On Monday, a group of scientists at Cedars-Sinai Heart Institute in Los Angeles, CA, discovered througha world-first experimenta form to rejuvenate elder rats old hearts by injecting cardiac stem cells from much younger rats with healthier hearts. They hope this process might eventually become useful to humans.

The first time an experiment like this was carried out was in 2009 by the same Los Angeles-based team. Now, they also proved the possibility of reversing aging in old hearts.

Heart failure is a typical cause of death in humans. Around 48 percent of women and 46 percent of men die a year from heart attacks and other heart-related diseases. They are the first reason of death worldwide, and a leading cause of death in the United States, killing over 375,000 Americans a year. Nearly half of all African-American population suffers from heart diseases.

Researchers took stem cells from the hearts of 4-month-old rats, shaped them into cardiosphere-derived cells and injected them into the hearts of other rats of 22 monthsold, an age that makes them be considered as old. They carried out a similar process to another group of rats but injected saline instead. Scientists later compared both groups.

After receiving the stem cells injection, researchers noted a significant change in the way old rats continued to live. They turned much more active and improved their functionalities. Not just their heart rates got better and faster, but also the way they ran and breathed. Their hair started to grow faster, their chromosomal telomeres which commonly shrink with age lengthened, plus other benefits. The rodents began to progressively improve their capacity of exercise along with their stamina overall.

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, said Dr Eduardo Marbn, director of the Cedars-Sinai Heart Institute and lead author, who is also extremely excited for having witnessed the unexpected fountain of youth.

In 2009, his team successfully repaired the damaged heart of a man who had suffered a heart attack, using his own heart tissue.

Stem cells are a really basic type of cells that can be molded and converted into other much-specialized cells through a process called differentiation, which is basicallyshaping them into any kind of body cell.They form in embryos like embryonic stem cells -, which help in the growth process of babies, along with the millions of other different cell types they need before their birth.

One of many cells scientists generated from stem cells is called progenitor cell, which shares some of the same properties. But unlike the original cells, progenitor cells are not able to divide and reproduce indefinitely. Dr. Marbn also said they discovered cardiosphere-derived cells, which tend to promote the healing of a condition that affects more than 50 percent of patients suffering from heart failure.

Our previous lab studies and human clinical trials have shown promise in treating heart failure using cardiac stem cell infusions, said Dr Marbn. Now we find that these specialized stem cells could turn out to reverse problems associated with aging of the heart.

According to Dr. Marbn, stem cells secrete exosomes, tiny vesicles which contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injuries, and the way genes are expressed in the tissue. They are placed into the heart, and act to transform it into a better organ, helping it at the same time to improve exercise capacity and hair regrowth, he explained.

Now, Dr. Marbn is exploring a much easier way to deliver the stem cells intravenously, instead of injecting them directly into the heart. Thus avoiding surgeries, which tend to be more complicated and expensive for the patient.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Now, scientistsneed to make more extensive studies before using the technique in humans.

Source: CNN

See the article here:
Scientists discovered how to rejuvenate rats by injecting stem cells ... - Pulse Headlines

Cardiac Stem Cells Comments Off on Scientists discovered how to rejuvenate rats by injecting stem cells … – Pulse Headlines | August 19th, 2017

The early heart tube of a chick embryo: cardiac and endothelial cells are made visible by specifically expressing fluorescent proteins under the control of the Nkx2.5 (green) and Isl1 (red) cardiovascular genes. Credit: Weizmann Institute of Science

One of the first organ systems to form and function in the embryo is the cardiovascular system: in fact, this developmental process starts so early that scientists still have many unresolved questions on the origin of the primitive heart and blood vessels. How do the first cells the progenitors that are destined to become part of this system participate in shaping the developed cardiovascular system?

Dr. Lyad Zamir, a former PhD student in the lab of Prof. Eldad Tzahor in the Weizmann Institute of Science's Department of Molecular Cell Biology, developed a method to image the earliest cardiovascular progenitors and track them and their descendants through the developing embryo in real time. His movies took place in fertilized chicken eggs, in which a complex network of blood vessels forms within the yolk sac to nourish the embryo. The findings of this research were recently published in eLife.

Working in collaboration with the lab of Prof. Richard Harvey of the Victor Chang Cardiac Research Institute and the University of New South Wales, both in Australia, Prof. Tzahor and Dr. Zamir focused on a gene called Nkx2-5. This gene encodes a transcription factor, which is a regulatory protein that controls the expression of other genes involved in the development of the heart. "The new study revealed that Nkx2-5, independently of its role in the development of the heart, plays a central role in the genesis of the very first blood vessels and indeed the formation of blood," says Prof. Tzahor.

Looking at the onset of Nkx2-5 expression, the team revealed the existence of progenitor cells called hemangioblasts. These cells give rise to both the blood and vascular progenitor cells those that lead to the formation of blood vessels. These unique cells are created from the mesoderm the middle layer of cells that appears in the very early developing embryo. Researchers have been hotly debating the existence of hemangioblasts and, if they do exist, their possible function.

In the chick embryo films, the researchers could see the hemangioblasts moving to create "blood islands," which form within the primitive embryonic vessels. The researchers were surprised to observe that some of the hemangioblast cells were moving into the heart, where they formed blood stem cells. This helped make sense of other studies revealing that the early heart tube contains cells that appear to assist in generating blood cells. The researchers also identified specialized Nkx2-5-expressing cells within the lining of the newly formed aorta, where they appeared to "bud off" to produce new blood cells. Later on in development, these specialized cells move into the liver, where they give rise to the blood-forming stem cells in the fetus.

Prof. Tzahor: "Even 20 years after one of the 'master genes' for heart development was discovered, we have managed to write a new story about its action, showing that it works briefly at a very early stage in development in the formation of vessels and blood before the main action takes place in the heart. We have provided solid evidence for the existence of these very early cells and their contribution to heart and vascular development."

Because these findings reveal the early origins of at least some of the blood-forming stem cells in the embryo, they may be especially helpful in research into diseases affecting the cardiovascular system.

Explore further: Kidney research leads to surprising discovery about how the heart forms

More information: Lyad Zamir et al. Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta, eLife (2017). DOI: 10.7554/eLife.20994

Read more:
The unexpected role of a well-known gene in creating blood - Medical Xpress

Cardiac Stem Cells Comments Off on The unexpected role of a well-known gene in creating blood – Medical Xpress | August 16th, 2017

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats' fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

"It's extremely exciting," said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing "the systemic rejuvenating effects," he said, "it's kind of like an unexpected fountain of youth."

"We've been studying new forms of cell therapy for the heart for some 12 years now," Marbn said.

Some of this research has focused on cardiosphere-derived cells.

"They're progenitor cells from the heart itself," Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem "that's very typical of what we find in older human beings: The heart's stiff, and it doesn't relax right, and it causes fluid to back up some," Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats -- that's elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

"The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I'm kind of losing my hair) the animals ... regrew their fur a lot better after they'd gotten cells" compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

Why did it work?

The working hypothesis is that the cells secrete exosomes, tiny vesicles that "contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue," Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he's begun to explore delivering the cardiac stem cells intravenously in a simple infusion -- instead of injecting them directly into the heart, which would be a complex procedure for a human patient -- and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is "very comprehensive."

"Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems," said Gerstenblith, who did not contribute to the new research. "The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly."

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has "led the field in this area."

"The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they've seen in the past," said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells "from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue," Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

"We need to make sure there's no harm being done," Herron said, adding that extending the lifetime and improving quality of life amounts to "a tradeoff between the potential risk and the potential good that can be done."

Capicor hasn't announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven "completely safe" in "over 100 human patients," so it would be possible to fast-track them into the clinic, Marbn explained: "I can't tell you that there are any plans to do that, but it could easily be done from a safety viewpoint."

Read more:
Cardiac stem cells rejuvenate rats' aging hearts, study says - CNN

Cardiac Stem Cells Comments Off on Cardiac stem cells rejuvenate rats’ aging hearts, study says – CNN | August 16th, 2017

Cardiac stem cells derived from young hearts helped reverse the signs of aging when directly injected into the old hearts of elderly rats, astudypublished Monday in the European Heart Journal demonstrated.

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

Its extremely exciting, said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing the systemic rejuvenating effects, he said, its kind of like an unexpected fountain of youth.

Weve been studying new forms of cell therapy for the heart for some 12 years now, Marbn said.

Some of this research has focused on cardiosphere-derived cells.

Theyre progenitor cells from the heart itself, Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

From hisown previous research, Marbn discovered that cardiosphere-derived cells promote the healing of the heart after a condition known as heart failure with preserved ejection fraction, which affects more than 50% of all heart failure patients.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem thats very typical of what we find in older human beings: The hearts stiff, and it doesnt relax right, and it causes fluid to back up some, Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats thats elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

The working hypothesis is that the cells secrete exosomes, tiny vesicles that contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue, Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said hes begun to explore delivering the cardiac stem cells intravenously in a simple infusion instead of injecting them directly into the heart, which would be a complex procedure for a human patient and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is very comprehensive.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Gerstenblith, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Todd Herron, director of the University of Michigan Frankel Cardiovascular Centers Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has led the field in this area.

