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Delving Into Autism’s Genetics • The Man Behind A Biological Blockbuster • Hooked on Research • Better Testing for TB • In the Heart of the Action On and Off the Court • In The Eye of A Stormy Debate • Finding Clues To Alzheimer’s Disease • Small Beginnings, Big Outcomes • Seeking Answers in Amniotic Stem Cells • Moving Closer to a Cancer Cure • The Brilliance of Beacons

A Day in the Lab
with Anna Barrett, MD
Stroke causes major long-term disabilities for many. This physician-researcher forges new paths to recovery for those in her care.

The Making of a Researcher
A profession centered in the laboratory is still a magnet for those with a passion for science. We introduce you to 11 top doctoral students at UMDNJ’s Graduate School of Biological Sciences (GSBS) and the Dean and VP who is both their role model and support.

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The Expert Series
Meet the man whose expertise guides laboratory scientists through the maze of patents and licensing.

Faculty Focus
The lowly nematode is a “near-perfect research subject” for Ron Ellis, PhD, an associate professor of molecular biology at UMDNJ-School of Osteopathic Medicine.

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Quick-takes of some of our major research stories.

Alumni Profile
Frederick F. Buechel, Sr, MD, UMDNJ-New Jersey Medical School class of ’72, has more than 150 U.S. and international patents to his name. And he’s not done yet!

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Seeking Answers in Amniotic Stem Cells
words by Mary Ann Littell / photograph by Andrew Hanenberg


DALE WOODBURY, PHD, ASSISTANT PROFESSOR, IRA B. BLACK CENTER FOR STEM CELL RESEARCH, DEPARTMENT OF NEUROSCIENCE AND CELL BIOLOGY, UMDNJ-ROBERT WOOD JOHNSON MEDICAL SCHOOL

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onsider a person with advanced liver disease, ill and jaundiced, perhaps waiting for a liver transplant. Then imagine that a new liver could be grown from the person’s very own cells. This is the vision of regenerative medicine — a vision Dale Woodbury dreams of making a reality.

Regenerative medicine is the process of creating live, functional tissues to repair tissues or organs that have been damaged by age, disease or other degenerative changes. In a sense, the body’s tissues heal themselves and regenerate. Scientists may soon be able to grow organs and tissues outside the body and transplant them.

These experimental therapies are based on stem cells, which have the ability to differentiate into a diverse range of specialized cell types.

Woodbury is fascinated by the potential of special types of stem cells found in extra-embryonic tissues, commonly referred to as the afterbirth. “The amnion surrounds the baby when it’s developing and is discarded after the birth,” he explains. “We think the stem cells in those tissues may be useful in treating such diseases as diabetes, liver disease and bone disorders, including osteoporosis.”

The scientist is a natural explorer in every aspect of his life. He thinks nothing of hopping into the car and driving until he’s west of the Mississippi. Among his favorite spots are some of the national parks. “I highly recommend Utah and Arizona. Zion and Bryce National Parks and the north rim of the Grand Canyon are the most beautiful places in the world.”

Woodbury’s interest in science began early and blossomed in college. “The advent of molecular biology is what motivated me to go to graduate school,” he says. He obtained his undergraduate degree in pathobiology at the University of Connecticut and came to New Jersey and Rutgers for his PhD. There he met up with researcher Bill Moyle, PhD, a professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at UMDNJ-Robert Wood Johnson Medical School (RWJMS), who became his mentor. “Bill’s a genius — one of the smartest people I’ve ever encountered,” Woodbury observes. The two investigated gene regulation, studying a protein involved in making steroids. Using molecular biology techniques, they were able to isolate the promoter of a particular gene and study how it is regulated in different cell lines.

Woodbury arrived at RWJMS in 2000 to run a lab doing stem cell research. He and one of his graduate students, Akiva Marcus, MD, PhD, began their work with rat amnion. When they found stem cells, they decided to see if these same cells could be found in human amnion. Obtaining the afterbirth from a recent delivery, they went to work, but found the amnion hard to handle. “It folds and tears when you try to cut it, so we couldn’t easily take samples,” says the scientist. The two put on their engineering hats and came up with the idea of a hole-punch device that would cut right through the slippery tissue. “It’s the size of a stapler and designed so that not just physicians, but anyone in the delivery room would be able to get samples.”

Woodbury and Marcus, who is currently doing a residency in medicine at New York’s Beth-Israel Hospital, have launched a company to market their products and services and are developing a prototype for the device. They’re currently seeking funding for their work — not an easy task in a struggling economy.

“We’d like to create a bank of amnion-derived stem cells and offer this service to expectant parents, in much the same fashion as banks for babies’ umbilical cord blood,” says Woodbury. Possible applications for amnion-derived stem cells include treating cardiovascular disease, bone and cartilage disorders, and perhaps osteoporosis. “The stem cells in amnion will treat different diseases than the stem cells in cord blood, so it makes sense to store both of them. Also, our research has shown that it is much easier to store pieces of amnion than it is to store cord blood.”

