Category Archives: Cell Medicine

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In a study that will provide the foundation for scientists to better replicate natural stem cell development in an artificial environment, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Guoping Fan, professor of human genetics, have established a benchmarking standard to assess how culture conditions used to procure stem cells in the lab compare to those found in the human embryo.

The study was published online ahead of print in the journal Cell Stem Cell.

Pluripotent stem cells (PSCs) are cells that can transform into almost any cell in the human body. Scientists have long cultured PSCs in the laboratory (in vitro) using many different methods and under a variety of conditions. Though it has been known that culture techniques can affect what kind of cells PSCs eventually become, no "gold standard" has yet been established to help scientists determine how the artificial environment can better replicate that found in a natural state (in vivo).

Dr. Kevin Huang, postdoctoral fellow in the lab of Dr. Fan and a lead author of the study, analyzed data from multiple existing research studies conducted over the past year. These previously published studies used different culture methods newly developed in vitro in the hopes of coaxing human stem cells into a type of pluripotency that is in a primitive or ground-zero state.

Utilizing recently-published gene expression profiles of human preimplantation embryos as the benchmark to analyze the data, Dr. Huang and colleagues found that culture conditions do affect how genes are expressed in PSCs, and that the newer generation culture methods appear to better resemble those found in the natural environment of developing embryos. This work lays the foundation on the adoption of standardized protocol amongst the scientific community.

"By making an objective assessment of these different laboratory techniques, we found that some may have more of an edge over others in better replicating a natural state," said Dr. Huang. "When you have culture conditions that more consistently match a non-artificial environment, you have the potential for a much better reflection of what is going on in actual human development."

With these findings, Dr. Fan's lab hopes to encourage further investigation into other cell characteristics and molecular markers that determine the effectiveness of culture conditions on the proliferation and self-renewal of PSCs.

"We hope this work will help the research community to reach a consensus to quality-control human pluripotent stem cells," said Dr. Fan.

Explore further: Technique to make human embryonic stem cells more closely resemble true epiblast cells

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Team proposes benchmark to better replicate natural stem cell development in the laboratory environment

PUBLIC RELEASE DATE:

23-Oct-2014

Contact: Scott LaFee slafee@ucsd.edu 619-543-6163 University of California - San Diego @UCSanDiego

In a push to further speed clinical development of emerging stem cell therapies, Sanford Stem Cell Clinical Center at UC San Diego Health System was named today one of three new "alpha clinics" by the California Institute for Regenerative Medicine (CIRM), the state's stem cell agency.

The announcement, made at a public meeting in Los Angeles of the CIRM Governing Board, includes an award of $8 million for each of three sites. The other alpha grant recipients are the City of Hope hospital near Los Angeles and University of California, Los Angeles.

"A UC San Diego alpha clinic will provide vital infrastructure for establishing a comprehensive regenerative medicine clinical hub that can support the unusual complexity of first-in-human stem cell-related clinical trials," said Catriona Jamieson, MD, PhD, associate professor of medicine at UC San Diego School of Medicine, deputy director of the Sanford Stem Cell Clinical Center, director of the UC San Diego Moores Cancer Center stem cell program and the alpha clinic grant's principal investigator.

"The designation is essential in much the same manner that comprehensive cancer center status is an assurance of scientific rigor and clinical quality. It will attract patients, funding agencies and study sponsors to participate in, support and accelerate novel stem cell clinical trials and ancillary studies for a range of arduous diseases."

The alpha clinics are intended to create the long-term, networked infrastructure needed to launch and conduct numerous, extensive clinical trials of stem cell-based drugs and therapies in humans, including some developed by independent California-based investigators and companies. These trials are requisite before any new drug or treatment can be approved for clinical use.

The clinics will also emphasize public education to raise awareness and understanding of stem cell science in part to combat "stem cell tourism" and the marketing of unproven, unregulated and potentially dangerous therapies and help establish sustainable business models for future, approved stem cell treatments.

"Everything we do has one simple goal, to accelerate the development of successful treatments for people in need," said C. Randal Mills, PhD, CIRM president and CEO. "Stem cell therapies are a new way of treating disease; instead of managing symptoms, cellular medicine has the power to replace or regenerate damaged tissues and organs. And so we need to explore new and innovative ways of accelerating clinical research with stem cells. That is what we hope these alpha stem cell clinics will accomplish."

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UC San Diego named stem cell 'alpha clinic'

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Newswise In a study that will provide the foundation for scientists to better replicate natural stem cell development in an artificial environment, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Guoping Fan, professor of human genetics, have established a benchmarking standard to assess how culture conditions used to procure stem cells in the lab compare to those found in the human embryo.

