McGowan Institute?
October 2007 | VOL. 6, NO. 10 | www.McGowan.pitt.edu
Senator Specter Holds News Conference on Regenerative Medicine
U.S. Senator Arlen Specter visited with regenerative medicine scientists from the McGowan Institute as part of his recent press conference at the Pittsburgh Tissue Engineering Initiative (PTEI). Senator Specter announced his support for $1.5 million in federal funding and his continued support for the development of regenerative techniques for the Department of Defense (DOD) to safely and efficiently treat combat-sustained injuries.
PTEI is a collaborative partner with the University of Pittsburgh, the University of Pittsburgh Medical Center and others in the nation's first collaborative organization of universities and health care institutions focused on the field of tissue engineering.
During his tour, Senator Specter experienced firsthand from Drs. Alan Russell, W. P., Andrew Lee, and Thomas Gilbert of McGowan Institute, the scientific efforts and accomplishments of the many researchers supporting DOD regenerative medicine technology. The objectives are to restore hands, fingers, faces, ears, noses, breasts, as well as the long-range goals of regenerating arms, legs, and internal organs.
"It's enormously impressive," said the Senator. The research could help 23,000 injured American soldiers, many of whom suffered "candidly grotesque" injuries in Iraq and Afghanistan.
"It's a marvel," Senator Specter said, "we are making our objective a congressional priority." Even though the bill must still be approved by the full Congress and the President before funding is final, Senator Specter was optimistic stating, "I hope to bring more good news in the future."Read more: Pittsburgh Post-Gazette (10/10/07)Photo credit: Andy Starnes/Pittsburgh Post-Gazette.
The Biomedical Engineering Society recently announced its Class of 2007 Fellows during their annual meeting in Los Angeles, CA. Four of the six newly elected Fellows are McGowan Institute Faculty members! Congratulations are extended to, clockwise from the top:
- William Federspiel, PhD, William Kepler Whiteford Professor of Chemical Engineering, Surgery and Bioengineering at the University of Pittsburgh
- Sanjeev Shroff, PhD, Professor and Gerald E. McGinnis Chair in the Department of Bioengineering, as well as Professor of Medicine at the University of Pittsburgh
- Rory Cooper, PhD, Chair and Professor of Rehabilitation Science and Technology, School of Health and Rehabilitation Sciences, and professor of Bioengineering and Mechanical Engineering at the University of Pittsburgh
- William Wagner, PhD, a Deputy Director at the McGowan Institute for Regenerative Medicine, Professor of Surgery, Bioengineering and Chemical Engineering at the University of Pittsburgh, as well as the Director of Thrombosis Research for the Artificial Heart and Lung Program
Fellow status is awarded to Biomedical Engineering Society (BMES) members who demonstrate exceptional achievements and experience in the field of biomedical engineering and a record of membership and participation in the Society. The nomination criteria included:
- Five or more years of membership in the Society.
- Five or more years of active participation as a biomedical engineer in the private or public sectors.
- A demonstrable record of exceptional achievement and accomplishment in a specific field of interest within biomedical engineering. The achievement and accomplishments can be in research, education, industry, public service, new technology, or clinical practice.
The celebration of the members’ achievements began with public recognition of the Class of 2007 Fellows during the recent BMES Annual Fall Meeting. Future recognition includes the posting of all Fellows on the BMES website as well as publishing the honors bestowed on the Class of 2007 Fellows in an upcoming issue of the BMES Bulletin newsletter.
Congratulations, Drs. Cooper, Federspiel, Shroff, and Wagner!
McGowan Institute's Deputy Director of Cellular Therapeutic Research, Johnny Huard, PhD, has one more commendable designation. Not only is he a University of Pittsburgh Professor in the Departments of Orthopaedic Surgery, Molecular Genetics and Biochemistry/Bioengineering; Director of the Children's Hospital of Pittsburgh and UPMC's Stem Cell Research Center; the Henry J. Mankin Endowed Chair in Orthopaedic Surgery Research; the Associate Director of the Pittsburgh Tissue Engineering Initiative (PTEI); and the co-founder of Cook MyoSite, Inc., he is also the University of Quebec at Rimouski (UQAR) 2007 Prix D'Excellence Award winner.
Dr. Huard received this "award of excellence" from his Canadian alma mater, the UQAR, where he received an undergraduate degree in biology (1988). This award is given annually to one graduate from the UQAR for meeting achievements in a chosen career field, demonstrating community involvement, and displaying the ability to share human and ethical values. The impact of his research work—to repair, replace, rebuild, and regenerate damaged or diseased tissue of the musculoskeletal system—has catapulted Dr. Huard into the role of one of the leading scientists in the field of regenerative medicine and research on stem cells.
