugs.

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Youthful stem cells from bone can heal the heart

Public release date: 4-Sep-2013 [ | E-mail | Share ]

Contact: Jeremy Walter Jeremy.Walter@tuhs.temple.edu 215-707-7882 Temple University Health System

(Philadelphia, PA) - Many people who survive a heart attack find themselves back in the hospital with a failing heart just years later. And the outcome often is unfavorable, owing to limited treatment options. But scientists at Temple University School of Medicine's Cardiovascular Research Center (CVRC) recently found hope in an unlikely source stem cells in cortical, or compact, bone. In a new study, they show that when it comes to the regeneration of heart tissue, these novel bone-derived cells do a better job than the heart's own stem cells.

According to the study's senior investigator, Steven R. Houser, Ph.D., FAHA, Chairperson of Temple's Department of Physiology and Director of the CVRC, it is early days for cortical bone-derived stem cells (CBSCs). Nonetheless, his team's findings, featured on the cover of the August 16th issue of Circulation Research, have considerable implications for stem cell therapy for the heart.

A major challenge in the treatment of heart attack is early intervention, which is key to reducing the chances for long-term complications, such as heart failure. When it comes to stem cells, Houser said, "The strategy is to inject the cells right after [a heart attack]." Currently, though, that approach works only in animal studies. To make it work in humans, Houser explained, "we need cells right off the rack and ready to go clinically."

CBSCs could be those cells. Stem cells are youthful by degrees, and CBSCs are considered some of the most pluripotent like human newborns, nave and ready to become anything. But while CBSCs and similarly pluripotent stem cells retain the ability to develop into any cell type needed by the body and sometimes bring their youthful energy to the aid of mature cells making them especially appealing for therapeutics they also have the potential to wander off course, possibly landing themselves in unintended tissues. Cardiac stem cells, on the other hand, are a little more capable and a little more set in their ways, like toddlers. While they may need some coaxing into action, they are more likely to stay in their resident tissue.

To figure out how CBSCs might behave in the heart in the first place, Houser's team, led by Temple graduate student Jason Duran, began by collecting the cells from mouse tibias. The particular mice used had been engineered with green fluorescent protein (GFP), which meant that the CBSCs carried a green marker to allow for their later identification. The cells were then expanded in petri dishes in the laboratory before being injected directly into the hearts of non-GFP mice that had suffered heart attacks. Some mice received cardiac stem cells instead of CBSCs.

In the following weeks, as the team monitored the progress of the mice, they found that the youthfulness of the CBSCs had prevailed. The cells had triggered the growth of new blood vessels in the injured tissue, and six weeks after injection, they had differentiated, or matured, into heart muscle cells. While generally smaller than native heart cells, the new cells had the same functional capabilities, and overall they had improved survival and heart function. Similar improvements were not observed in the subset of mice treated with cardiac stem cells. Nor was there evidence in those mice that the cardiac cells had undergone differentiation.

The findings challenge the general assumption that cardiac stem cells, because they reside in the heart, are the cells most capable of repairing damaged heart tissue. For that reason, according to Houser, the new paper likely will be controversial.

"What we did generates as many questions as it does answers," he said. "Cell therapy attempts to repopulate the heart with new heart cells. But which cells should be used, and when they should be put into the heart are among many unanswered questions."

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Youthful stem cells from bone can heal the heart, Temple scientists report

San Diego, CA (PRWEB) September 03, 2013

Histogen, Inc., a regenerative medicine company developing innovative therapies for conditions including hair loss and cancer, today announced that the United States Patent & Trademark Office has issued patent 8,524,494, entitled Low Oxygen Tension and bFGF Generates a Multipotent Stem Cell from a Fibroblast In Vitro to the Company.

The issued patent covers Histogens method of triggering the de-differentiation of fibroblast cells into multipotent stem cells through low oxygen and special culture conditions. The resulting multipotent cells naturally secrete a variety of soluble and insoluble molecules that are the basis for Histogens products.

Histogens process is uniquely capable of harnessing all of the benefits and excitement of stem cell therapies without any of the ethical, safety or sourcing concerns, said Dr. Gail K. Naughton, Histogen CEO and Chairman of the Board. Issuance of this patent adds great strength to our technology, and value to our partners and products.

Current stem cell-derived therapies utilize embryonic stem cells or genetically-manipulated induced pluripotent stem cells, both of which have an inherent ethical and scientific risk, and raise a number of regulatory issues. Still, enthusiasm continues to build around stem cells, both for their potential to address serious medical conditions as well as their aesthetic benefits for beauty and rejuvenation.

Through Histogens technology process, the Company is uniquely able to begin with newborn fibroblasts cells, a safe, well-established and non-controversial cell source, and convert the cells into multipotent stem cells without genetic manipulation. The cells express key stem cell markers including Oct4, Sox2 and Nanog, and secrete a distinctive composition of growth factors and other proteins known to stimulate stem cells in the body, regenerate tissues, and promote scarless healing.

It is the soluble and insoluble compositions of multipotent proteins and growth factors which make up Histogens products, with numerous applications. Histogens lead product, Hair Stimulating Complex (HSC) has shown success in two Company-sponsored clinical trials as an injectable treatment for alopecia. In addition, the human multipotent cell conditioned media produced through Histogens process can be found in the ReGenica line of skincare products, currently being distributed by Suneva Medical in partnership with Obagi Medical Products. Further indications of the materials currently being developed include oncology and orthopedics.

About Histogen Histogen is a regenerative medicine company developing solutions based upon the products of cells grown under proprietary conditions that mimic the embryonic environment, including low oxygen and suspension. Through this unique technology process, newborn cells are encouraged to naturally produce the vital proteins and growth factors from which the Company has developed its rich product portfolio. Histogens technology focuses on stimulating a patients own stem cells by delivering a proprietary complex of multipotent human proteins that have been shown to support stem cell growth and differentiation. For more information, please visit http://www.histogen.com.

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Histogen’s Method of Generating Multipotent Stem Cells Receives US Patent