Archived News

Thursday, January 19, 2012 -

 

 

 

January 18, 2012

CONTACT: Karen Kreeger
215-349-5658
karen.kreeger@uphs.upenn.edu

 


This release is available online at
http://www.uphs.upenn.edu/news/News_Releases/2012/01/lung-biologists-award/

 

Penn Lung Biologists to Receive $2.5 Million to Study Repair and Regeneration

PHILADELPHIA – The Perelman School of Medicine at the University of Pennsylvania is one of six institutions to be named part of the National Heart, Lung, and Blood Institute’s Lung Repair and Regeneration Consortium (LRRC). Each of the institutions will receive $2.5 million over five years. Edward Morrisey, PhD, professor of Medicine and Cell and Developmental Biology and Scientific Director of the Penn Institute for Regenerative Medicine, will lead the Penn consortium.

Lung disease is a leading cause of death and disease in the world, and diseases of the lung such as asthma and chronic obstructive pulmonary disease (COPD) are on the rise. The consortium will bring together investigators whose expertise spans basic science through translational medicine to study lung repair and tissue regeneration to fight lung diseases.

Asthma and COPD are chronic lung diseases that affect the bronchiolar airways of the lung and are leading causes of morbidity and mortality. Both diseases are thought to involve a chronic injury-repair cycle that leads to the eventual breakdown of normal airway structure and function.

The Penn grant will study the epigenetic control of lung repair and regeneration with a focus on chromatin remodeling factors and microRNA pathways. Epigenetics involves chemical modifications to DNA and its supporting proteins that affect gene expression.

Co-investigators at Penn, including Jonathan Epstein, MD, chair, Department of Cell and Developmental Biology; Rey A. Panettieri, Jr., MD, professor of Medicine; and Paul Gadue, PhD, assistant professor of Pathology and Laboratory Medicine, will work with Dr. Morrisey to explore the role of pathways involving the enzyme histone deacetylase and microRNAs, both of which are part of the epigenetics molecular machinery.

To apply regenerative medicine techniques to lung disease, the team aims to identify and characterize cell types that affect lung repair and regeneration and to learn how to maintain, grow, and differentiate the cells into mature and functioning airway epithelial cells. The team will also focus on using small molecule mediators of histone deacetylase activity and microRNAs to develop new therapies to alleviate the unmet needs of patients with asthma and COPD, as well as other airway diseases.

###

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

Monday, December 12, 2011 -

FOR IMMEDIATE RELEASE

Contact:
Karen Kreeger
215-349-5658

Karen.kreeger@uphs.upenn.edu 

Reprogramming Brain Cells Important First Step for New Parkinson’s Therapy, Penn Study Finds
Researchers convert astrocytes directly into dopamine-producing nerve cells of the midbrain

PHILADELPHIA - In efforts to find new treatments for Parkinson’s Disease (PD), researchers from the Perelman School of Medicine at the University of Pennsylvania have directly reprogrammed astrocytes, the most plentiful cell type in the central nervous system, into dopamine-producing neurons. PD is marked by the degeneration of dopaminergic neurons in the midbrain. Dopamine is a brain chemical important in behavior and cognition, voluntary movement, sleep, mood, attention, and memory and learning.

“These cells are potentially useful in cell-replacement therapies for Parkinson’s or in modeling the disease in the lab,” says senior author John Gearhart, PhD, director of the Institute for Regenerative Medicine (IRM) at Penn. The team reports their findings in PLoS One.

“Our study is the first to demonstrate conversion of astrocytes to midbrain dopaminergic neurons, opening the door for novel reprogramming strategies to treat Parkinson’s disease,” says first author Russell C. Addis, PhD, a senior research investigator at IRM.

A Different Approach

Parkinson’s affects different areas of the brain but primarily attacks the dopamine-producing section called the substantial nigra. Cells in this region send dopamine to another region called the striatum, where it is used to regulate movement. The chemical or genetic triggers that kill dopamine neurons over time is at the heart of understanding the progressive loss of these specialized cells.

As many as one million people in the US live with Parkinson's Disease, according to the Parkinson’s Disease Foundation. Symptoms include tremors, slowness of movements, limb stiffness, and difficulties with gait and balance.

