February 2007 | VOL. 6, NO. 2 | www.McGowan.pitt.edu

The February 12, 2007 issue of the Wall Street Journal (page A1), Ron Winslow highlights the pioneering work of McGowan scientist Stephen Badylak, MD, DVM, PhD. In the 1980s, Dr. Badylak identified the importance of extracellular matrix, which scientists say harbors signaling molecules that help direct the development of cells into tissue, during an experiment in which he used a portion of a dog's intestine to fashion a makeshift aorta for its heart. Not only was the dog's tail wagging the morning after the surgery, but months later, an examination revealed that the transplanted intestine part had morphed into a vessel that looked much like an aorta. Somehow, it had sensed where it was in the body and had remodeled itself to take on the structural traits of an aorta. There was hardly any scarring.

Subsequent research has helped Dr. Badylak and his colleagues understand the mechanisms behind this remarkable tissue remodeling. That research to a layer of intestinal lining called the submucosa, a form of extracellular matrix. Dr. Badylak's team found that extracting the submucosa from the intestine and putting patches of it at injury sites triggered a novel healing response: As the implanted matrix material broke down, healthy living tissue, not scar tissue, repaired the damage. Matrix from bladders, liver and other organs induced a similar reaction.

The matrix, considered a medical device by the Food and Drug Administration, is now commonly used in rotator-cuff procedures and Achilles-tendon repairs. Other orthopedic-products companies have developed similar technology that they market as an alternative or adjunct to conventional orthopedic procedures. Over 1,000,000 patients world-wide have benefited by some form of this matrix.

In 2005 a 68 old hobby shop owner accidentally lopped about three-eighths of an inch off the top of his middle finger on the propeller of a model airplane. A novel treatment was devised using a powdered version of the extracellular matrix which was applied to the end of the severed finger every other day for 10 days; in four weeks, the wound was healed. In four months the finger resembled the original finger prior to the accident.

Using a similar strategy, five soldiers at a Texas military base are about to participate in a remarkable test to see if they can regrow portions of fingers they lost in the war in Iraq.

Doctors plan to treat them with a powdered version of the extracellular matrix, harvested from pig bladders. The experimental procedure is expected to begin late this spring; surgeons will reopen the skin around what's left of the soldiers' fingers. Matrix will be applied three times a week for at least two weeks. During each application, researchers will look for new tissue and for complications. If no problems arise in the first five soldiers, the doctors will treat five more, and then assess the procedure thoroughly. They hope to know within a couple of months after treatment begins whether it works.

MORE

Daniel Bates in the January 29, 2007 issue of the Pitt Chronicle highlights the work of Amber Loree a senior in bioengineering. Amber has been has interned for the past year in laboratories of Professor William Federspiel. Working with Dr. Federspiel and his doctoral student, Kristie Burgess, they are developing and testing small, polymer-based artificial lung modules with tiny pathways for diffusing blood, oxygen, and carbon dioxide.

In this research project the focus is to develop an entirely new technology platform, including fabrication processes, on which to develop artificial lung and other respiratory-assist devices that operate outside of the human body and will work as well as, or perhaps even better than, natural lungs.

Amber has found herself in the middle of this groundbreaking innovation-development effort. Using soft lithography, Loree, Burgess, and Federspiel have managed to fabricate working modules that could be used to assemble a new respiratory device. Eventually, the team hopes to produce a device that will serve as artificial lungs providing long-term gas exchange for patients with deteriorating lungs.

Amber’s professional passion is in artificial organ research and development, and her experience in Dr. Federspiel’s lab has helped to reaffirm that this is her preferred career path.

MORE

McGowan Institute - 2007 Scientific Retreat
Nemacolin Woodlands Resort - Farmington, PA
March 5 and 6, 2007

 

Registration is full. Thanks for registering; look for updates next month.

David A. Vorp, PhD was elected to the board of directors of the Biomedical Engineering Society for a three-year term. Also Dr. Vorp was recently was named to the executive committee of the bioengineering division of the American Society of Mechanical Engineers, to the International Society for Applied Cardiovascular Biology, and to the editorial board of the Journal of Biomechanics.