The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon theyve seen in the past, said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue, Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

We need to make sure theres no harm being done, Herron said, adding that extending the lifetime and improving quality of life amounts to a tradeoff between the potential risk and the potential good that can be done.

Capicor, the company that grows these special cells, is focused solely on therapies for muscular dystrophy and heart failure with ongoing clinical trials involving human patients, Marbn said.

Capicor hasnt announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven completely safe in over 100 human patients, so it would be possible to fast-track them into the clinic, Marbn explained: I cant tell you that there are any plans to do that, but it could easily be done from a safety viewpoint.

More here:
'Unexpected fountain of youth' found in cardiac stem cells, says researcher - fox6now.com

Cardiac Stem Cells Comments Off on ‘Unexpected fountain of youth’ found in cardiac stem cells, says researcher – fox6now.com | August 15th, 2017

Cardiac stem cells derived from young hearts helped reverse the signs of aging when directly injected into the old hearts of elderly rats, astudypublished Monday in the European Heart Journal demonstrated.

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

Its extremely exciting, said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing the systemic rejuvenating effects, he said, its kind of like an unexpected fountain of youth.

Weve been studying new forms of cell therapy for the heart for some 12 years now, Marbn said.

Some of this research has focused on cardiosphere-derived cells.

Theyre progenitor cells from the heart itself, Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

From hisown previous research, Marbn discovered that cardiosphere-derived cells promote the healing of the heart after a condition known as heart failure with preserved ejection fraction, which affects more than 50% of all heart failure patients.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem thats very typical of what we find in older human beings: The hearts stiff, and it doesnt relax right, and it causes fluid to back up some, Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats thats elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

The working hypothesis is that the cells secrete exosomes, tiny vesicles that contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue, Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said hes begun to explore delivering the cardiac stem cells intravenously in a simple infusion instead of injecting them directly into the heart, which would be a complex procedure for a human patient and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is very comprehensive.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Gerstenblith, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Todd Herron, director of the University of Michigan Frankel Cardiovascular Centers Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has led the field in this area.

The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon theyve seen in the past, said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue, Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

We need to make sure theres no harm being done, Herron said, adding that extending the lifetime and improving quality of life amounts to a tradeoff between the potential risk and the potential good that can be done.

Capicor, the company that grows these special cells, is focused solely on therapies for muscular dystrophy and heart failure with ongoing clinical trials involving human patients, Marbn said.

Capicor hasnt announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven completely safe in over 100 human patients, so it would be possible to fast-track them into the clinic, Marbn explained: I cant tell you that there are any plans to do that, but it could easily be done from a safety viewpoint.

Continued here:
Unexpected fountain of youth found in cardiac stem cells ...

Cardiac Stem Cells Comments Off on Unexpected fountain of youth found in cardiac stem cells … | August 15th, 2017

On Monday, a group of scientists at Cedars-Sinai Heart Institute in Los Angeles, CA, discovered througha world-first experimenta form to rejuvenate elder rats old hearts by injecting cardiac stem cells from much younger rats with healthier hearts. They hope this process might eventually become useful to humans.

The first time an experiment like this was carried out was in 2009 by the same Los Angeles-based team. Now, they also proved the possibility of reversing aging in old hearts.

Heart failure is a typical cause of death in humans. Around 48 percent of women and 46 percent of men die a year from heart attacks and other heart-related diseases. They are the first reason of death worldwide, and a leading cause of death in the United States, killing over 375,000 Americans a year. Nearly half of all African-American population suffers from heart diseases.

Researchers took stem cells from the hearts of 4-month-old rats, shaped them into cardiosphere-derived cells and injected them into the hearts of other rats of 22 monthsold, an age that makes them be considered as old. They carried out a similar process to another group of rats but injected saline instead. Scientists later compared both groups.

After receiving the stem cells injection, researchers noted a significant change in the way old rats continued to live. They turned much more active and improved their functionalities. Not just their heart rates got better and faster, but also the way they ran and breathed. Their hair started to grow faster, their chromosomal telomeres which commonly shrink with age lengthened, plus other benefits. The rodents began to progressively improve their capacity of exercise along with their stamina overall.

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, said Dr Eduardo Marbn, director of the Cedars-Sinai Heart Institute and lead author, who is also extremely excited for having witnessed the unexpected fountain of youth.

In 2009, his team successfully repaired the damaged heart of a man who had suffered a heart attack, using his own heart tissue.

Stem cells are a really basic type of cells that can be molded and converted into other much-specialized cells through a process called differentiation, which is basicallyshaping them into any kind of body cell.They form in embryos like embryonic stem cells -, which help in the growth process of babies, along with the millions of other different cell types they need before their birth.

One of many cells scientists generated from stem cells is called progenitor cell, which shares some of the same properties. But unlike the original cells, progenitor cells are not able to divide and reproduce indefinitely. Dr. Marbn also said they discovered cardiosphere-derived cells, which tend to promote the healing of a condition that affects more than 50 percent of patients suffering from heart failure.

Our previous lab studies and human clinical trials have shown promise in treating heart failure using cardiac stem cell infusions, said Dr Marbn. Now we find that these specialized stem cells could turn out to reverse problems associated with aging of the heart.

According to Dr. Marbn, stem cells secrete exosomes, tiny vesicles which contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injuries, and the way genes are expressed in the tissue. They are placed into the heart, and act to transform it into a better organ, helping it at the same time to improve exercise capacity and hair regrowth, he explained.

Now, Dr. Marbn is exploring a much easier way to deliver the stem cells intravenously, instead of injecting them directly into the heart. Thus avoiding surgeries, which tend to be more complicated and expensive for the patient.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Now, scientistsneed to make more extensive studies before using the technique in humans.

Source: CNN

Read more here:
Scientists discovered how to rejuvenate rats by injecting stem cells into their hearts - Pulse Headlines

Cardiac Stem Cells Comments Off on Scientists discovered how to rejuvenate rats by injecting stem cells into their hearts – Pulse Headlines | August 15th, 2017

SOUTH SAN FRANCISCO, CA--(Marketwired - August 14, 2017) - VistaGen Therapeutics Inc. (NASDAQ: VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, today reported its financial results for its first fiscal quarter ended June 30, 2017.

The Company also provided an update on its corporate progress, clinical status and anticipated milestones for AV-101, its orally available CNS prodrug candidate in Phase 2 development, initially as a new generation treatment for major depressive disorder (MDD).

"We anticipate several catalytic milestones in our clinical development, intellectual property and regulatory programs for AV-101 within the next 6 to 18 months. We remain highly focused on satisfying standard regulatory requirements and completing preparations for our planned AV-101 Phase 2 adjunctive treatment study in MDD. Our primary goal is to launch the study in January 2018 and complete it during 2018 to advance our efforts to provide a new generation treatment alternative to millions battling depression every day," commented Shawn Singh, Chief Executive Officer of VistaGen.

Mr. Singh continued, "In conjunction with our focused efforts to advance our AV-101 Phase 2 development program, we have continued to expand our intellectual property portfolio. Earlier this year the European Patent Office issued a Notice of Intention to Grant our European Patent Application regarding AV-101 for treatment of depression and reduction of dyskinesias associated with levodopa therapy for Parkinson's disease, a patent that will be in effect until at least January 2034. In addition, the U.S. Patent and Trademark Office recently allowed another important U.S. patent relating to stem cell technology held by VistaStem Therapeutics, our subsidiary using stem cell technology for drug rescue and regenerative medicine. The breakthrough technology under the allowed U.S. patent involves the stem cells from which all blood cells and most bone marrow cells are derived, technology with the potential to reach patients with a broad range of life-threatening diseases, including cancer, with CAR-T cell applications and foundational technology we believe may ultimately provide approaches for producing bone marrow stem cells for bone marrow transfusions. We are confident in our path forward through strategic collaborations, such as our agreement with the U.S. National Institute of Mental Health covering its full financial sponsorship of the ongoing Phase 2 study of AV-101 for MDD that Dr. Carlos Zarate Jr. and his team are conducting at the NIH's clinic in Bethesda, as well as our sublicense arrangement with BlueRock Therapeutics, a company established by Bayer AG and Versant Ventures, focused on regenerative medicine for heart disease. As we have historically, we believe we have surrounded ourselves with partners, supportive stockholders and corporate development and finance experts who share our confidence in our future and will assist us in securing key collaborations and raising sufficient capital to achieve our objectives, most notably the launch and completion in 2018 of our Phase 2 adjunctive treatment study of AV-101 for MDD. We look forward to creating value for our stakeholders in fiscal 2018 and beyond."

Potential Near-Term Milestones:

During the second half of 2017, the Company is pursuing the following objectives:

Further, the Company anticipates that the U.S. National Institute of Mental Health (NIMH) will complete the NIH-sponsored Phase 2 study of AV-101 in depression, with topline results during the first half of 2018.