Limited success in clinical trials over the last 15 years in transplanting fetal stem cells into the brains of Parkinson’s disease patients has spurred researchers to look for new treatments. Using PET scans, investigators have been able to see that transplanted neurons grow and make connections, reducing symptoms for a time. Ethical issues about the source of embryonic stem cells; the interaction of cells with host cells; the efficiency of stems cells to reproduce, and their long-term viability and stability are all still concerns about trials using dopaminergic cell transplants to treat Parkinson’s.

First Steps

In the first step towards a direct cell replacement therapy for Parkinson’s, the team reprogrammed astrocytes to dopaminergic neurons using three transcription factors – ASCL1, LMX1B, and NURR1 – delivered with a lentiviral vector.

The process is efficient, with about 18 percent of cells expressing markers of dopaminergic neurons after two weeks. The next closest conversion efficiency is approximately 9 percent, which was reported in another study.

The dopamine-producing neurons derived from astrocytes showed gene expression patterns and electrophysiolgical properties of midbrain dopaminergic neurons, and released dopamine when their cell membranes were depolarized.

The Penn team is now working to see if the same reprogramming process that converts astrocytes to dopamine-producing neurons in a dish can also work within a living brain – experiments will soon be underway using gene therapy vectors to deliver the reprogramming factors directly to astrocytes in an animal model of PD.

This project is funded, in part, under a grant with the Pennsylvania Department of Health (PDH). The PDH specifically disclaims responsibility for any analyses, interpretations, or conclusions.  Additional support was provided by the Penn Institute for Regenerative Medicine. Co-authors, in addition to Gearhart and Addis, are Rebecca L. Wright and Marc A. Dichter from Penn and Fu-Chun Hsu and Douglas A. Coulter, from the Children’s Hospital of Philadelphia.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

Tuesday, November 15, 2011 -

 Efforts to use stem cells to help revitalize hearts damaged by heart attack got a boost from three studies presented Monday at the annual meeting of the American Heart Association. The studies looked at infusing bone marrow stem cells into the heart soon after a heart attack might improve survival, and how cardiac stem cells might also come to the aid of patients battling heart failure. The results are promising, but several experts urged caution in interpreting the results. In an interview for USNews & World Report, Kenneth B. Margulies, MD, director, Heart Failure and Transplant Research and professor of Medicine, cautioned that the research is in its infancy, and more studies are needed.

http://health.usnews.com/health-news/family-health/heart/articles/2011/11/14/stem-cells-show-promise-in-healing-damaged-hearts?PageNr=1

Monday, November 14, 2011 -

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH NewsNational Heart, Lung, and Blood Institute (NHLBI) <http://www.nhlbi.nih.gov/>
For Immediate Release: Embargoed for Release: November 14, 2011, 9 a.m. EST

CONTACT: NHLBI Communications, 301-496-4236,
<e-mail:NHLBI_news@nhlbi.nih.gov>

DELAYED STEM CELL THERAPY FOLLOWING HEART ATTACK IS SAFE BUT NOT EFFECTIVE 

NIH-funded trial shows that therapy with bone-marrow derived cells does not improve heart function after six months; future clinical benefits still possible.

Stem cells obtained from bone marrow, known as BMCs, can be safely injected into people 2-3 weeks following a heart attack, reports a new clinical trial supported by the National, Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. However, while safe, the BMCs did not improve heart function six months after their administration.

This study, called LateTIME (Transplantation In Myocardial Infarction Evaluation), is the first trial to rigorously examine the safety and potential benefits of extending the timing of stem cell delivery to 2-3 weeks following a heart attack. The results will be presented Monday, Nov. 14, at the 2011 Scientific Sessions of the American Heart Association Meeting in Orlando, Fla. They will also appear online in the Journal of the American Medical Association.

"Although treatment and survival following a heart attack have improved over the years, the risk of heart failure following a heart attack has not decreased," said Susan B. Shurin, M.D., acting director of the NHLBI. "Stem cell therapy is a promising direction for repairing the damage done by a heart attack.  We do not fully understand the optimal use of these cells; studies like LateTIME will help us understand how to perform and monitor these procedures.''   