Dr. Huard received his award in Canada from the Rector of the UQAR, Michel Ringuet, and the president of the Alumni Association, Mr. Alain Couette.
Photograph: UQAR.
Read more: UQAR News Bureau
The 2008 McGowan Institute Scientific Retreat is scheduled for March 10, 11, and 12, 2008 at the Nemacolin Woodlands Resort. The program committee is led by Dr. William Wagner. On-line registration will be available in December, but in the interim, remember to save the dates: March 10, 11, and 12, 2008 (note: 3 days vs. the traditional 2 day format)
The program will include distinguished guest speakers, a poster session, and potential external partners and collaborators, so there will be multiple opportunities for networking and collaboration.
McGowan Institute for Regenerative Medicine faculty members are part of the team of collaborators receiving $4.75 million from the U.S. Department of Education's National Institute on Disability and Rehabilitation Research. The grant to the University of Pittsburgh is to create the Rehabilitation Engineering Research Center (RERC) on Spinal Cord Injury. Others on the RERC team include the Department of Rehabilitation Science and Technology (RST), the Department of Physical Medicine and Rehabilitation, and the Department of Occupational Therapy at the University of Pittsburgh. Other participants are Case Western Reserve University, Northwestern University, Baylor College of Medicine, IBM, and Immunetrics. David M. Brienza, PhD, McGowan faculty member and RST professor at Pitt, will serve as director of the RERC.
Several McGowan Institute faculty members are advisors to Immunetrics, which was founded by Timothy R. Billiar, M.D., Gilles Clermont, M.D., Mitchell Fink, M.D., and Yoram Vodovotz, Ph.D.
Spinal cord injuries result in a particularly debilitating array of conditions that compromise mobility, accessibility, social interactions, employment, and other important dimensions of life. The RERC will research, develop, and evaluate innovative technologies and approaches to improve the treatment, rehabilitation, employment, and reintegration into society of people with spinal cord injuries.
One critical focus of the RERC's research will be to create mathematical models of inflammation and healing, which can vary extensively among individuals. "We believe that the occurrence of pressure ulcers, urinary tract infection, and musculoskeletal injuries that stem from spinal cord injury can be attributed to systemic inflammation," said Dr. Brienza. "We also believe that it is necessary to understand and be able to predict responses to inflammation in order to develop novel, patient-specific therapies for spinal cord injury."
University of Pittsburgh faculty from the departments of surgery and critical care medicine, partnering with researchers from the University of Pittsburgh School of Health and Rehabilitation Sciences, have pioneered a computational approach to develop and calibrate models of the inflammatory process. "We now have four substantial grants that are based on computational simulation and modeling inflammation," noted Clifford E. Brubaker, PhD, dean of the School of Health and Rehabilitation Sciences. "I believe that this research will have important and pervasive influences on the formulation of new therapeutic procedures and the practice of rehabilitation."
The Department of Rehabilitation Science and Technology (RST) was established within the School of Health and Rehabilitation Sciences at the University of Pittsburgh in 1994. RST was created to provide leadership in research, education and clinical practice related to the rehabilitation of individuals with disabilities. Read more: UPMC News Bureau
University of Pittsburgh’s Robert Bowser, PhD (also a McGowan Institute faculty member), and Ronald Hamilton, MD, were part of a joint regenerative medicine research effort that identified a molecular signature common to both familial and sporadic cases of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. The finding reveals that a peptide found in a gene in spinal cord fluid is common to patients with the disease. The work was done through a collaboration of University at Buffalo (UB) chemists with scientists studying ALS at California Pacific Medical Center Research Institute, The Johns Hopkins University, University of California at San Diego, and Pitt.
Researchers at California Pacific (led by Vishwanath R Lingappa, PhD) found an unknown protein species in nanogram quantities (a billionth of a gram) in spinal cord fluid samples from ALS patients. At such low quantities, Troy Wood, PhD, associate professor of chemistry in UB's College of Arts and Sciences, explained, “the standard analytical chemistry technologies are of no use.”
"Only nanotechnology is capable of identifying a species in these amounts," he continued. "Because of the minute amounts of analyte that are present in some samples, nanospray technologies, in particular, which reveal what we call a peptide's mass 'fingerprint,' have emerged as one of the most important tools in the field of proteomics."
In the ALS research, the UB researchers used trypsin, an enzyme, to digest or break down the unknown analyte into small peptide pieces that constitute the "fingerprint," which, in turn, allows researchers to identify the species through mass spectrometry. Through a nanospray emitter, it was found that the unique, cross-linked species contained superoxide dismutase, a protein that had been previously linked to only the familial form of ALS. This peptide provides researchers with an important piece of information as to where to focus future research.