Recent Operational Highlights:

Advancement of AV-101 as a Potential, Non-Opioid Treatment Alternative for Chronic Pain

Bolstered Clinical Team with Industry Expert

Intellectual Property Accomplishments

Capital Market Highlights

Financial Results for the Fiscal Quarter Ended June 30, 2017:

At June 30, 2017, the Company had a cash and cash equivalents balance of $1.6 million, compared to $2.9 million as of March 31, 2017. Between late-March 2017 and late-June 2017, in self-placed private placement transactions, the Company sold units consisting of unregistered common stock and common stock warrants to accredited investors, yielding approximately $1 million in net cash proceeds.

Net loss for the fiscal quarters ended June 30, 2017 and 2016 was approximately $2.3 million and $2.0 million, respectively, including non-cash expenses of approximately $0.5 million in each period.

Research and development expense totaled $1.1 million for the fiscal quarter ended June 30, 2017, compared with $0.8 million for the fiscal quarter ended June 30, 2016. The increase in year-over-year research and development expense was attributable to the Company's increased focus on the continuing non-clinical and clinical development of AV-101 and ongoing preparations to launch its AV-101 Phase 2 Adjunctive Treatment Study.

General and administrative expense increased slightly to $1.2 million in the fiscal quarter ended June 30, 2017, from $1.1 million in the fiscal quarter ended June 30, 2016 primarily because of increased headcount and employee-related expenses and non-cash stock compensation expense attributable to recent stock option grants, partially offset by a reduction in professional services fees.

About VistaGen

VistaGen Therapeutics, Inc. (NASDAQ: VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other CNS disorders. VistaGen's lead CNS product candidate, AV-101, is in Phase 2 development, initially as a new generation oral antidepressant prodrug candidate for MDD. AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. NIMH in a Phase 2 monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 180-patient Phase 2 study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressants. Dr. Maurizio Fava of Harvard Medical School will be the Principal Investigator of the Company's Phase 2 adjunctive treatment study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including neuropathic pain, epilepsy, Huntington's disease, L-Dopa-induced dyskinesia associated with Parkinson's disease and other disorders where modulation of the NMDA receptors, activation of AMPA pathways and/or key active metabolites of AV-101 may achieve therapeutic benefit.

About VistaStem

VistaStem Therapeutics is VistaGen's wholly-owned subsidiary focused on applying human pluripotent stem cell (hPSC) technology, internally and with third-party collaborators, to discover, rescue, develop and commercialize (i) proprietary new chemical entities (NCEs), including NCEs with regenerative potential, for CNS and other diseases and (ii) cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. VistaStem's internal drug rescue programs are designed to utilize CardioSafe 3D, its customized cardiac bioassay system, to develop NCEs for VistaGen's pipeline. To advance potential regenerative medicine (RM) applications of its cardiac stem cell technology, in December 2016, VistaStem exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established in 2016 by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac cells for the treatment of heart disease. In a manner similar to its exclusive sublicense agreement with BlueRock Therapeutics, VistaStem may pursue additional collaborations and potential RM applications of its stem cell technology platform, including using blood, cartilage, and/or liver cells derived from hPSCs, for (i) cell-based therapy, (ii) cell repair therapy, and/or (iii) tissue engineering.

For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking Statements

The statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2 (monotherapy) and/or the Company's planned Phase 2 (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, including neuropathic pain and levodopa (L-DOPA)-induced dyskinesia associated with Parkinson's disease, the potential for the Company's stem cell technology to produce NCEs, cellular therapies, regenerative medicine or bone marrow stem cells to treat any medical condition, including autoimmune disorders and cancer, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the AV-101 clinical development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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VistaGen Therapeutics Reports First Fiscal Quarter 2018 Financial Results and Provides Business Update - Marketwired (press release)

Cardiac Stem Cells Comments Off on VistaGen Therapeutics Reports First Fiscal Quarter 2018 Financial Results and Provides Business Update – Marketwired (press release) | August 14th, 2017

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats' fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

"It's extremely exciting," said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing "the systemic rejuvenating effects," he said, "it's kind of like an unexpected fountain of youth."

"We've been studying new forms of cell therapy for the heart for some 12 years now," Marbn said.

Some of this research has focused on cardiosphere-derived cells.

"They're progenitor cells from the heart itself," Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem "that's very typical of what we find in older human beings: The heart's stiff, and it doesn't relax right, and it causes fluid to back up some," Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats -- that's elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

"The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I'm kind of losing my hair) the animals ... regrew their fur a lot better after they'd gotten cells" compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

Why did it work?

The working hypothesis is that the cells secrete exosomes, tiny vesicles that "contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue," Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he's begun to explore delivering the cardiac stem cells intravenously in a simple infusion -- instead of injecting them directly into the heart, which would be a complex procedure for a human patient -- and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is "very comprehensive."

"Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems," said Gerstenblith, who did not contribute to the new research. "The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly."

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has "led the field in this area."

"The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they've seen in the past," said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells "from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue," Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

"We need to make sure there's no harm being done," Herron said, adding that extending the lifetime and improving quality of life amounts to "a tradeoff between the potential risk and the potential good that can be done."

Capicor hasn't announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven "completely safe" in "over 100 human patients," so it would be possible to fast-track them into the clinic, Marbn explained: "I can't tell you that there are any plans to do that, but it could easily be done from a safety viewpoint."

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Cardiac stem cells rejuvenate rats' aging hearts, study says - CNN - CNN

Cardiac Stem Cells Comments Off on Cardiac stem cells rejuvenate rats’ aging hearts, study says – CNN – CNN | August 14th, 2017

The use of stem cells in the treatment of heart failure cases is currently being investigated. Cardiovascular disease is the #1 killer in the United States accounting forone third ofall deaths.Heart disease kills more people than cancer, HIV, diabetesor trauma. Many advances in medical and surgical treatment of heart disease have contributed to a growing number of patients in their 70s and 80s with congestive heart failure. An estimated 1% of the Western world has congestive heart failure, including over 5 million Americans with an additional 550,000 new cases each year. Patients with advanced heart failure who require hospitalization, have a 50% mortality within the first fiveyears.

The patients with significant coronary artery disease can sometimes undergo coronary artery bypass surgery or percutaneous coronary intervention to open up blocked arteries. In addition, current medical treatment of patients with congestive heart failure include proven beneficial medicine such as beta-blockers, ACE inhibitors, angiotensinIIreceptor blockers, angiotensin IIreceptor blocker Neprilysin inhibitors and diuretics. When appropriate, resynchronization of the right and left ventricles can be accomplished with special types of pacemaker. However, even after following all of these guideline proven therapies, some patients still run out of options and continue to have severe and debilitating congestive heart failure. Heart transplant is a last resort for end stage heart disease.There is a very low number of donor hearts and transplant programs have very restricted eligibility criteria leaving a large number patients with very few options.

An example of a normal LV-gram.

An example of a normal echocardiogram.

There are reasons to believe that regenerative therapy could really help patients with congestive heart failure. Multi-potent cardiac stem cells exist in the heart and participate in the normal turnover of heart muscle cells and small blood vessels.A heart attack kills heart muscle which is made of millions of heart cells. The question is: Would regenerative therapy be able to replace those heart cells or cardiac myocytes?

Thousands of patients have been enrolled in clinical trials to address this question. Regenerative or stem cell therapy has been shown to be safe. Modest benefits have been demonstrated but the mechanism has not been completely elucidated. So far, there is no evidence that cells regenerate from the transplanted stem cells. Animal studies have shown that only 1% of the stem cells injected into the heart tissue are detectable after 1 month. The clinical benefits observed appeared to be due to arelease of growth factors which triggers endogenous repair of the heart cells and inhibits cell death and fibrosis resulting in increased performance of the heart muscle.

An example of an abnormal LV-gram.

An example of an abnormal echocardiogram.

Adult stem cells derived from the bone marrow of healthyyoung donors have been used in clinical trials of heart failure. In the Dream-HF clinical trial, we are using immuno-selected mesenchymalstem cells from healthy adult allogeneic donors. The cells are obtained from their bone marrow, expandedin a manufacturing facility and arecryopreserved until use. These cells are shipped to clinical sites and used for the study.

Allogeneic mesenchymal stem cells have been evaluated in multiple nonclinical and clinical studies, several of which were initiated by Mesoblast, the phase 3 study sponsor. Therapeutic indications under evaluation included heart failure, myocardial infarction, rheumatoid arthritis and graft versus host disease. Currently, results from clinical studies suggest that allogeneic stem cells are generally well tolerated. Moreover,in a phase 2 study ofpatients with heart failure, mesenchymal precursor cell therapy was associated withimprovement inreduction in heart failure hospitalization events and improvementsin functional exercise capacity.

Stem cells from healthy normal volunteers are administered as a 1 time dose of 150 million cells. Myocardial locations are defined within the left ventricle byLeft Ventriculogram (LV-gram)imaging and electromechanical mapping as viable for cell delivery. The cells are administered via a trans-endocardial injection at 15-20 sites inside the heart cavity using a Myostar injection catheter and a NOGA cardiac mapping system. Dr Mendelsohn is the interventional cardiologist performing the injections at BBH Princeton hospital. Only he knows which patients received the stem cells, and he doesnt follow them. The other heart failure specialists follow the patients in the research clinic.