Previous studies have suggested that injecting BMCs into the heart could improve cardiac function following a heart attack and perhaps reduce the need for future hospitalizations and heart surgeries. In contrast to LateTIME, earlier studies delivered BMCs within a few days of the heart attack. In many cases, a patient will not be able to get such immediate treatment, due to poor health following a heart attack or because the hospital providing care doesn't have a stem cell therapy program.

Between July 2008 and February 2011, LateTIME enrolled 87 people with heart attacks who had undergone cardiac procedures to open blocked arteries. The participants all had moderate to severe impairment in their left ventricle, which pumps oxygen-rich blood to the body.  All the participants had stem cells taken from bone marrow in their hip for processing. LateTIME researchers developed a standardized method of processing and purifying these stem cells, and this was the first BMC trial to provide a uniform dose of BMCs to each participant. The study then randomly assigned the participants to receive either their purified BMCs or inactive (placebo) cells.

After six months, improvement of heart function was assessed by measuring the percentage of blood that gets pumped out of the left ventricle during each contraction (left-ventricular ejection fraction, or LVEF) by cardiac MRI. There were no significant differences between the change in LVEF readings between baseline and six months in the BMC (from 48.7 percent to 49.2 percent) or placebo (from 45.3 percent to 48.8 percent) groups.

"This does not mean that stem cell therapy will only work if done immediately following a heart attack or that later beneficial effects on clinical outcomes won't emerge," noted Lemuel A. Moyé, M.D., Ph.D., professor of biostatistics at the University of Texas School of Public Health, Houston, and a LateTIME researcher. "Many factors influence how the heart responds to stem cells, which highlights the critical need to continue rigorous tracking studies in this area."

Moyé added that the health of the study participants will continue to be evaluated for two years, so the BMC therapy may yet demonstrate health benefits such as a lower risk of subsequent heart attacks or heart failure, in which the heart cannot pump enough blood to meet the body's needs.  

LateTIME is one of three heart stem cell trials being undertaken by the NHLBI-sponsored Cardiovascular Cell Therapy Research Network. The other trials under way by this multicenter consortium are TIME, which is comparing the effectiveness of stem cell therapy delivered at three days versus seven days following a heart attack, and FOCUS, which is examining stem cell therapy in people with chronic heart failure.

To schedule an interview with an NHLBI spokesperson, contact the NHLBI Office of Communications at 301-496-4236 or <NHLBI_news@nhlbi.nih.gov>.

The National Heart, Lung, and Blood Institute (NHLBI) is a component of the National Institutes of Health. NHLBI plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at: <www.nhlbi.nih.gov>.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <www.nih.gov>.

---------------------------------

RESOURCES:

-- What is a heart attack:
<http://www.nhlbi.nih.gov/health/health-topics/topics/heartattack/>

-- What is heart failure:
<http://www.nhlbi.nih.gov/health/health-topics/topics/hf/>

-- What is coronary angioplasty:
<http://www.nhlbi.nih.gov/health/health-topics/topics/angioplasty/>

-- Cardiovascular Cell Therapy Research Network website
<www.cctrn.org >

##

This NIH News Release is available online at:
<http://www.nih.gov/news/health/nov2011/nhlbi-14.htm>
.

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Friday, November 11, 2011 -

 

November 10, 2011

CONTACT: Karen Kreeger
215-349-5658
karen.kreeger@uphs.upenn.edu

Penn Medicine - University of Pennsylvania School of Medicine and University of Pennsylvania Health System


This release is available online at
http://www.uphs.upenn.edu/news/News_Releases/2011/11/gut-cell-regen/

 

Tales from the Crypt: Penn Study on Gut Cell Regeneration Reconciles Long-Standing Research Controversy

Implications for Tissue Regeneration, Colon Cancer

PHILADELPHIA - The lining of the intestine regenerates itself every few days as compared to say red blood cells that turn over every four months. The cells that help to absorb food and liquid that humans consume are constantly being produced. The various cell types that do this come from stem cells that reside deep in the inner recesses of the accordion-like folds of the intestines, called villi and crypts.

But exactly where the most important stem cell type is located -- and how to identify it -- has been something of a mystery. In fact, two types of intestinal stem cells have been proposed to exist but the relationship between them has been unclear. One type of stem cell divides slowly and resides at the sides of intestinal crypts. The other divides much more quickly and resides at the bottom of the crypts.