In addition to Bowser, Hamilton, Wood, and Lingappa, other co-authors on the paper recently published in Proc Natl Acad Sci USA, September 2007, are WL Wood, E Alpert, DW Cleveland, A Gruzman, MD Prasad, RG Miller, JD Rothstein and lead author J Liu. Read more: PhysOrg (09/04/07)
UPMC and Baxter Healthcare Corp. are currently partnered in a regenerative medicine clinical trial to study whether a patient's own stem cells can be used to treat severe coronary artery disease. The McGowan Institute's Dr. Joon Sup Lee heads the CD34+ stem cell trial being conducted at UPMC-Presbyterian Hospital.
There are 29 patients participating in the study. One participant, Hugh Rawson of Brownsville, has a history of 4 heart attacks, 24 hospitalizations, 34 heart catheterizations, about 25 stents, and 2 triple bypass surgeries. All of this occurred from 2001-2005. Since his discharge from the hospital in 2005, Rawson has been treated for a variety of ailments, including debilitating and persistent chest pain, but no further heart attacks. When he heard about it, Mr. Rawson jumped at the chance to volunteer for the CD34+ stem cell trial.
"Hugh is at one end of the spectrum. He's certainly had more procedures than our average person in a study like this," said Dr. Lee. "This study is looking at finding a way to improve the quality of life for these patients by growing new arteries to the heart."
Stem cells were collected from Rawson's white blood cells, concentrated, and if a placebo is not being used, reinserted directly into the areas of his heart that had reduced blood flow by using a heart catheterization technique.
Lee said there shouldn't be any adverse affects to the participants in the study due to the fact that only the patient's own stem cells are used. "There's no foreign material that's being injected back in the patient, so there's no chance of rejection," Lee said.
Human trials of medical treatments such as this are vital to the development of effective therapies. "Our field is seemingly filled with therapies that appear effective in animals, but are ineffective in humans," Lee said. "Without people like Hugh, we aren't going to be able to develop new therapies. In animal studies, we make sure the animals have no other medical problems. Our patients aren't like that. Many of them have diabetes or high blood pressure. The type of thing that he has volunteered for is essential in moving the field forward." Read more: UPMC Press Release
A 17-year-old who suffered from a congenital kidney and liver disorder known as autosomal recessive polycystic kidney disease (ARPKD) is the second patient at Children's Hospital in Pittsburgh to undergo a live donor liver-kidney transplant.
The organs were donated by the child's father and maternal grandmother. The boy's father donated a portion of his liver, and the grandmother gave a kidney. The surgeon, Dr. George V. Mazariegos, director of pediatric transplantation at Children's and McGowan faculty member, reported that all three patients were recovering well. Immunosuppressant medication can be kept to a minimum for the transplant patient—another advantage of living donor transplants. In fact, up to ten percent of these transplant patients can have immunosuppressants completely withdrawn from their treatment regimen at some point.
The transplant should cure the patient of the disease (ARPKD) he was born with. ARPKD is rare and often fatal.It occurs only about once in every 20,000 births. The diagnosis is usually made at birth or in early infancy. By the time this transplant patient was one month old, he had both kidneys removed and was undergoing dialysis.
Living donors—almost always family member—give the patient the advantage of avoiding a long waiting list for deceased-donor organs and receiving organs that more closely match. Dr. Mazariegos and his team have worked with ten live donors this year, about one-third of the team's total transplant cases. "The results of the [live donor] adult-to-children [transplants] have been exceptional," Dr. Mazariegos said. Read more: Pittsburgh Post-Gazette
McGowan Institute clinical faculty member Peter Wearden, MD, PhD, is performing life-saving procedures in an experimental program to assess an artificial heart pump for children. He recently led a surgical team involved in the successful clinical trial of the Berlin Heart. The Berlin Heart is an experimental, child-size artificial heart pump—or ventricular assist device (VAD)—that keeps children in life-threatening heart failure alive while awaiting a heart transplant.
For years, VADs have been used successfully for adults awaiting transplants, but only recently have U.S. researchers focused attention on devices for the tiniest heart patients. At UPMC Children's Hospital of Pittsburgh, surgeons have been working with a European VAD called the Berlin Heart. So far, the device has been implanted in five patients, all of whom went on to receive a successful transplant.
Dr. Wearden explains how the device works. "It basically assists the heart," Dr. Wearden told The Pittsburgh Channel. "The blood goes into a sack, and then that sack is forced by air to cause an ejection of that blood, so it sort of replaces what the ventricle of the heart would do."
Currently, the Berlin Heart is the only heart-assist device available for babies and children. Although the FDA has granted compassionate use of the Berlin Heart for children in life-threatening heart failure, the U.S. Food and Drug Administration requires the device to be used on at least 100 patients before it considers approval on a routine clinical basis. In addition to Children's Hospital of Pittsburgh, there are five other centers across the U.S. involved in the clinical trial of the Berlin Heart. Read more: The Pittsburgh Channel
Illustration: MedGadget.