“We believe amniotic stem cells hold great potential,” he says. “And with approximately 41/2 million births in the U.S. each year, there is no shortage of tissue.”

Amnion Stem Cells: Banking for the Future
by Dale Woodbury


A. Human ADSCs can be isolated from amnion tissue samples (left) in explant cultures. B. Isolated ADSCs uniformly express the intermediate filament protein vimentin (red stain).

Stem cell therapy may revolutionize the way we treat disease. Scores of clinical trials investigating stem cell therapies are currently underway in the U.S., yet significant hurdles remain. Future success will require pairing the appropriate stem cell population with the disease being treated and genetically matching stem cell donors to recipients. Stem cell repositories that reflect the genetic diversity of the world population will be required. Work performed at UMDNJ has identified the amnion as an abundant source of stem cells that can be harvested and stored with unrivaled ease. Genetically diverse stem cell banks generated from amnion and other sources will become valuable resources as stem cell therapies advance.

Introduction
Regenerative medicine (RM) represents a novel approach to the treatment of disease. Utilizing diverse approaches such as tissue engineering, bioactive molecules and stem cells, RM seeks to repair or restore damaged tissues and organs. Therapies targeting varied disorders, from diabetes to Parkinson’s disease, have been envisioned. For RM to be successful, appropriate populations of stem cells to treat each disease must be identified. Recent studies have suggested that stem cells found in the extra-embryonic tissues may play a role in future therapies.

The extra-embryonic tissues, comprising the placenta, umbilical cord, amnion and chorion, nurture and protect the fetus during development. When the child is born these tissues, collectively referred to as the afterbirth, have served their purpose and are no longer needed. Historically, the afterbirth has been discarded as medical waste and its valuable stem cell populations lost. The recent development of life-saving therapies based on umbilical cord blood has altered this practice. Expectant parents now have the option of banking their newborn’s cord blood stem cells against the advent of hematological disorders. Stem cells in adjacent tissues, which target diseases cord blood stem cells do not, are rarely saved. As RM matures, these under-appreciated stem cells from the afterbirth will become invaluable. The stem cell that captures the clinic is likely to be the one most easily harvested and stored. In this regard, the stem cells from the amnion have no equal.

Amnion Banking and Amnion-derived Stem Cells
The amnion is an elastic and resilient membrane that completely encircles the developing fetus. The membrane is exceedingly thin, being at most two cell layers deep. This sheet-like structure provides cells in the amnion unfettered access to oxygen and nutrients during harvest, transport and storage of the tissue. As a result, resident stem cells of the amnion can be frozen away within the intact tissue, eliminating the need for extensive processing. No other extra-embryonic stem cell source, including cord blood, is as easy to harvest and store.

The amnion contains multiple stem cell populations. One of these, the amnion-derived stem cells (ADSCs), has been the focus of our studies. ADSCs, initially isolated from the rat, are multipotent. In vitro studies demonstrated differentiation to adipocyte-, osteocyte-, hepatocyte- and neuron-like cells. ADSCs transplanted to the fetal rat brain differentiated primarily to vascular elements. These results suggest that ADSCs may be useful in treating a variety of disorders. Further work will be required to identify their niche in stem cell therapeutics.

Cells with ADSC-like attributes have recently been isolated from human amnion and investigations into their clinical potential are ongoing. Pilot studies performed in collaboration with Dr. Dan Medina (CINJ) have demonstrated that human ADSCs are able to expand cord blood stem cells in the laboratory, potentially increasing the therapeutic value of these banked cells. Isolation of cord blood and amnion from the same afterbirth is technically feasible, and may ultimately prove beneficial.

Intellectual Property
Our work with ADSCs has resulted in the filing of two patent applications through UMDNJ’s Office of Patents and Licensing. The first of these covers aspects of ADSC isolation, therapeutic application of ADSCs and methods of ryopreservation of amnion stem cells. This application is currently pending in the U.S. and E.U.
The second patent application was inspired by difficulties encountered when working with human amnion. Intact amnion is highly elastic and resistant to tearing. However, once compromised the membrane rips easily and unpredictably. As a result, sample isolation utilizing standard surgical instruments is difficult and time consuming.

To overcome these difficulties, an amnion sampling instrument called the AmnioPunchTM has been devised. The hand-held, disposable AmnioPunchTM is designed to harvest amnion samples of reproducible size and deposit them directly into vials for subsequent transport and storage. The AmnioPunchTM allows for rapid amnion sampling in virtually any delivery room, facilitating stem cell banking.

Commercialization
A new firm called Amniochor has been launched to commercialize this exciting technology. The company will compete in two separate but interrelated markets: stem cell banking and stem cell-based therapeutics. The company has an exclusive option to license technologies from UMDNJ that provide competitive advantages in both arenas. With a new CEO on board and savvy investors engaged, AmnioChor is poised to bring these technologies to the marketplace.