Some researchers have been proponents of one type of stem cell or the other as the "true" intestinal stem cell. Recent work published this week in Science from the lab of Jonathan Epstein, MD, chairman of the Department of Cell and Developmental Biology from the Perelman School of Medicine at the University of Pennsylvania, may reconcile this controversy. The findings suggest that these two types of stem cells are related. In fact, each can produce the other, which surprised the researchers.

"We actually began our studies by looking at stem cells in the heart and other organs," Epstein said.  "In other tissues in the body, slowly dividing cells can sometimes give rise to more rapidly dividing stem cells that are called to action when tissue regeneration is required.  Our finding that this can happen in reverse in the intestine was not expected."

The discovery that rapidly cycling gut stem cells can regenerate the quiescent stem cells -- slowly dividing and probably long-lived -- suggests that the developmental pathways in human organs that regenerate quickly like in the gut, skin, blood, and bone, may be more flexible than previously appreciated.

"This better appreciation and understanding may help us learn how to promote the regeneration of tissue-specific adult stem cells that could subsequently help with tissue regeneration," says Epstein.  "It may also help us to understand the cell types that give rise to cancer in the colon and stomach."

Co-authors are, all from Penn, Norifumi Takeda, Rajan Jain, Matthew R. LeBoeuf, Qiaohong Wang, and Min Min Lu.  The work was funded by the National Heart, Lung and Blood Institute of the National Institutes of Health and by the Penn Institute for Regenerative Medicine.

###

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

 

Wednesday, October 26, 2011 -

PHILADELPHIA - The pigmented cells called melanocytes aren't just for making freckles and tans. Melanocytes absorb ultraviolet light, protecting the skin from the harmful effects of the sun. They also are the cells that go haywire in melanoma, as well as in more common conditions as vitiligo and albinism.

Naturally, researchers would love to study melanocytes in the laboratory. There's just one problem -- melanocytes from adult skin don't grow very well in the lab. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania have found a way to create melanocytes from mouse tail cells using embryonic stem cell-like intermediates called inducible pluripotent (iPS) cells.

Xiaowei Xu, MD, PhD, associate professor of Pathology and Laboratory Medicine, is senior author the study, which appears online in the Journal of Investigative Dermatology ahead of the December print issue. Xu and his team converted mouse tail-tip fibroblasts into iPS cells using four genes, which were first described by Shinya Yamanaka in 2006, producing pluripotent cells similar to embryonic stem cells, but without the concomitant ethical issues.

According to Xu, these lab-made melanocytes promise benefits in areas from tissue transplantation to drug discovery. "This method really has lots of clinical implications," says Xu. "We are not quite there yet, but this is an early step."

For example, by collecting a tissue sample from patients with, say, vitiligo, and converting it to iPS cells, researchers can study what goes wrong as those cells differentiate into melanocytes. Or, they can study the development and possible treatment of melanoma.

Xu's new study is the first to report creating melanocytes from iPS cells in mice, and builds on his previous work. Xu's lab was involved in the first study to work out the conditions for differentiating human embryonic stem cells to melanocytes in 2006. Earlier this year, a Japanese team became the first to differentiate human iPS cells to melanocytes.

Transformation of Cells
Initially, the researchers from Xu’s lab introduced the four Yamanaka genes into mouse cells by infecting the cells with transgenic viruses. Between 0.5% to 0.8% of fibroblasts treated in this way converted to iPS cells in Xu's lab – a rate that is consistent with other researchers' findings, he says. But his team also could achieve the same result (albeit at lower efficiency, 0.01%) using a non-viral "transposon" called piggyBac. Finally, the researchers showed they could differentiate both iPS cell populations into melanocytes in about two weeks by feeding the cells a defined cocktail of growth factors.

According to Xu, the growth factor cocktail used in the present study differs somewhat from the formulation his lab worked out several years ago for human embryonic stem cells. Among other things, it works in the absence of the growth factor Wnt3a and the carcinogen TPA, both of which are required for human melanocyte differentiation. TPA, especially, could be problematic for possible cell-based therapies, in that it is tumorigenic. It remains to be seen, however, whether human iPS cells can also be differentiated in the absence of this compound, Xu notes.