The patients that are injected with stem cells are compared to a group of patient who undergo a Sham or placebo treatment. The treatment arm is not known to the patient or to the heart failure specialist such as myself. This is the only way to find out whether the treatment with stem cells really works. All the patients will be followed by their study team and will be monitored for the clinical effects of stem-cell treatment in patients with congestive heart failure.

No matter how many cases of congestive heart failure we treat, I am still captivated by each and every persons story. One such patient, is a young lady that was treated for heart failure and had a defibrillator placed in 2009. She sought our help and was inquiring about stem cell treatment for her heart. She was only in her early 40s and was desperate to try something new. She was on maximal medical therapy and did not qualify at that time because she was stable. In 2015 however, a clinical deterioration lead to several cardiac procedures including ablation of ventricular arrhythmias and an upgrade of her pacemaker/defibrillator. I thought we were going to lose her. At some point, she was going into incessant ventriculartachycardias and required several prolonged hospitalizations. We referred her to a transplant center and she was evaluated by the transplant team. At the same time, she enrolled in our stem cell research Dream-HF program at the end of 2015.Because she is still part of the research study, I am not sure whether she received stem cells or not. She is amongst one of the many patients that are participating ina stem cell research program that is evaluating cutting edge technology in heart failure. The Dream-HF study is still enrolling patients with chronic systolic heart failure of either ischemic or nonischemic etiology.

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Stem Cells in the Treatment of Heart Failure MyHeart

Cardiac Stem Cells Comments Off on Stem Cells in the Treatment of Heart Failure MyHeart | August 12th, 2017

In the days after a heart attack, surviving patients and their loved ones can breathe a sigh of relief that the immediate danger is over but the scar tissue that forms during the long healing process can inflict lasting damage. Too often it restricts the hearts ability to fill properly between beats, disrupting rhythm and ultimately leading to heart failure. Yet a new possible treatment may help to revitalize an injured ticker.

A cadre of scientists and companies is now trying to prevent or reverse cardiac damage by infusing a cocktail of stem cells into weakened hearts. One company, Melbourne, Australiabased Mesoblast, is already in late-stage clinical trials, treating hundreds of chronic heart failure patients with stem cell precursors drawn from healthy donors hip bones. A randomized trial that includes a placebo group is scheduled to complete enrollment next year.

Mesoblasts earlier-stage trials, published in 2015 inCirculation Research, found that patients who received injections of its cell mixture had no further problems related to heart failure.

Promising results from the new trial would be a major step forward for a field that has long been criticized for studies that are poorly designed, incomplete or lack control-group comparisons, as well as for the peddling of unproved therapies in many clinics worldwide.

Another company, Belgium-based TiGenix, hopes to attack scar tissue before it forms by treating patients with a mixture of heart stem cells within seven days of a heart attack. This approach has just completed phase II trials, but no findings have yet been published.

There are still many unanswered questions about how stem cells typically derived from bones could help heal the heart. Leading theories suggest they may help fight inflammation, revitalize existing heart cells, or drive those cells to divide or promote new blood-vessel growth, says Richard Lee, leader of the cardiovascular program at the Harvard Stem Cell Institute. Other stem cell scientists, including Joshua Hare, who conducted earlier-stage Mesoblast research and directs the Interdisciplinary Stem Cell Institute at the University of Miami, say the cells may work in multiple ways to heal scar tissue. According to Hare, the stem cells could ultimately be a truly regenerative treatment.

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Stem cell therapy for heart failure gets a gold-standard trial - Salon

Cardiac Stem Cells Comments Off on Stem cell therapy for heart failure gets a gold-standard trial – Salon | August 12th, 2017

August 8, 2017 - By Peter Erickson

The stock of Vistagen Therapeutics Incorporated (NASDAQ:VTGN) registered an increase of 11.81% in short interest. VTGNs total short interest was 90,900 shares in August as published by FINRA. Its up 11.81% from 81,300 shares, reported previously. With 28,700 shares average volume, it will take short sellers 3 days to cover their VTGNs short positions. The short interest to Vistagen Therapeutics Incorporateds float is 1.75%.

The stock decreased 2.22% or $0.04 on August 7, reaching $1.76. About shares traded. Vistagen Therapeutics Inc (NASDAQ:VTGN) has declined 50.00% since August 8, 2016 and is downtrending. It has underperformed by 66.70% the S&P500.

VistaGen Therapeutics, Inc. is a clinical-stage biopharmaceutical company. The company has market cap of $16.74 million. The Firm is engaged in developing and commercializing product candidates for patients with diseases and disorders involving the central nervous system . It currently has negative earnings. The Companys lead product candidate, AV-101, is an orally available prodrug candidate in Phase II development, initially for the adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressants approved by the United States Food and Drug Administration (FDA).

More notable recent Vistagen Therapeutics Inc (NASDAQ:VTGN) news were published by: Prnewswire.com which released: VistaGen Therapeutics Reports Second Quarter 2017 Financial Results and on November 14, 2016, also Finance.Yahoo.com with their article: VistaGen Therapeutics Receives European Patent Office Notice of Intention to published on March 29, 2017, Prnewswire.com published: VistaGen Therapeutics Grants Exclusive Sublicense of Cardiac Stem Cell on December 14, 2016. More interesting news about Vistagen Therapeutics Inc (NASDAQ:VTGN) were released by: Prnewswire.com and their article: VistaGen Therapeutics to Present at Biotech Showcase 2017 published on January 05, 2017 as well as Prnewswire.coms news article titled: VistaGen Therapeutics Provides Business Outlook and Sets Corporate Milestones with publication date: September 22, 2016.

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What's Propelling Vistagen Therapeutics Incorporated (NASDAQ:VTGN) After Higher Shorts Reported? - BZ Weekly

Cardiac Stem Cells Comments Off on What’s Propelling Vistagen Therapeutics Incorporated (NASDAQ:VTGN) After Higher Shorts Reported? – BZ Weekly | August 11th, 2017

SOUTH SAN FRANCISCO, CA--(Marketwired - August 08, 2017) - VistaGen Therapeutics Inc. (NASDAQ: VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, announced today that the Company has received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for U.S. Patent Application No. 14/359,517 regarding proprietary methods for producing hematopoietic precursor stem cells, which are stem cells that give rise to all of the blood cells and most of the bone marrow cells in the body, with potential to impact both direct and supportive therapy for autoimmune disorders and cancer.

The breakthrough technology covered by the allowed U.S. patent was discovered and developed by distinguished stem cell researcher, Dr. Gordon Keller, Director of the UHN's McEwen Centre for Regenerative Medicine in Toronto, one of the world's leading centers for stem cell and regenerative medicine research and part of the University Health Network (UHN), Canada's largest research hospital. Dr. Keller is a co-founder of VistaGen and a member of the Company's Scientific Advisory Board. VistaGen holds an exclusive worldwide license from UHN to the stem cell technology covered by the allowed U.S. patent.

"We are pleased to report that the USPTO has allowed another important U.S. patent relating to our stem cell technology platform, stated Shawn Singh, Chief Executive Officer of VistaGen. "Because the technology under this allowed patent involves the stem cells from which all blood cells are derived, it has the potential to reach the lives of millions battling a broad range of life-threatening medical conditions, including cancer, with CAR-T cell applications and foundational technology we believe ultimately will provide approaches for producing bone marrow stem cells for bone marrow transfusions. As we continue to expand the patent portfolio of VistaStem Therapeutics, our stem cell technology-focused subsidiary, we enhance our potential opportunities for additional regenerative medicine transactions similar to our December 2016 sublicense of cardiac stem cell technology to BlueRock Therapeutics, while focusing VistaStem's internal efforts on using stem cell technology for cost-efficient small molecule drug rescue to expand our drug development pipeline."

About VistaGenVistaGen Therapeutics, Inc. (NASDAQ: VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. VistaGen's lead CNS product candidate, AV-101, is in Phase 2 development, initially as a new generation oral antidepressant drug candidate for major depressive disorder (MDD). AV-101's mechanism of action is fundamentally different from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a small Phase 2 monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 180-patient Phase 2 study of AV-101 as an adjunctive treatment for MDD patients with an inadequate response to standard, FDA-approved antidepressants. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Company's Phase 2 adjunctive treatment study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including neuropathic pain, epilepsy, Huntington's disease, and levodopa-induced dyskinesia associated with Parkinson's disease and other disorders where modulation of the NMDA receptors, activation of AMPA pathways and/or key active metabolites of AV-101 may achieve therapeutic benefit.

About VistaStemVistaStem Therapeutics is VistaGen's wholly-owned subsidiary focused on applying human pluripotent stem cell (hPSC) technology, internally and with third-party collaborators, to discover, rescue, develop and commercialize (i) proprietary new chemical entities (NCEs), including small molecule NCEs with regenerative potential, for CNS and other diseases and (ii) cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. VistaStem's internal drug rescue programs are designed to utilize CardioSafe 3D, its customized cardiac bioassay system, to develop small molecule NCEs for VistaGen's pipeline. To advance potential regenerative medicine (RM) applications of its cardiac stem cell technology, in December 2016, VistaStem exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established in 2016 by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac cells for the treatment of heart disease. In a manner similar to its exclusive sublicense agreement with BlueRock Therapeutics, VistaStem may pursue additional collaborations and potential RM applications of its stem cell technology platform, including using blood, cartilage, and/or liver cells derived from hPSCs, for (i) cell-based therapy, (ii) cell repair therapy, and/or (iii) tissue engineering.