The study was published online ahead of print in the journal Cell Stem Cell.

Pluripotent stem cells (PSCs) are cells that can transform into almost any cell in the human body. Scientists have long cultured PSCs in the laboratory (in vitro) using many different methods and under a variety of conditions. Though it has been known that culture techniques can affect what kind of cells PSCs eventually become, no "gold standard" has yet been established to help scientists determine how the artificial environment can better replicate that found in a natural state (in vivo).

Dr. Kevin Huang, postdoctoral fellow in the lab of Dr. Fan and a lead author of the study, analyzed data from multiple existing research studies conducted over the past year. These previously published studies used different culture methods newly developed in vitro in the hopes of coaxing human stem cells into a type of pluripotency that is in a primitive or ground-zero state.

Utilizing recently-published gene expression profiles of human preimplantation embryos as the benchmark to analyze the data, Dr. Huang and colleagues found that culture conditions do affect how genes are expressed in PSCs, and that the newer generation culture methods appear to better resemble those found in the natural environment of developing embryos. This work lays the foundation on the adoption of standardized protocol amongst the scientific community.

"By making an objective assessment of these different laboratory techniques, we found that some may have more of an edge over others in better replicating a natural state," said Dr. Huang. "When you have culture conditions that more consistently match a non-artificial environment, you have the potential for a much better reflection of what is going on in actual human development."

With these findings, Dr. Fan's lab hopes to encourage further investigation into other cell characteristics and molecular markers that determine the effectiveness of culture conditions on the proliferation and self-renewal of PSCs.

"We hope this work will help the research community to reach a consensus to quality-control human pluripotent stem cells," said Dr. Fan.

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UCLA Scientists Propose Benchmark to Better Replicate Natural Stem Cell Development in the Laboratory Environment

UCSD oncologist/researcher Catriona Jamieson is principal investigator for the university's $8 million stem cell grant.

To speed up the quest to bring stem cell therapies to patients, a state agency on Thursday granted $8 million each to three academic medical centers pursuing "translational" work -- UC San Diego, UC Los Angeles and City of Hope in Duarte.

The California Institute for Regenerative Medicine voted 10-1 to fund the "alpha" stem cell clinics, which are intended to bring stem cell treatments to the public.

UC San Diego's proposal supports two stem cell-based clinical trials, both already underway. Catriona Jamieson, an oncologist at the university, is the principal investigator for the grant.

One, a treatment for Type 1 diabetes, was developed by San Diego's ViaCyte. The other, for spinal cord injuries, was developed by Geron of Menlo Park. Geron dropped the trial, but it was picked up by Neuralstem of Germantown, Md. In October, UCSD treated the first patient in the revived trial at the university's Sanford Stem Cell Clinical Center.

The stem cell agency, commonly called CIRM, has focused heavily on basic research since its founding by California voters in 2004. But in recent years, the public has become more anxious to see the fruits of $3 billion in bond money given to the agency reach patients. The "alpha" clinics funded Thursday are part of that effort.

Early optimism that treatments would be quickly available was disappointed, mainly because issues of safety had to be resolved first. Therapies that actually place cells in the body posed new risks, because as living things, cells grow and can migrate. Embryonic stem cells can form tumors. Viacyte and Neuralstem grow replacement tissues from embryonic stem cells, so they needed to show that no unconverted cells would accidentally be introduced into the patient.

Skepticism has also grown over the ethics of CIRM officials, mainly regarding conflicts of interests. Many CIRM board members are chosen from institutions that get funded -- a feature written into the agency by Prop. 71. CIRM has adopted reforms to limit board members from voting in matters where they have conflicts. But CIRM's previous president, Alan Trounson, caused more controversy when he joined the board of CIRM-funded Stemcells Inc, just one week after departing the agency.

CIRM President Randy Mills, who replaced Trounson earlier this year, has tried to quell the controversy with new standards to prevent officials like Trounson from appearing to cash in on their agency role. And he has worked with the governing board to rethink how the agency's remaining funds can be best spent.

CIRM has invested heavily in San Diego stem cell programs, most notably contributing $43 million to a $127 million "collaboratory" building across from the Salk Institute in La Jolla. The Sanford Consortium, as it's called, brings together researchers from five institutions: UCSD, the Salk Institute, The Scripps Research Institute, the Sanford-Burnham Medical Research Institute and the La Jolla Institute for Allergy & Immunology.