His study's implementation of piggyBac in creating the iPS cells (a technique first published by Canadian researchers in 2009) could possibly extend the technique's clinical value, he adds. Unlike viruses, which insert their genetic cargo into the host genome, thereby raising concerns of genetic alterations in the infected cells, piggyBac delivers genes without permanently altering the host genome.

Other authors include Penn researchers Ruifeng Yang, Min Jiang, Suresh Kumar, and Ted Xu, as well as Fei Wang of the University of Illinois, Urbana-Champaign and Leihong Xiang of Fudan University, Shanghai.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin.

###

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

Wednesday, August 3, 2011 -

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
NIH Office of the Director (OD) <http://www.nih.gov/icd/od/>

For Immediate Release: Tuesday, August 3, 2011

CONTACT: NIH News Media Branch, NIH OCPL, 301-496-5787,  <e-mail:nihnmb@mail.nih.gov>

NIH APPOINTS DIRECTOR OF INTRAMURAL CENTER FOR REGENERATIVE MEDICINE

National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has announced the appointment of Mahendra S. Rao, M.D., Ph.D. as the director for the new NIH Intramural Center for Regenerative Medicine (NIH-CRM).  The NIH-CRM is an initiative to create a world-class center of excellence in stem cell technology on the NIH campus, including induced pluripotent stem cells (iPSC), which can have applications in many systems and organs of the body. This is an initiative of the NIH Common Fund and will be administered by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

“Dr. Rao’s varied experience makes him perfectly qualified to bring large groups together in order to move stem cell technologies through clinical trials and beyond to the clinic,” Collins said.

A major goal for the center is to build upon existing NIH investments in stem cell research to advance translational studies and ultimately cell-based therapies in the NIH Clinical Center. The center will also serve as a resource for the scientific community, providing stem cells, as well as the supporting protocols and standard operating procedures used to derive, culture, and differentiate them into different cell types.

In addition to his NIH-CRM Director position, Dr. Rao will hold a joint research appointment in NIAMS and the National Institute of Neurological Disorders and Stroke (NINDS).

NIAMS Scientific Director Dr. John O’Shea noted, “Dr. Rao is an ideal choice to lead the NIH-CRM at this pivotal time for stem cell research. His unique background will serve him and the center well as we move forward to fulfill the great promise of stem cell technology.”

“I am delighted that Dr. Rao has been selected to lead NIH-CRM,” said Story C. Landis, Ph.D., NINDS director and chair of the NIH Stem Cell Task force. “He brings extensive experience with human stem cells to the position as well as considerable energy and focus on moving to clinical applications.” 

Dr. Rao is internationally renowned for his research involving human embryonic stem cells (hESCs) and other somatic stem cells. He has worked in the stem cell field for more than 20 years, with stints in academia, government and regulatory affairs and industry. He received his M.D. from Bombay University in India and his Ph.D. in developmental neurobiology from the California Institute of Technology, Pasadena. Following postdoctoral training at Case Western Reserve University, Cleveland, he established his research laboratory in neural development at the University of Utah, Salt Lake City. He next joined the National Institute on Aging as chief of the Neurosciences Section, where he studied neural progenitor cells and continued to explore his longstanding interest in their clinical potential. Most recently, he spent six years as the vice president of Regenerative Medicine at Life Technologies, Carlsbad, Calif. He co-founded Q Therapeutics, a neural stem cell company based in Salt Lake City. He also served internationally on advisory boards for companies involved in stem cell processing and therapy, on committees including the U.S. Food and Drug Administration’s Cellular Tissue and Gene Therapies Advisory Committee chair, and as the California Institute of Regenerative Medicine and International Society for Stem Cell Research liaison to the International Society for Cellular Therapy.

The Office of the Director, the central office at NIH, is responsible for setting policy for NIH, which includes 27 Institutes and Centers. This involves planning, managing, and coordinating the programs and activities of all NIH components. The Office of the Director also includes program offices which are responsible for stimulating specific areas of research throughout NIH. Additional information is available at <http://www.nih.gov/icd/od/>.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <www.nih.gov>.