For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking StatementsThe statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2 (monotherapy) and/or the Company's planned Phase 2 (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, including neuropathic pain and L-DOPA-induced dyskinesia associated with Parkinson's disease, the potential for the Company's stem cell technology to produce NCEs, cellular therapies, regenerative medicine or bone marrow stem cells to treat any medical condition, including autoimmune disorders and cancer, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the AV-101 clinical development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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VistaGen Receives Notice of Allowance from US Patent and Trademark Office for US Patent regarding Breakthrough ... - Marketwired (press release)

Cardiac Stem Cells Comments Off on VistaGen Receives Notice of Allowance from US Patent and Trademark Office for US Patent regarding Breakthrough … – Marketwired (press release) | August 10th, 2017

GREENVILLE Onboard the next SpaceX cargo spacecraft launching to the International Space Station (ISS) from Pad 39A at the Kennedy Space Center will be a commercial research system owned and operated by Techshot Inc. The equipment will conduct regenerative medicine experiments onboard the station before returning to Earth in the same capsule for a splashdown off the coast of Southern California approximately 30 days later.

Techshots ADvanced Space Experiment Processor (ADSEP) is a device approximately the size of a microwave oven that contains three separate modules, each of which simultaneously can process experiments in three separate on-orbit replaceable automated mini-laboratory cassettes. Two of the three cassettes on the mission will conduct research for a team led by Robert Schwartz, Ph.D., from the University of Houston.

Funded by the Center for the Advancement of Science in Space (CASIS), the study will evaluate a new approach to growing human tissue for transplant. The microgravity environment onboard the ISS could improve cell growth and development and 3D tissue formation, enabling discoveries that will advance translational disease treatments. Previous studies on Earth by Schwartz and his collaborators at the Texas Heart Institute and the Baylor College of Medicine have found that low gravity environments help specially programmed stem cells move toward becoming new heart muscle cells, which may be used to repair damaged hearts on Earth.

The third cassette contains an experiment conducted by and for Techshot itself. The company is developing a 3D bioprinter for the ISS known as the Techshot BioFabrication Facility (BFF), which it expects to launch to the station near the end of 2018. Critical to the success of the printer will be the ability to provide nutrients and mechanical stress for organs and tissues it manufactures in space strengthening them and keeping them viable for transplantation back on Earth.

Approximately 36 hours prior to launch, Techshot scientists in a laboratory at the Kennedy Space Center will 3D print a one centimeter thick construct consisting of stem cells and heart muscle cells. Theyll then place it inside the prototype BFF cell culturing subsystem, which for this mission is temporarily housed inside an ADSEP cassette. The printer used in the lab will be the same modified nScrypt unit that was the first to 3D print cardiac constructs with adult human stem cells in microgravity aboard an aircraft in parabolic flight. Video captured inside the cassette during the month-long experiment, and the tissue itself which is expected to have developed its own micro blood vessels will be evaluated for effectiveness after return from space.

Techshots space bioprinting program leverages its terrestrially based technologies for cell isolation and vascular graft development, and its decades long experience culturing cells in space, said Techshot Chief Scientist Eugene Boland, Ph.D., in a news release. Being able to test our novel approach for culturing 3D printed cells more than a year before we fly the whole BFF is invaluable. The data from this mission will get us one step closer toward our goal of helping eliminate organ shortages.

Founded in 1988, Techshot Inc., develops technologies used in the aerospace, defense and medical industries. Through its Space Act Agreement with NASA, and its role as an official CASIS Implementation Partner, the company provides equipment and services that help federal, institutional and industrial customers live and work in space. http://www.Techshot.space

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Techshot system headed to space | News | newsandtribune.com - Evening News and Tribune

Cardiac Stem Cells Comments Off on Techshot system headed to space | News | newsandtribune.com – Evening News and Tribune | August 10th, 2017

For patients with severe and end-stage heart failure there are few treatment options left apart from transplants and stem-cell therapy. But a new Israeli study finds that stem-cell therapy may harm heart-disease patients.

The research, led by Prof. Jonathan Leor of Tel Aviv Universitys Sackler Faculty of Medicineand Sheba Medical Center and conducted by TAUs Dr. Nili Naftali-Shani, explores the current practice of using cells from the host patient to repair tissue and contends that this can prove toxic for patients.

We found that, contrary to popular belief, tissue stem cells derived from sick hearts do not contribute to heart healing after injury, said Leor. Furthermore, we found that these cells are affected by the inflammatory environment and develop inflammatory properties. The affected stem cells may even exacerbate damage to the already diseased heart muscle.

Tissue or adult stem cells blank cells that can act as a repair kit for the body by replacing damaged tissue encourage the regeneration of blood vessel cells and new heart muscle tissue. Faced with a worse survival rate than many cancers, many heart-failure patients have turned to stem-cell therapy as a last resort.

But our findings suggest that stem cells, like any drug, can have adverse effects, said Leor. We concluded that stem cells used in cardiac therapy should be drawn from healthy donors or be better genetically engineered for the patient.

The researchers, who published their study in the journal Circulation, also discovered the molecular pathway involved in the negative interaction between stem cells and the immune system as they isolated stem cells in mouse models of heart disease. Afterward, they focused on cardiac stem cells in patients with heart disease.

The results could help improve the use of autologous stem cells those drawn from the patients themselves in cardiac therapy, Leor said.

We showed that the deletion of the gene responsible for this pathway can restore the original therapeutic function of the cells, said Leor. Our findings determine the potential negative effects of inflammation on stem-cell function as theyre currently used. The use of autologous stem cells from patients with heart disease should be modified. Only stem cells from healthy donors or genetically engineered cells should be used in treating cardiac conditions.

The researchers are currently testing a gene editing technique (CRISPER) to inhibit the gene responsible for the negative inflammatory properties of the cardiac stem cells of heart disease patients. We hope our engineered stem cells will be resistant to the negative effects of the immune system, said Leor.

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Stem-cell treatment may harm heart disease patients - ISRAEL21c

Cardiac Stem Cells Comments Off on Stem-cell treatment may harm heart disease patients – ISRAEL21c | August 9th, 2017

Earlier this year, Texas Heart Institute received Alpha Phi Foundations 2017 Heart to Heart Grant. The $100,000 grant will fund research led by Doris Taylor, Ph.D., director of the Regenerative Medicine Research and the Center for Cell and Organ Biotechnology at the Texas Heart Institute, to study cardiac repair in women at the cellular level.

Were just really passionate about these projects that have long-term clinical relevancy, as a women-driven organization and being committed to womens heart health, said Colleen Sirhal, vice chair of the Alpha Phi Foundation.

The study will explore sex differences in blood, bone marrow and stem cells of patients enrolled in cell therapy clinical trials.

While bone marrow cell therapy has been used to treat cardiovascular disease in clinical trials, very few studies have been conducted to assess the sex differences in efficacy and outcomes. By performing a proteomic analysis of the samples and evaluating the proteins that cells produce and secrete, the results could shed light on unanswered questions related to critical sex-specific differences in cardiovascular disease, potentially leading to improved cell therapies.

Its about time that were paying attention to sex differences, Taylor said. Were not just small men. The biology is different.

Heart disease remains the No. 1 cause of death in both men and women in the United States, yet theres a limited understanding in the scientific community as to why it affects men and women differently. For example, women 45 years old and younger have a higher likelihood than men of dying within a year of their initial heart attack.

In addition, women have a higher risk of developing small vessel disease, in which the walls of tiny vessels within the heart muscle become blocked rather than larger arteries, causing heart-related chest pain. Because the major coronary arteries may look normal, women with small vessel disease can have a heart attack go undiagnosed and untreated.

We know heart disease happens differently in men and women, Taylor said. More young women than men die of heart disease. Why is that? Is there something that happens early? If we only look at these women who are older, are we missing something major? By looking at healthy, normal younger women, were going to be able to do comparisons across time, comparisons by disease, and comparisons by sex. I think thats really exciting.

Historically, women and minorities have largely been underrepresented in research and clinical trials, especially pertaining to cardiovascular disease.

Dr. Taylors colleague at the Texas Heart Institute, Stephanie Coulter, M.D., a cardiologist and the director of the Center for Womens Heart and Vascular Health at Texas Heart Institute and a recipient of the 2013 Heart to Heart Grant, is actively recruiting younger women to participate in her research registry.

Since women are typically affected by heart disease a decade or more later than men, age may also have played a role in this underrepresentation, Coulter said. Our Womens Center research is focusing on women age 18 and older to address this very issue.

Coulter added that trials focusing on prevention in women, such as the Womens Health Initiative and Womens Health Study, have, in fact, had clinical impact. However, the percentage of women enrolling in clinical trials continues to be disproportionate to the prevalence of cardiovascular disease in women, but we are seeing improvements thanks to multiple initiatives in the U.S. that continue to address the issue of women in clinical trials.