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UCSD, other stem cell clinics get millions

PUBLIC RELEASE DATE:

22-Oct-2014

Contact: David McKeon dmckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation @nyscf

NEW YORK, NY (October 22, 2014) The New York Stem Cell Foundation (NYSCF) Research Institute, through the launch of its repository in 2015, will provide for the first time the largest-ever number of stem cell lines available to the scientific research community. Initially, over 600 induced pluripotent stem (iPS) cell lines and 1,000 cultured fibroblasts from over 1,000 unique human subjects will be made available, with an increasing number available in the first year. To collect these samples, NYSCF set up a rigorous human subjects system that protects patients and allows for the safe and anonymous collection of samples from people interested in participating in research.

A pilot of over 200 of NYSCF's iPS cell lines is already searchable on an online database. The pilot includes panels of iPS cell lines generated from donors affected by specific diseases such as type 1 diabetes, Parkinson's disease, and multiple sclerosis, as well as a diversity panel of presumed healthy donors from a wide range of genetic backgrounds representing the United States Census. These panels, curated to provide ideal initial cohorts for studying each area, include subjects ranging in age of disease onset, and are gender matched. Other panels that will be available in 2015 include Alzheimer's disease, schizophrenia, Juvenile Batten disease, and Charcot-Marie-Tooth disease.

"NYSCF's mission is to develop new treatments for patients. Building the necessary infrastructure and making resources available to scientists around the world to further everyone's research are critical steps in accomplishing this goal," said Susan L. Solomon, CEO of The New York Stem Cell Foundation.

NYSCF has developed the technology needed to create a large collection of stem cell lines representing the world's population. This platform, known as the NYSCF Global Stem Cell ArrayTM, is an automated robotic system for stem cell production and is capable of generating 200 iPS cell lines a month from patients with various diseases and conditions and from all genetic backgrounds. The NYSCF Global Stem Cell ArrayTM is also used for stem cell differentiation and drug screening.

Currently available in the online database that was developed in collaboration with eagle-i Network, of the Harvard Catalyst, is a pilot set of approximately 200 iPS cell lines and related information about the patients. This open source, open access resource discovery platform makes the cell lines and related information available to the public on a user-friendly, web-based, searchable system. This is one example of NYSCF's efforts to reduce duplicative research and enable even broader collaborative research efforts via data sharing and analysis. NYSCF continues to play a key role in connecting the dots between patients, scientists, funders, and outside researchers that all need access to biological samples.

"The NYSCF repository will be a critical complement to other existing efforts which are limited in their ability to distribute on a global scale. I believe that this NYSCF effort wholly supported by philanthropy will help accelerate the use of iPS cell based technology," said Dr. Mahendra Rao, NYSCF Vice President of Regenerative Medicine.

To develop these resources, NYSCF has partnered with over 50 disease foundations, academic institutions, pharmaceutical companies, and government entities, including the Parkinson's Progression Markers Initiative (PPMI), PersonalGenomes.org, the Beyond Batten Disease Foundation, among several others. NYSCF also participates in and drives a number of large-scale multi stakeholder initiatives including government and international efforts. One such example is the Cure Alzheimer's Fund Stem Cell Consortium, a group consisting of six institutions, including NYSCF, directly investigating, for the first time, brain cells in petri dishes from individual patients who have the common sporadic form of Alzheimer's disease.

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The New York Stem Cell Foundation Research Institute announces largest-ever stem cell repository

PUBLIC RELEASE DATE:

20-Oct-2014

Contact: David McKeon 212-365-7440 New York Stem Cell Foundation @nyscf

Leaders in translational stem cell research from around the world will present the latest advances in stem cell science that are leading to better treatments and cures to disease and injury at The New York Stem Cell Foundation's Ninth Annual Translational Stem Cell Research Conference.

The opening day of the conference includes a panel discussion on large scale, big data stem cell and genetic initiatives moderated by Susan L. Solomon, JD, CEO and Co-founder of The New York Stem Cell Foundation (NYSCF), with panelists George Church, PhD, Harvard Medical School; John Greally, PhD, Albert Einstein College of Medicine; Scott Noggle, PhD, The NYSCF Research Institute; and Eric Schadt, PhD, the Icahn School of Medicine at Mount Sinai.

Later that day, a discussion on neurodegeneration includes Kevin Eggan, PhD, Harvard University and the NYSCF Research Institute, who will discuss his research identifying an existing drug candidate that may be of use treating ALS and is entering clinical trials in the coming year. The following session on cell reprogramming and cancer includes Michael Milone, MD, PhD, University of Pennsylvania, who will discuss recent research results from his lab and his colleagues including the results of a clinical trial for leukemia featured in The New York Times last week. The first day closes with a conversation on personalized medicine featuring Dieter Egli, PhD, NYSCF Robertson Investigator at the NYSCF Research Institute and Columbia University; Rudolf Jaenisch, MD, The Whitehead Institute; and Sir Ian Wilmut, FRS, FRSE, University of Edinburgh.