##

This NIH News Release is available online at:

<http://www.nih.gov/news/health/aug2011/od-03.htm>.

Tuesday, June 21, 2011 -

High school students, teachers, and Penn mentors from the IRM's Bridge to ReBIO program participated in a round-table discussion about science outreach, as part of the education session at this year's Mid-Atlantic Society for Developmental Biology Meeting, hosted by Penn on June 3rd-5th.  Panelists and developmental biologists from around the region discussed the benefits and challenges involved with creating effective science outreach projects, while emphasizing the importance of such outreach work to both the public and to scientists.  High school students participating in the conference then stayed to present their Bridge to ReBIO projects at the meeting's poster session.

Bridge to ReBIO has been made possible by the receipt of tobacco settlement funds at the University of Pennsylvania.  More information can be found at the Pennsylvania Department of Health’s Website for health research grants program at www.health.state.pa.us/cure.

 

Friday, May 20, 2011 -

This release is available online at http://www.uphs.upenn.edu/news/News_Releases/2011/05/personalized-cells/

Predicting the Fate of Personalized Cells Next Step Towards New Therapies, Penn Study Suggests

PHILADELPHIA — Discovering the step-by-step details of the path embryonic cells take to develop into their final tissue type is the clinical goal of many stem cell biologists.

To that end, Kenneth S. Zaret, PhD, of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, and associate director of the Penn Institute for Regenerative Medicine, and Cheng-Ran Xu, PhD, a postdoctoral researcher in the Zaret laboratory, looked at immature cells called progenitors and found a way to potentially predict their fate. They base this on how the protein spools around which DNA winds -- called histones -- are marked by other proteins. This study appeared this week in Science.

In the past, researchers grew progenitor cells and waited to see what they differentiated into. Now, they aim to use this marker system, outside of a cell's DNA and genes, to predict the cell’s eventual fate. This extra-DNA system of gene expression control is called epigenetics. 

"We were surprised that there's a difference in the epigenetic marks in the process for liver versus pancreas before the cell-fate 'decision' is made." says Zaret. "This suggests that we could manipulate the marks to influence fate or look at marks to better guess the fate of cells early in the differentiation process."

"How cells become committed to particular fates is a fundamental question in developmental biology," said Susan Haynes, PhD, program director in the Division of Genetics and Developmental Biology at the National Institutes of Health, which funds this line of research. "This work provides important new insights into the early steps of this process and suggests new approaches for controlling stem-cell fate in regenerative medicine therapies."

A Guiding Path

How the developing embryo starts to apportion different functions to different cell types is a key question for developmental biology and regenerative medicine. Guidance along the correct path is provided by regulatory proteins that attach to chromosomes, marking part of the genome to be turned on or off. But first the two meters of tightly coiled DNA inside the nucleus of every cell must be loosened a bit. Regulatory proteins help with this, exposing a small domain near the target gene.

Chemical signals from neighboring cells in the embryo tell early progenitor cells to activate genes encoding proteins. These, in turn, guide the cells to become liver or pancreas cells, in the case of Zaret's work. Over several years, his lab has unveiled a network of the common signals in the mouse embryo that govern development of these specific cell types.

Zaret likens the complexity of this system to the 26-letter alphabet being able to encode Shakespeare or a menu at a restaurant. Many investigators are now trying to broadly reprogram cells into desired cell fates for potential therapeutic uses.

The researchers had previously shown that a particular growth factor that attaches to the cell surface, gives a specific chemical signal for cell-type fate, promoting development along the liver-cell path and suppressing development along the pancreas-cell path. Liver and pancreas cells originate from a common progenitor cell.

Zaret's group figured out which enzymes -- called histone acetyl transferases or methyl transferases (that add methyl groups or acetyl groups to histones) are relevant to the pancreas arm of the liver-pancreas fate decision. They used mice in which they knocked out the function for one enzyme type versus the other to induce the development of fewer liver cells and more pancreas cells.

The transferases mark genes for liver and pancreas fates differently before a cell moves into the next intermediate type along the way to becoming a mature liver or pancreas cell.

Investigators want to make embryonic stem cells for liver or pancreatic beta cells for therapies and research. To do this, they mimic the embryonic developmental steps to proceed from an embryonic stem cell to a mature cell, but have no way of knowing if they are on the right track. The hope is that the findings from this study can be applied to assess the epigenetic state of intermediate progenitor cells.