Its easy for people to assume that if you study men, itll apply to women, but it seems anathema to people to assume that if you study women it might benefit men, Taylor said. At the end of the day, when it comes time to look at the data and ask, How does this treatment work in women? How does this treatment work in men?, oftentimes there arent enough women enrolled in the trials to split that out. Statistically, youd be doing yourself a disservice.

Taylor has spent nearly two decades studying key contributors to cardiac repair at the cellular level, specifically looking at proteins cells produce and secrete based on gender as a new frontier in cell therapy.

Early on in Taylors career, she studied how bone marrow cells behaved based on gender. She extracted cells from male mice and administered them to female mice and vice versa, allowing her to track the Y chromosome. The results showed that only the males treated with female cells improved. This phenomenon raised the question of whether or not the bone marrow cells were the same.

After measuring the bone marrow cells that were present in males and females, Taylor discovered that the cells were inherently different: In the male mice, there were more inflammatory cells, fewer progenitor and stem cells and a different number of immune cells than in the female mice. In addition, when the bone marrow cells were placed in a petri dish, the female cells produced more growth factors responsible for recruiting repair cells after an injury.

Taylor conducted follow-up experiments in which she gave female and male cells to both female and male mice. The results confirmed her hunch: The only cells that were reparative were the female cells.

It made me realize a critical detail for the first time:Every time we take bone marrow from a different person with the intention of delivering it back to them as a therapy, if we look at the cells present in the marrow, theyd be different, Taylor said. Which means, every time were doing an autologous cell therapytrial, in which you take bone marrow and deliver it back to an individual, you are giving each person a completely different or unique drug in that trial.

Through the Heart to Heart grant, the data from Taylors research will allow her to build upon her early research on sex differences and, hopefully, identify a way to optimize cell therapy.

Already cells are as good as some drugs. If we optimize them and choose the right cells for the right patient at the right time, maybe well hit the home run, Taylor said.

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Texas Heart Institute Awarded Grant to Study Sex Differences in Cardiac Repair - Texas Medical Center (press release)

Cardiac Stem Cells Comments Off on Texas Heart Institute Awarded Grant to Study Sex Differences in Cardiac Repair – Texas Medical Center (press release) | August 9th, 2017

Current debate about the future of the Victorian Heart Hospital, which when completed will be Australia's first cardiac hospital,focuses on issues such as cost and contracts. And, in these tight economic times, it is right to ask these questions.

However, Australia's first dedicated specialist heart hospital will be so much more. Thehospital will be in the same league as some of the great cardiac hospitals, such as the Barts Heart Centre in London and the Montreal Heart Institute in Canada.

More Victorians, men and women, die from heart disease than any other cause. People are living longer long enough to have, and survive, heart attacksthat may become heart disease and heart failure further down the line.

In the catchment area that will feed into the Victorian Heart Hospital the population projections for people at risk of heart disease are even worse. Aboutone-quarter (or eight out of 31) of the metropolitan local government areas with above average heart attack rates fall into the catchment area of the new hospital. This is an area whose population needs a facility like this.

But the hospitalwill be so much more than a hospital for patients with cardiovascular disease and events. Much has been said about the dedicated areas for Monash University and Monash Health researchers devoted to cardiac research.

Having the researchers sitting in the midst of the clinicians and patients, and in many cases being situated within the hospital means the problems the scientists address are the ones that are identified by those at the coalface, the clinicians and health professionals.

One of the hospital'score research areas, for example, will be stem cell research. We have recruited some of the best stem cell scientists in the world. They will work with Monash University's Australian Regenerative Medicine Institute and heart hospital clinicians to develop cellular patches that can be created from a patient's own cells to replace the areas of the heart left dead by a heart attack. This damaged tissue, currently cannot be fixed, and often leads to heart failure, so the need for this sort of research is paramount.

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Monash Health has an outstanding international reputation for attracting clinical trials into new heart procedure techniques, with more than 30 trials currently being conducted. As an example, the international medical device makerMedtronicchose Monash Heart cardiologists to conduct the first trial of a new way to replace mitral valves in the hearts of patients whose health would not withstand traditional open-heart surgery. These trial patients have had their life saved by this device.

This is translational research at its best taking new discoveries and therapies and making sure they are safe in patients. These innovations then become, as fast as possible, treatments we can offer all Victorians. It is no surprise that many of Australia's largest medical device manufacturers and innovators are situated around Monash University and benefit from the strong biomedical focus the university offers.

Co-location of the Victorian Heart Hospital at the Monash University campus will strengthen the nexus between industry, biomedical research and clinical care, including clinical trials that will result in Victorians benefiting from the best advances in cardiac care.

The Victorian Heart Hospitalis a way for Victoria to future-proof its citizens against heart disease for the next five decades. It will be where we develop new technologies, devices and treatments that can be used to deal with the patients that come throughour doors.

There will be more non-surgical alternatives and prevention strategies developed and offered. We will provide a health and wellness department that assists patients in dealing with the depression that can follow cardiac surgery, as well as assisting patients in techniques that can help them lower their risk of further cardiac events.

The hospitalwill not only put Victoria on the world map, it will be a groundbreaking commitment to the health of Victorians.

Sarah Newton is deputy dean, external relations, Monash University's faculty of medicine, nursing and health sciences.

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Funding debate aside, this is why we need a new heart hospital - The Sydney Morning Herald

Cardiac Stem Cells Comments Off on Funding debate aside, this is why we need a new heart hospital – The Sydney Morning Herald | August 7th, 2017

One week ago, MIT Technology Review reported that scientists at an Oregon-based lab had modified the DNA of human embryos using the gene-editing technique known as CRISPR. That was a first for the United States; until then, such a procedure had only ever been done in China.

The researchers, led by Shoukhrat Mitalipov from Oregon Health and Science University, had altered the gene behind an unspecified inherited disease in a number of one-cell embryos. These embryos werent allowed to develop for more than a few days, and there was never any intention to implant them into a womb. The story fueled another cycle of discussion about designer babies, and fears that a Gattaca-style world was just around the corner.

But the full details of the experiment, which are released today, show that the study is scientifically important but much less of a social inflection point than has been suggested. This has been widely reported as the dawn of the era of the designer baby, making it probably the fifth or sixth time people have reported that dawn, says Alta Charo, an expert on law and bioethics at the University of Wisconsin-Madison. And its not.

Given the persistent confusion around CRISPR and its implications, I've laid out exactly what the team did, and what it means.

Who did the experiments?

Shoukhrat Mitalipov is a Kazakhstani-born cell biologist with a history of breakthroughsand controversyin the stem cell field. He was the scientist to clone monkeys. He was the first to create human embryos by cloning adult cellsa move that could provide patients with an easy supply of personalized stem cells. He also pioneered a technique for creating embryos with genetic material from three biological parents, as a way of preventing a group of debilitating inherited diseases.

Although MIT Tech Review name-checked Mitalipov alone, the paper splits credit for the research between five collaborating teamsfour based in the United States, and one in South Korea.

What did they actually do?

The project effectively began with an elevator conversation between Mitalipov and his colleague Sanjiv Kaul. Mitalipov explained that he wanted to use CRISPR to correct a disease-causing gene in human embryos, and was trying to figure out which disease to focus on. Kaul, a cardiologist, told him about hypertrophic cardiomyopathy (HCM)an inherited heart disease thats commonly caused by mutations in a gene called MYBPC3. HCM is surprisingly common, affecting 1 in 500 adults. Many of them lead normal lives, but in some, the walls of their hearts can thicken and suddenly fail. For that reason, HCM is the commonest cause of sudden death in athletes. There really is no treatment, says Kaul. A number of drugs are being evaluated but they are all experimental, and they merely treat the symptoms. The team wanted to prevent HCM entirely by removing the underlying mutation.

They collected sperm from a man with HCM and used CRISPR to change his mutant gene into its normal healthy version, while simultaneously using the sperm to fertilize eggs that had been donated by female volunteers. In this way, they created embryos that were completely free of the mutation. The procedure was effective, and avoided some of the critical problems that have plagued past attempts to use CRISPR in human embryos.

Wait, other human embryos have been edited before?

There have been three attempts in China. The first twoin 2015 and 2016used non-viable embryos that could never have resulted in a live birth. The thirdannounced this Marchwas the first to use viable embryos that could theoretically have been implanted in a womb. All of these studies showed that CRISPR gene-editing, for all its hype, is still in its infancy.

The editing was imprecise. CRISPR is heralded for its precision, allowing scientists to edit particular genes of choice. But in practice, some of the Chinese researchers found worrying levels of off-target mutations, where CRISPR mistakenly cut other parts of the genome.

The editing was inefficient. The first Chinese team only managed to successfully edit a disease gene in 4 out of 86 embryos, and the second team fared even worse.

The editing was incomplete. Even in the successful cases, each embryo had a mix of modified and unmodified cells. This pattern, known as mosaicism, poses serious safety problems if gene-editing were ever to be used in practice. Doctors could end up implanting women with embryos that they thought were free of a disease-causing mutation, but were only partially free. The resulting person would still have many tissues and organs that carry those mutations, and might go on to develop symptoms.