On October 23, the day will begin with remarks by Kenneth Adams and Kyle Kimball, President of the Empire State Development Corporation and President of the New York City Economic Development Corporation, respectively. The session on translating innovation from the laboratory to the clinic features Stephen Chang, PhD, of the NYSCF Research Institute and Richard Pearse, PhD, of the Harvard Catalyst and eagle-i Network who will discuss their collaboration on the first publicly available induced pluripotent stem cell database. The day will close with a presentation on induced neuronal cells and cell transdifferentiation from the 2014 NYSCF Robertson Stem Cell Prize recipient, Marius Wernig, MD, PhD, of Stanford University School of Medicine.

Sir Ian Wilmut will give the keynote address on October 22nd and Dr. Rudolf Jaenisch will give the keynote address on the last day of the conference.

The full conference agenda can be found at http://www.nyscf.org/conference

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Stem cell and clinical research advances to be presented at NYSCF's Ninth Annual Conference

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Newswise Scientists have described a way to convert human skin cells directly into a specific type of brain cell affected by Huntingtons disease, an ultimately fatal neurodegenerative disorder. Unlike other techniques that turn one cell type into another, this new process does not pass through a stem cell phase, avoiding the production of multiple cell types, the studys authors report.

The researchers, at Washington University School of Medicine in St. Louis, demonstrated that these converted cells survived at least six months after injection into the brains of mice and behaved similarly to native cells in the brain.

Not only did these transplanted cells survive in the mouse brain, they showed functional properties similar to those of native cells, said senior author Andrew S. Yoo, PhD, assistant professor of developmental biology. These cells are known to extend projections into certain brain regions. And we found the human transplanted cells also connected to these distant targets in the mouse brain. Thats a landmark point about this paper.

The work appears Oct. 22 in the journal Neuron.

The investigators produced a specific type of brain cell called medium spiny neurons, which are important for controlling movement. They are the primary cells affected in Huntingtons disease, an inherited genetic disorder that causes involuntary muscle movements and cognitive decline usually beginning in middle-adulthood. Patients with the condition live about 20 years following the onset of symptoms, which steadily worsen over time.

The research involved adult human skin cells, rather than more commonly studied mouse cells or even human cells at an earlier stage of development. In regard to potential future therapies, the ability to convert adult human cells presents the possibility of using a patients own skin cells, which are easily accessible and wont be rejected by the immune system.

To reprogram these cells, Yoo and his colleagues put the skin cells in an environment that closely mimics the environment of brain cells. They knew from past work that exposure to two small molecules of RNA, a close chemical cousin of DNA, could turn skin cells into a mix of different types of neurons.

In a skin cell, the DNA instructions for how to be a brain cell, or any other type of cell, is neatly packed away, unused. In past research published in Nature, Yoo and his colleagues showed that exposure to two microRNAs called miR-9 and miR-124 altered the machinery that governs packaging of DNA. Though the investigators still are unraveling the details of this complex process, these microRNAs appear to be opening up the tightly packaged sections of DNA important for brain cells, allowing expression of genes governing development and function of neurons.

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Human Skin Cells Reprogrammed Directly Into Brain Cells

PUBLIC RELEASE DATE:

16-Oct-2014

Contact: Anita Srikameswaran SrikamAV@upmc.edu 412-578-9193 University of Pittsburgh Schools of the Health Sciences @UPMCnews

PITTSBURGH, Oct. 16, 2014 Despite previous indications to the contrary, the esophagus does have its own pool of stem cells, said researchers from the University of Pittsburgh School of Medicine in an animal study published online today in Cell Reports. The findings could lead to new insights into the development and treatment of esophageal cancer and the precancerous condition known as Barrett's esophagus.

According to the American Cancer Society, more than 18,000 people will be diagnosed with esophageal cancer in the U.S. in 2014 and almost 15,500 people will die from it. In Barrett's esophagus, the lining of the esophagus changes for unknown reasons to resemble that of the intestine, though gastro-esophageal reflux disease or GERD is a risk factor for its development.

"The esophageal lining must renew regularly as cells slough off into the gastrointestinal tract," said senior investigator Eric Lagasse, Pharm.D., Ph.D., associate professor of pathology, Pitt School of Medicine, and director of the Cancer Stem Cell Center at the McGowan Institute for Regenerative Medicine. "To do that, cells in the deeper layers of the esophagus divide about twice a week to produce daughter cells that become the specialized cells of the lining. Until now, we haven't been able to determine whether all the cells in the deeper layers are the same or if there is a subpopulation of stem cells there."