"By better understanding how a cell is normally programmed we will eventually be able to properly reprogram other cells," notes Zaret. In the near term, the team also aims to generate liver and pancreas cells for research and to screen drugs that repair defects or facilitate cell growth.

With regenerated cells, researchers hope to one day fill the acute shortage in pancreatic and liver tissue available for transplantation in cases of type I diabetes and acute liver failure.

The research was funded by the Institute of General Medical Sciences and the Institutes for Diabetes, Digestive, and Kidney Disorders.

Friday, April 8, 2011 -

April 7, 2011
CONTACT: Karen Kreeger
215-349-5658
karen.kreeger@uphs.upenn.edu           

This release and a related image and video are available online at http://www.uphs.upenn.edu/news/News_Releases/2011/04/efficient-reprogrammed-stem-cells/

A New Way to Make Reprogrammed Stem Cells

Penn study eliminates the use of transcription factors and increases efficiency 100-fold

PHILADELPHIA - Researchers at the University of Pennsylvania School of Medicine have devised a totally new and far more efficient way of generating induced pluripotent stem cells (iPSCs), immature cells that are able to develop into several different types of cells or tissues in the body. The researchers used fibroblast cells, which are easily obtained from skin biopsies, and could be used to generate patient-specific iPSCs for drug screening and tissue regeneration.

iPSCs are typically generated from adult non-reproductive cells by expressing four different genes called transcription factors.  The generation of iPSCs was first reported in 2006 by Shinya Yamanaka, and multiple groups have since reported the ability to generate these cells using some variations on the same four transcription factors.

The promise of this line of research is to one day efficiently generate patient-specific stem cells in order to study human disease as well as create a cellular "storehouse" to regenerate a person's own cells, for example heart or liver cells. Despite this promise, generation of iPSCs is hampered by low efficiency, especially when using human cells.

"It's a game changer," says Edward Morrisey, PhD, professor in the Departments of Medicine and Cell and Developmental Biology and Scientific Director at the Penn Institute for Regenerative Medicine. “This is the first time we've been able to make induced pluripotent stem cells without the four transcription factors and increase the efficiency by 100-fold.” Morrisey led the study published this week in Cell Stem Cell.

“Generating induced pluripotent stem cells efficiently is paramount for their potential therapeutic use,” noted James Kiley, PhD, director of the National Heart, Lung, and Blood Institute’s Division of Lung Diseases. “This novel study is an important step forward in that direction and it will also advance research on stem cell biology in general.”

Before this procedure, which uses microRNAs instead of the four key transcription factor genes, for every 100,000 adult cells re-programmed, researchers were able to get a small handful of iPSCs, usually less than 20. Using the microRNA-mediated method, they have been able to generate approximately 10,000 induced pluripotent stem cells from every 100,000 adult human cells that they start with. MicroRNAs (miRNAs) are short RNA molecules that bind to complementary sequences on messenger RNAs to silence gene expression.

The Morrisey lab discovered this new approach through studies focusing on the role of microRNAs in lung development. This lab was working on a microRNA cluster called miR302/367, which plays an important role in lung endoderm progenitor development. This same microRNA cluster was reported to be expressed at high levels in embryonic stem cells, and iPSCs and microRNAs have been shown to alter cell phenotypes.

The investigators performed a simple experiment and expressed the microRNAs in mouse fibroblasts and were surprised to observe colonies that looked just like iPSCs.  "We were very surprised that this worked the very first time we did the experiment," says Morrisey.  "We were also surprised that it worked much more efficiently than the transcription factor approach pioneered by Dr. Yamanaka."

Since microRNAs act as repressors of protein expression, it seems likely that they repress the repressors of the four transcription factors and other factors important for maintaining the pluripotent-stem-cell state. However, exactly how the miRNAs work differently compared to the transcription factors in creating iPSCs will require further investigation.

The iPSCs generated by the microRNA method in the Morrisey lab are able to generate most, if not all, tissues in the developing mouse, including germ cells, eggs and sperm. The group is currently working with several collaborators to redifferentiate these iPSCs into cardiomyocytes, hematopoietic cells, and liver hepatocytes.