What did the American team do differently?

The Chinese teams all used CRISPR to edit embryos at early stages of their development. By contrast, the Oregon researchers delivered the CRISPR components at the earliest possible pointminutes before fertilization. That neatly avoids the problem of mosaicism by ensuring that an embryo is edited from the very moment it is created. The team did this with 54 embryos and successfully edited the mutant MYBPC3 gene in 72 percent of them. In the other 28 percent, the editing didnt worka high failure rate, but far lower than in previous attempts. Better still, the team found no evidence of off-target mutations.

This is a big deal. Many scientists assumed that theyd have to do something more convoluted to avoid mosaicism. Theyd have to collect a patients cells, which theyd revert into stem cells, which theyd use to make sperm or eggs, which theyd edit using CRISPR. Thats a lot of extra steps, with more risks, says Alta Charo. If its possible to edit the embryo itself, thats a real advance. Perhaps for that reason, this is the first study to edit human embryos that was published in a top-tier scientific journalNature, which rejected some of the earlier Chinese papers.

Is this kind of research even legal?

Yes. In Western Europe, 15 countries out of 22 ban any attempts to change the human germ linea term referring to sperm, eggs, and other cells that can transmit genetic information to future generations. No such stance exists in the United States but the Food and Drug Administration will not fund research that makes such modifications. Separately, federal agencies like the National Institutes of Health are banned from funding research that ultimately destroys human embryos. But the Oregon team used non-federal money from their institutions, and donations from several small non-profits. No taxpayer money went into their work.

Why would you want to edit embryos at all?

Partly to learn more about ourselves. By using CRISPR to manipulate the genes of embryos, scientists can learn more about the earliest stages of human development, and about problems like infertility and miscarriages. Thats why biologist Kathy Niakan from the Crick Institute in London recently secured a license from a British regulator to use CRISPR on human embryos.

The Oregon team has more immediate goals in mind. Through their work, they hope to eventually give people with HCM the certainty that they would not pass on their condition to their children. If we had the freedom to do this, we could theoretically remove HCM in a generation, says Kaul. Thats the potential and we have to let the potential and reality meet someday.

In February, an expert committee convened by the U.S. National Academy of Sciences (and chaired by Charo) offered qualified support for germ-line editing. In a report, they said that such editing shouldnt be used to enhance healthy people, but could be permitted to treat or prevent disease and disability, provided certain criteria were met. The technique would need to become much safer and more efficient, and a stringent oversight system should be set in place. It should be an option of last resort for couples who have a serious genetic disease and have no other way of producing a healthy child. But remember that the Oregon team havent done anything even close to this yet. They just edited embryos for basic research purposesa use that the NAS report wholeheartedly endorsed.

How do people with HCM feel about this?

I reached out to an advocacy organization that raises awareness of HCM, but havent heard back. But John Jefferies, a cardiologist at Cincinnati Children's Hospital Medical Center, says, I think those caring for these patients would greatly welcome this move. The medical therapies we have for this disease are limited and do not reverse the cardiac [problems]. This offers a potential cure for the disease by avoiding it.

Arent there already other ways of doing that?

Yes, and therein lies the debate. A couple could opt for preimplantation genetic diagnosis (PGD), where their sperm and eggs are introduced in a lab, and the resulting embryos are genetically screened to find those that are free of disease genes. This technique already works well, so why bother with gene-editing at all? If one of the wannabe parents has a copy of an HCM-causing mutation, then half of the resulting embryos will carry that mutationand be discarded. But if Oregon team gets their technique working perfectly, then every embryo could be potentially implanted. Theyre not trying to supplant PGD. Theyre trying to bolster it.

But these days with IVF, the tendency is to put in one embryo at a time to avoid having twins or triplets, says Charo. If it doesnt work after a few times, youre less likely to succeed. So its not clear to me how relevant this is for preventing genetic disease. Mitalipov disagrees. IVF is not efficient and with this procedure, we hope patients will be able to become pregnant on just one cycle, he says. He also he sees this as a moral issue. You have no right to throw away 50 percent of these embryos when you can correct them. Its very 19th-century. Some people say that our work is ethically wrong but I think it is ethically right.

Does the editing approach have limitations?

Yes, and they are important ones. CRISPR works by cutting DNA at a precise point. A cell then uses a matching piece of DNA as a template for repairing the cut. Its like tearing a misprinted page from a book and using a pristine edition to fill out the missing text. Mitalipovs team offered the embryos a pristine copy of the MYBPC3 gene to be used in the repair process. But to their surprise, the embryos largely ignored this gift. Instead, they used the healthy copy of the gene from the egg to repair the CRISPR-sliced mutant version from the sperm. That means that this technique would not work if both parents have HCM. If both pass a mutant version of MYBPC3 to an embryo, theres no healthy copy to use as a template. We still need to figure out how to correct those, says Mitalipov.

When can we expect such editing to be commonplace?

Not for a while. The technique would need to be refined, tested on non-human primates, and shown to be safe. The safety studies would likely take 10 to 15 years before FDA or other regulators would even consider allowing clinical trials, wrote bioethicist Hank Greely in a piece for Scientific American. The Mitalipov research could mean that moment is 9 years and 10 months away instead of 10 years, but it is not close. In the meantime, Kaul says, Well get the method to perfection so that when its possible to use it in a clinical trial, we can.

Isnt this a slippery slope toward making designer babies?

In terms of avoiding genetic diseases, its not conceptually different from PGD, which is already widely used. The bigger worry is that gene-editing could be used to make people stronger, smarter, or taller, paving the way for a new eugenics, and widening the already substantial gaps between the wealthy and poor. But many geneticists believe that such a future is fundamentally unlikely because complex traits like height and intelligence are the work of hundreds or thousands of genes, each of which have a tiny effect. The prospect of editing them all is implausible. And since genes are so thoroughly interconnected, it may be impossible to edit one particular trait without also affecting many others.

Theres the worry that this could be used for enhancement, so society has to draw a line, says Mitalipov. But this is pretty complex technology and it wouldnt be hard to regulate it.

Wait, havent I read about DIY gene-editors, who are using CRISPR in their basement labs?

Yes, but none of those people are using the technique to edit human embryos. Mitalipovs work is essentially a form of IVF. Its not simple IVF either, he says. Everything needs to be done exactly the way we did it. Youd need to do a biopsy with every embryo to screen for off-target mutations. You cant do it at home.

So, this isnt the start of Gattaca?

I doubt it.

Brave New World?

Unlikely.

Does this discovery have any social importance at all?

Its not so much about designer babies as it is about geographical location, says Charo. Its happening in the United States, and everything here around embryo research has high sensitivity. She and others worry that the early report about the study, before the actual details were available for scrutiny, could lead to unnecessary panic. Panic reactions often lead to panic-driven policy ... which is usually bad policy, wrote Greeley.

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The Designer Baby Era Is Not Upon Us - The Atlantic

Cardiac Stem Cells Comments Off on The Designer Baby Era Is Not Upon Us – The Atlantic | August 2nd, 2017

Though the jury is out on whether we should try to modify the genes of human embryos, that hasnt stopped researchers from finessing the widely lauded CRISPR gene-editing technique. So far three attempts by Chinese researchers have made the pitfalls clear: the technique introduces more errors than it fixes. It also produces mosaic embryos where some cells get fixed, others dont.

Now, as reported in Nature, an international team led by Shoukhrat Mitalipov at Oregon Health and Science University has found a way to move past these pitfalls. Its a staggering result, says geneticist Leanne Dibbens, at the University of South Australia. This is what weve all been looking for.

Shoukrat Mitalipov.

Dieter Egli, NYSCF

Mitalipov and his colleagues have convincingly repaired embryos carrying the faulty gene, cardiac myosin-binding protein C (MYBPC3). The defective gene causes hypertrophic cardiomyopathy, the most common cause of sudden cardiac arrest in young athletes. The condition affects one in 500 people. By using this technique, its possible to reduce the burden of this heritable disease on the family and eventually the human population, Mitalipov says. Every generation on would carry this repair because weve removed the disease-causing gene variant from that familys lineage.

Three previous attempts to edit the genes of human embryos by labs in China all showed problems with mosaicism and mistakes, so-called off-target effects. The first two of those studies used defective IVF embryos that could never develop into a baby (they had been inadvertently fertilised with two sperm) as a way to sidestep the ethical minefield.

The first study, published in 2015, attempted to repair a defective gene causing the blood disease beta thalassemia. The second study, published in 2016, edited a gene to confer HIV resistance to the embryo. The third, published in March this year, edited genes associated with the diseases beta thalassemia and favism. This time the researchers used normal embryos, which they found increased the proportion of embryos that were edited from 14% to 50%. Nevertheless the embryos still showed evidence of off-target effects and mosaicism.

The Mitalipov-led team is the first to demonstrate error-free editing of human embryos. They seem to have a knack when it comes to manipulating embryos. Mitalipov also carries the distinction of being the first to crack the long-standing problem of cloning human embryos and deriving embryonic stem cells.

The key to the current success appears to come down to when the CRISPR editor is introduced to the embryo. Past attempts introduced CRISPR once the embryo had already been fertilised; in the current report, CRISPR was added to eggs at an earlier stage, at the same time as the sperm.