The Regenerative Medicine Podcasts continue to be well received. There have been nearly 6,500 downloads to date. The most recent podcasts are:

#27- Michael Chancellor, MD
In Podcast 27, we meet Dr. Michael Chancellor , Professor of Urology at the University of Pittsburgh as well as a practicing OBGYN. Within the School of Medicine, he is also the Director of Neurourology and Urinary Incontinence Programs. In addition, Dr. Chancellor is the Director of the Mentored Clinical Scientist Development Program in Urology, a research training program sponsored by the National Institute of Health (NIH).

Dr. Chancellor's research interests include developing a new and novel solution to an age-old problem... urinary incontinence. This is a problem that affects over 17 million in the United States. The adult diaper market is estimated to be a $4 billion dollar a year business!

Clinically, Dr. Chancellor uses all of the available resources to treat urinary incontinence, ranging from exercise, to medication, to injection of collagen, to surgery. The injection of collagen can be effective... but for only short periods.

In collaboration with Dr. Johnny Huard, they have developed a promising alterative approach to the treatment of adult urinary incontinence... the use of the patient's own stem cells that are harvested from the patient's leg muscle. This technology has been licensed and Cook Myosite is managing the ongoing clinical trials.

This novel procedure has been recently tested for safety in humans, and as a result of the positive results, an expanded clinical trial will begin soon to further investigate the effectiveness of this therapy.

#28- Thomas Harris, MD, PhD
Most In Podcast 28, we meet Thomas R. Harris, MD, PhD, the Orrin Henry Ingram Distinguished Professor of Engineering and Professor of Biomedical Engineering, Chemical Engineering and Medicine at Vanderbilt University.  Dr. Harris also serves as chair of Vanderbilt’s Department of Biomedical Engineering. Dr. Harris is a Fellow and past president of the American Institute for Medical and Biological Engineering.

The focus of this podcast is the work of Dr. Harris and his colleagues on the development of learning science and learning technology for bioengineering. Dr. Harris is the Director of the National Science Foundation (NSF) Engineering Research Center in Bioengineering Educational Technologies. The Center is a large, multi-university effort involving Vanderbilt, Northwestern University, the University of Texas and the Harvard/MIT Health Sciences and Technology Program. Its purpose has been to develop a new system for bioengineering education.

Dr. Harris is also widely recognized for his research into the problems of lung circulation with an emphasis on transport phenomena, quantitative physiology, mathematical modeling and instrumentation, Dr. Harris has published more than 230 papers, book chapters, proceedings and abstracts in these fields. His research has been concentrated on the quantitative physiology of the exchange of fluids and solutes in the capillaries of the lung.

Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.

Based on the requests of faculty and graduate students for more and different types of networking sessions, the Moleculart project continues.  Our goal is to have a scientific gathering that fosters networking in a different environment. The next session will be in on April 9, 2007, featuring artist Penny Oliver, wife of Chris Oliver, MD. More

 

Authors:	Manuela Tavian,  Bo Zheng,  Estelle Oberlin, Mihaela Crisan, Bin Sun, Johnny Huard, and Bruno Peault
Title:	The Vascular Wall as a Source of Stem Cells
Summary:	We have characterized the emerging hematopoietic system in the human embryo and fetus. Two embryonic organs, the yolk sac and aorta, support the primary emergence of hematopoietic stem cells (HSCs), but only the latter contributes lymphomyeloid stem cells for definitive, adult-type hematopoiesis. A common feature of intra- and extraembryonic hematopoiesis is that in both locations hematopoietic cells emerge in close vicinity to vascular endothelial cells. We have provided evidence that a population of angiohematopoietic mesodermal stem cells, marked by the expression of flk-1 and the novel BB9/ACE antigen, migrate from the paraaortic splanchnopleura into the ventral part of the aorta, where they give rise to hemogenic endothelial cells and, in turn, hematopoietic cells. HSCs also appear to develop from endothelium in the embryonic liver and fetal bone marrow, albeit at a much lower frequency. This would imply that the organism does not function during its whole life on a stock of hematopoietic stem cells established in the early embryo, as is usually accepted. We next examined whether the vessel wall can contribute stem cells for other cell lineages, primarily in the model of adult skeletal muscle regeneration.  By immunohistochemistry and flow cytometry, we documented the existence in skeletal muscle, besides genuine endothelial and myogenic cells, of a subset of satellite cells that coexpress endothelial cell markers. This suggested the existence of a continuum of differentiation from vascular cells to endothelial cells that was confirmed in long-term culture. The regenerating capacity of these cells expressing both myogenic and endothelial markers is being investigated in skeletal and cardiac muscle, and the results are being compared with those generated by satellite cells. Altogether, these results point to a generalized progenitor potential of a subset of endothelial, or endothelium-like, cells in blood vessel walls, in pre- and postnatal life.
Source:	Ann. N.Y. Acad. Sci. 1044: 41–50 (2005). © 2005 New York Academy of Sciences. doi: 10.1196/annals.1349.006