The research team grew pieces or "organoids" of esophageal tissue from mouse samples, and then conducted experiments to identify and track the different cells in the basal layer of the tissue. They found a small population of cells that divide more slowly, are more primitive, can generate specialized or differentiated cells, and have the ability to self-renew, which is a defining trait of stem cells.

"It was thought that there were no stem cells in the esophagus because all the cells were dividing rather than resting or quiescent, which is more typical of stem cells," Dr. Lagasse noted. "Our findings reveal that there indeed are esophageal stem cells, and rather than being quiescent, they divide slowly compared to the rest of the deeper layer cells."

In future work, the researchers will examine human esophageal tissues for evidence of stem cell dysfunction in Barrett's esophagus disease.

"Some scientists have speculated that abnormalities of esophageal stem cells could be the origin of the tissue changes that occur in Barrett's disease," Dr. Lagasse said. "Our current and future studies could make it possible to test this long-standing hypothesis."

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Pitt/McGowan Institute team discovers stem cells in the esophagus

41 minutes ago by Vicky Just Naive-like stem cells could potentially be used to treat dementia or reduce organ transplants

Scientists from our university and Berlin have identified a type of human stem cell that appears to be "nave-like" able to develop into any type of cell. The discovery of this cell type could potentially have a large impact on our understanding of how humans develop and on the field of regenerative medicine.

The human embryonic stem cells (ESCs) that scientists currently study in the lab are able to develop into several different types of cell but are already pre-determined to some extent.

Published in the top scientific journal Nature, researchers from the Max Delbrck Centre for Molecular Medicine (MDC), Berlin, Germany and our university have for the first time discovered human ESCs that appear to behave like "nave" cells able to develop into any type of cell.

These nave-like cells, only previously found in mice, are easy to grow in the lab and could have huge potential for regenerating damaged tissues in the body, potentially leading to treatments for diseases such as dementia or reducing the need for organ transplantation.

Professor Laurence Hurst from our Department of Biology & Biochemistry and a co-author of the study explained: "Most stem cells are primed to some extent to become a certain type of cell. If you use the analogy of a train network, these cells are like one of the main London stations. Trains from Paddington can go to Cardiff or Exeter, but not to Norwich. In the same way, these cells can develop into a fixed number of different cell types.

"However the nave-like cells we've identified are like a central terminus; they are present earlier in the embryo's development and so we think their fates can go in any direction and become any type of cell."

Co-investigator Dr Zsuzsanna Izsvk, (MDC, corresponding author) said: "We were very excited by this discovery it was one of those Eureka moments that rarely happens in science."

The Bath and Berlin team found the nave-like cells by looking at which genes were expressed in very early human embryos. They pinpointed a virus called human endogenous retrovirus H (HERVH) that has become integrated into human DNA and was very highly expressed at just the right time and place in human embryos, where they would expect to see nave-like cells if they existed.

They identified a protein called LBP9, which is essential for the activity of HERVH in early embryos. Using a reporter system that made cells expressing HERVH via LBP9 glow green, the Berlin and our team found that they had purified cells that showed all of the hallmarks of a mouse nave cell.

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Scientists identify "nave-like" human stem cell

Dr. Deepak Srivastava, a leading biomedical research policy expert, will discuss "Stem Cells, Regenerative Medicine and Policy Impediments to the New Future" at Rice University's Baker Institute for Public Policy Oct. 21. The event is free and open to the public, but registration is required.

Who: Dr. Deepak Srivastava, the Baker Institute's nonresident scholar for biomedical research policy and the Younger Family Director and senior investigator at the Gladstone Institute of Cardiovascular Disease.

Neal Lane, the Malcolm Gillis University Professor, senior fellow in science and technology policy at Rice's Baker Institute for Public Policy and a professor of physics and astronomy, will give introductory remarks.

Stem cells and regenerative medicine are exciting and emerging fields of biomedical research, according to event organizers. Proposed applications include treating conditions such as blindness, diabetes and heart disease. Regenerative medicine could also help heal failing organ systems and replace damaged tissue. While these fields hold great promise for medicine, external factors limit and, in some cases, stall research, organizers said. Ethical controversies surrounding human embryonic stem cells, policy issues affecting federal and state funding and regulation, and economic pressures all play a role in determining the future of research.

In his presentation, Srivastava will explore the current and future potential of stem cells and regenerative medicine. Following the presentation, he will discuss policy challenges and opportunities with Lane.

The event is sponsored by the Baker Institute's Science and Technology Policy Program and the Health Policy Forum.

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Stem cell, regenerative medicine policies to be discussed at Rice's Baker Institute