The sperm came from a donor with hypertrophic cardiomyopathy. Like all those affected, he carried both a normal and a defective copy of the MYBPC3 gene so his sperm population was a 50:50 mix of normal and defective. That meant half the fertilised embryos would be normal; half defective.

The researchers co-injected the affected donors sperm together with the CRISPR editor. They then analysed the embryos after they had undergone two or three divisions. Out of 58 embryos, 42 showed the normal gene in every cell. This means the technique successfully increased the number of healthy embryos from 50% to 70%.

Researchers at collaborating labs in South Korea and China also carried out thorough checks of the embryos DNA to see if there had been mistakes elsewhere. Remarkably, no off-target effects were detected.

Another remarkable finding was the way the repairs to the embryos faulty DNA took place. Normally the CRISPR editor is added together with a snippet of DNA carrying the correct DNA code. It uses this as a template to make the corrections rather like checking a dictionary when you correct the spelling of word. The surprise was that instead of checking the foreign DNA to make the corrections, the embryo checked the mothers copy of the MYBPC3 gene. The preferential use of the mothers own template may have something to do with using very early stage embryos. It may also explain why the editing was so accurate. Says co-author Jun Wu of the Salk Institute in San Diego: Our technology successfully repairs the disease-causing gene mutation by taking advantage of a DNA repair response unique to early embryos.

The authors believe their success at avoiding mosaicism also lies in editing early embryos. By co-delivering the CRISPR editor with sperm, there was time for the embryo to carry out its repairs well before it began dividing, avoiding the possibility of cells splitting before receiving a corrected copy of the DNA.

Not all the embryos were perfectly fixed, though: 16 showed erroneous fixes to their MYBPC3 gene.

However, the authors say that, by increasing the number of healthy embryos from 50% to 70%, their work could provide couples with a larger number of healthy embryos, improving the chance of successful IVF. According to another co-author, Paula Amato, professor of obstetrics and gynaecology in OHSUs School of Medicine: If proven safe, this technique could potentially decrease the number of cycles needed for people trying to have children free of genetic disease.

Clearly there is still work to do and debates still to be resolved. As Dibbens puts it: The study advances our understanding of gene editing technologies and again highlights the need for discussions on what situations gene editing will be used in in the future.

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Error-free editing of human embryos achieved by US researchers - Cosmos

Cardiac Stem Cells Comments Off on Error-free editing of human embryos achieved by US researchers – Cosmos | August 2nd, 2017

Cellular Dynamics International, the stem cell company founded by UW-Madison stem cell pioneer James Thomson, is backing off on moving its headquarters to a big, new building in Verona and will stay in Madison, at least for now, as it prepares to push forward with its first potential stem cell-based treatment in early 2018.

CDI president Kaz Hirao said Thursday the company is shelving plans to shift operations to a $40 million, 133,700-square-foot building that was to be built for CDI on Kettle Moraine Trail in Verona. The building was expected to house 280 employees, with so-called clean rooms, quality-control labs, processing rooms and offices.

Instead, CDIs main offices and labs will remain at 525 Science Drive in University Research Park and the company will remodel an existing building whose site has not yet been determined to house several clean rooms that will meet government standards for manufacturing stem cells for use in clinical drug trials.

Fujifilm (CDIs parent company) has a very strong commitment and wants to see (the) Madison (site) grow in the future. Strategy-wise, that has not changed, Hirao said. Madison has a great ecosystem for our businesses.

He said the National Eye Institute plans to submit an application to the U.S. Food and Drug Administration in January 2018 for a retinal cell therapy it has been developing with CDI for age-related macular degeneration, an eye disease that can lead to blindness. The National Eye Institute has conducted animal studies on the drug, Hirao said.

It is the first of a series of stem cell-based drugs the company is working on. CDI expects to file investigational new drug applications for treating Parkinsons disease and for cardiac disease in 2019, he said.

In order to make stem cells that meet government standards for use in human clinical trials, Hirao said the company will establish clean rooms that meet regulations for current good manufacturing practices. He said he expects to designate a location in the next month or two, within about a 15-minute drive of CDI headquarters, to handle the companys stem cell manufacturing needs for the immediate future.

Next year, CDI will review its plans again, Hirao said, and will again consider a move to a larger, consolidated building. If it decides to go ahead with that, Verona would be one of the preferred options, he said.

CDI had obtained up to $6 million in financial incentives from the city of Verona for the building that was to be built and owned by developer John K. Livesey.

Verona planning and development director Adam Sayre called CDIs decision to pull back on the plans unfortunate, but said city officials will keep in contact with Cellular Dynamics over the coming months.

The city would continue to welcome them with open arms, Sayre said. Well see what the next year brings.

At University Research Park, CDI occupies about 55,000 square feet, director Aaron Olver said. Weve recently provided CDI with some additional space to help them grow, he said.

CDI is one of the true gems among companies powered by UW-Madison research, and we would certainly do anything we could to help them find clean room space to continue their work, Olver said.

Founded in 2004, CDI was acquired by Fujifilm Holdings Corp. for $307 million in April 2015.

The company has 165 employees, including about 125 in Madison. Hirao said he expects to add employees, but said its too soon to estimate how many, or how quickly the company will grow.

Original post:
CDI ditches move to Verona - Madison.com

Cardiac Stem Cells Comments Off on CDI ditches move to Verona – Madison.com | July 31st, 2017

Advances in medical imaging enable bespoke tissues and organs to be developed for transplant or engraftment with remarkable resolution and definition using 3D bioprinting. The incorporation of stem cell therapies into these 3D tissue constructs is incredibly promising for the delivery of pioneering stem cell regenerative therapies. Typically, 3D bioprinting requires use of a biomaterial to aid with deposition, which can cause negative host responses. To avoid such problems, US researchers have developed a biomaterial-free cardiac patch (Scientific Reports 7 4566).

Heart disease affects thousands of people every year and effective repair of cardiac tissue would reduce a large medical health care burden. Researchers from the Narutoshi Hibino lab at Johns Hopkins Hospital and Johns Hopkins University have devised a 3D-bioprinting procedure that allows for the biofabrication of cardiac tissue patches to deliver regenerative stem cells, without using biomaterials. The process utilises aggregated balls of cardiac cells (cardiospheroids), which are directly printed into a cardiac patch construct. The cardiospheroids are identified, picked up by a vacuum and bioprinted directly onto a needle microarray (a video of the 3D-bioprinting process used is available from JOVE). This novel method allows the patch to be constructed with cells alone and will avoid detrimental effects induced by biomaterial grafts.

Stem cell techniques for tissue regeneration typically rely on biomaterial scaffolds to provide structure and support for cells during grafting. The grafting or introduction of biomaterials to a patient induces an immune response, or can create scar tissue from the graft, potentially damaging the region of tissue intended to be repaired. Through developing a biomaterial-free graft, it is possible to avoid these detrimental factors. And by using a patient's own stem cells it is possible to create native tissue that is fully biocompatible.

3D bioprinting was crucial to the development of effective cardiac patches, with specific spatial distribution being crucial to mechanical integrity. Cardiospheres without specific placement to overlap with other cardiospheres disintegrated after removal from the needle array; although partially disintegrated regions were able to fuse back together eventually. This effect removed the structural definition of the patch, negating the advantages of using bioprinting for developing a cardiac patch of specified dimensions.

The researchers grafted patches onto rat hearts and after a week saw signs of blood vessel formation, with viable cells and red blood cells present in the cardiac patch. Tissue protein stains showed that collagen was present in the patch, indicating the deposition of a native extracellular matrix from the cells, crucial to cell integration. Further staining showed the presence of human nucleic acid in rat tissue, implying that the human cell derived patch had successfully grafted with the rat tissue.

This biomaterial-free cardiac patch was developed using pluripotent cardiomyocyte stem cells, cardiac fibroblasts and human umbilical vein endothelial cells (HUVECs), which were aggregated into cardiospheroids for bioprinting. Cardiospheroids were able to develop a functional phenotype after 48 hours, with spontaneous beating and electrical conductivity a week after bioprinting. Cardiomyocytes alone were not able to reproduce this functional phenotype.

This process demonstrates a novel approach to eliminating biomaterial-induced damage. Further development of this 3D bioprinting technique in conjunction with stem cell therapies could progress biomaterial-free cardiac patches into the popular domain.

3D printers help build a better cranial nerve4D bioprinting: adding dynamic actuationThe first laser-printed 3D cellular tubes3D-printed polymer stents evolve

Geoffrey Potjewyd is a PhD Student contributor to medicalphysicsweb, working in the Division of Neuroscience and Experimental Psychology, as part of the CDT in Regenerative Medicine at The University of Manchester. He is studying the neurovascular unit in relation to vascular dementia and Alzheimer's disease, using biofabrication, biomaterials and stem cell based techniques.

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3D bioprinted cardiac patches are biomaterial free - Medical Physics Web (subscription)

Cardiac Stem Cells Comments Off on 3D bioprinted cardiac patches are biomaterial free – Medical Physics Web (subscription) | July 31st, 2017