 

PIs:
Title:	National Tissue Engineering Center (Multiple Awards)
Description:	Regenerative Medicine Approach to the Treatment of Abdominal Compartment Syndrome in a Dog Model PI: Stephen F. Badylak, MD, DVM, PhD Abdominal compartment syndrome (open abdomen) is occurring with increasing incidence in wounded soldiers requiring in-theater “damage-control laparotomy”.  The inability to close the fascia of the abdominal compartment following surgery results in prolonged open abdomen in these patients.  Current methods of closure involve synthetic materials, high rates of infection, high morbidity, and a poor outcome.  The present proposal will evaluate a regenerative medicine approach in which the abdominal wall will be reconstructed with functional musculotendinous tissue by the use of an inductive bioscaffold composed of porcine derived extracellular matrix (ECM).  The study will be conducted in a dog model that mimics the human clinical situation. Signaling and Cellular Strategies of Injectable Biomimetic Matrices for Craniofacial Bone Tissue Engineering PIs: Charles Sfeir, DDS, PhD and Prashant Kumta, PhD This project addresses materials development primarily involving the synthesis and characterization of novel injectable bone cement composites containing nanostructured carriers of signaling molecules and protein, as well as an investigation of the signaling properties of specific mineralized tissue extracellular matrix proteins (ECM) and the isolation and purification of stem cells.  These ECM and stem cells will be incorporated into the newly synthesized injectable bone cement materials to form a novel smart biomimetic matrix, the combination of which will be assessed in an animal model to investigate their potential for craniofacial bone tissue engineering.  Rapid Engineered Autologous Blood Vessels PI: William Wagner, PhD and David Vorp, PhD Currently available grafts for small diameter vascular replacement or bypass are fraught with limitations, especially for soldier care purposes.  It is clear that new alternatives are needed, and it is widely felt that the burgeoning field of tissue engineering will be crucial to the development of these new vascular grafts.  Most vascular tissue engineering approaches rely on some sort of scaffold where cells are incorporated. However, many aspects remain unclear regarding the biomaterial properties of the scaffolds, and the cell source used to populate them. A novel poly (ester urethane) urea elastomeric scaffold has been developed and shown to have great potential for cardiovascular tissue engineering applications. Because of their multipotentiality and availability as an autologous cell source, progenitor cells are considered as the ideal source for tissue engineering. Our preliminary data, where a rapid incorporation of progenitor cells within the bioerodible polymer is achieved through a novel seeding technique, shows that a construct fully-seeded with viable cells can be achieved in a very short period of time. Accordingly, the goal of this project is to develop a novel, bioresorbable scaffold, bulk-seeded with human stem cells, and cultured acutely in-vitro so that an optimal implant is available in a short amount of time.  To this end, we propose two specific aims for this one-year project: Develop a rapidly fabricated, bioerodable polymer-based vascular graft bulk-seeded with human stem cells, and Test the mechanical properties, structure and functionality of the vascular graft from Specific Aim 1following an acute, optimized culture period to determine its readiness for in-vivo implantation for further development into a bio-equivalent vascular substitute.
Source:	National Tissue Engineering Center
Term:

Newsletter Comments or Questions: McGowan@pitt.edu

© Copyright 2009 McGowan Institute for Regenerative Medicine
A program of the University of Pittsburgh and the University of Pittsburgh Medical Center