"We think this method will be very valuable in generating iPSCs from patient samples in a high-throughput manner" says Morrisey. microRNAs can also be introduced into cells using synthetically generated versions of miRNAs called mimics or precursors.  These mimics can be easily introduced into cells at high levels, which should allow for a non-genetic method for efficiently generating iPSCs.

"The upshot is that we hope to be able to produce synthetic microRNAs to transform adult cells into induced pluripotent stem cells, which could eventually then be redifferentiated into other cell types, for example, liver, heart muscle or nerve cells" says Morrisey.

Other authors of the study include Frederick Anokye-Danso, Chinmay M. Trivedi, and Jonathan A. Epstein, all from Penn. These studies were funded by the National Heart, Lung and Blood Institute Progenitor Cell Biology Consortium and Division of Lung Disease and the American Heart Association Jon DeHaan Myogenesis Center Award.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania is recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

 

Wednesday, March 9, 2011 -

Applications for undergraduates and high school seniors are now available!  Click here for details.

Tuesday, March 8, 2011 -

 

For teachers with little to no scientific training, leading science lessons in the classroom can be downright intimidating.  Jamie Shuda—a self-described educator by training and scientist by interest—is making it her goal to demystify science in the classroom for both students and teachers.  For the full interview, click here.

 

Monday, February 7, 2011 -

John Gearhart, IRM Director announces eight new programs. 

Monday, January 10, 2011 -

PHILADELPHIA – Given the amount of angst over male pattern balding, surprisingly little is known about its cause at the cellular level. In a new study, published in the Journal of Clinical Investigation, a team led by George Cotsarelis, MD, chair of the Department of Dermatology and IRM Executive Committee Member has found that stem cells play an unexpected role in explaining what happens in bald scalp.

Using cell samples from men undergoing hair transplants, the team compared follicles from bald scalp and non-bald scalp, and found that bald areas had the same number of stem cells as normal scalp in the same person. However, they did find that another, more mature cell type called a progenitor cell was markedly depleted in the follicles of bald scalp.

Click here to view the full release.

Monday, November 22, 2010 -

John Gearhart, Director of the Penn Institute for Regenerative Medicine talks to Philadelphia Inquirer's Marie McCullough about the federal appeals court decision to take place next month regarding stem cell research.  For the full article, click here.

Thursday, October 21, 2010 -

John Gearhart, PhD, IRM Director, is quoted in a CBS3 story about a new stem cell banking product called C'Elle, which allows women to collect menstrual blood in hopes of the stem cells within the blood one day being used as treatments for diseases from Alzheimer's to cancer. Gearhart called the research behind the service "very preliminary."   Click here for video.

Wednesday, August 25, 2010 -

John Gearhart, PhD, Director of the Institute for Regenerative Medicine, comments in a New York Times article about the complications that have arisen in the field of stem cell biology since its controversial beginnings. Scientists have asked why they can't find a way to unmask all of a cell’s genes and turn it directly into a stem cell without using an embryo? Now researchers are trying to figure out whether stem cells made by a reprogramming process really are the same as ones taken from embryos. Gearhart said some investigators ended up with reprogrammed cells “that will have little utility.” They are only partly reprogrammed, he explains. “One worries about how safe and effective they are going to be” if they are ever used in therapies.   See NY Times for full article. 

Wednesday, August 25, 2010 -

Jonathan Moreno, PhD, David and Lyn Silfen University Professor of Ethics, Department of Medical Ethics and member IRM Internal Advisory Committee was quoted in an Associated Press article reporting on the Obama administration's pending appeal of a judge's ruling that undercuts taxpayer-funded research using human embryonic stem cells. The article appeared in more than 200 print outlets including the Washington Post and the Philadelphia Inquirer.

Monday, August 23, 2010 -

A total of 29 summer internship awardees completed their summer research program in July and August.   Twenty-two undergraduates (Center of Excellence and IRM) completed an eight week internship between June 1st and July 23rd and another seven high school students completed a six-week internship between July 12th and August 20th.  Working in a laboratory is an excellent way to encourage students to attend schools in the sciences, since a positive experience often encourages students to purse this area of investigation.