McGowan Institute clinical faculty member Raphael Hirsch, MD, Division Chief of Rheumatology and the Director of the Pediatrics Rheumatology Training Program at Children's Hospital, is assessing joint inflammation in patients using new, high-tech cameras. In his research, thermal cameras are evaluating the pattern of the skin's temperature, searching for hotspots that can appear around an arthritis patient's joints. A second camera is being used to take 3-D snapshots of the body so doctors can more accurately visualize the condition of joints.
"[Traditionally] we assess a patient in a very subjective way," said Dr. Hirsch, also a Professor in the Department of Molecular Genetics/ Biochemistry at the University of Pittsburgh School of Medicine. "[Patients] come in, we look at their joints and try to determine if they are abnormal." When diagnosing Juvenile Rheumatoid Arthritis (JRA), Dr. Hirsch says he looks for the four cardinal signs of inflammation: redness, warmth, swelling, and pain. Unfortunately, these symptoms can be difficult to diagnose in children. "Swelling can be a challenge in an 18-month old because they've got a lot of baby fat," he says. ";Warmth is also difficult, because it's hard to get an accurate assessment by just using your hand." According to Dr. Hirsch, MRIs and X-rays can be used to diagnose JRA, but MRIs aren't routine since they require the child to be sedated, and X-rays will only show arthritis is present once damage has already been done to the bone.
"Normally, the joints are cooler than their surrounding skin, because it's bone," Dr. Hirsch stated. "There is less muscle there, whereas if you have arthritis, you get an inversion of that. The joints actually become warmer than the surrounding skin." Three-dimensional cameras are also being used to take detailed pictures of the joints that help doctors assess swelling. "We are now in the process of validating this through some research studies on patients," says Dr. Hirsch. "The idea would be, this could go into the doctor's office and become part of the routine way a patient is evaluated."
"Today, we have some very good medications," he says. "If you can catch these patients early, you can prevent some of the long term damage to the joints."
Read more: http://www.wftv.com/health/13426076/detail.html
Dr. Anthony Delitto, chair of the Department of Physical Therapy in the School of Health and Rehabilitation Sciences, is the first Pitt faculty member to receive the Mary McMillan Award from the American Physical Therapy Association (APTA). The award is given to acknowledge and honor a member of the APTA who has made a significant contribution to the profession and to provide the recipient with an opportunity to share his or her distinguished achievements and ideas with members through a lecture presented at the association’s annual conference. Delitto will address the June 2008 APTA conference being held at San Antonio, TX.
Michael L. Boninger, M.D., McGowan Institute faculty member, professor of physical and medical rehabilitation, and associate dean for medical student research in Pitt’s School of Medicine has received the eighth annual Ben L. Boynton, M.D. Lectureship. This honor is given through the Department of Physical Medicine and Rehabilitation at the Northwestern University Feinberg School of Medicine. Dr. Boninger has a degree in mechanical engineering in addition to the M.D. he earned at Ohio State University.
The Science2007 exhibition and lecture series that was held from October 11-12, 2007 in Alumni Hall featured a regenerative medicine panel discussion led by William R. Wagner, Ph.D. of McGowan Institute. Other participants were Gerald P. Schatten, Ph.D., Director of the Division of Developmental and Regenerative Medicine, University of Pittsburgh School of Medicine, McGowan Director Alan J. Russell, Ph.D., discussing the science of Dr. Stephen Badylak’s lab, and Constance R, Chu, M.D. speaking about regenerating articular cartilage. The McGowan Institute also participated in Science2007, the theme of which was Collaborate, Innovate, Transform, by having a booth featuring literature and promotional items. The events were well attended, not only by the academic community, but also by the general public.
Pitt faculty, staff and students are increasingly looking for ways to market their technological innovations. Invention disclosures, the first step in the technology transfer process, were up nearly 50 percent in the Office of Technology Management's (OTM) 2007 annual report. The OTM will work to market the technologies and get them to industry.
Technology transfer—the process of bringing a University-developed idea to market—typically involves three major steps: invention disclosure; patenting; then licensing the rights to the innovation for commercial development.
About 80 percent of the FY07 disclosures came from health-related schools, but it should be noted that collaborations are the rule rather than the exception. Most of the disclosures involved multiple inventors and inventions with health/medical applications as well as bioengineering or chemistry input.
Two Pitt startups this past year that include McGowan Institute faculty members are:
Innovation Technologies - Based on a method and system that provides a functional exclusion of the left atrial appendage in cardiac surgery. Developed by Dr. Marco Zenati (cardiac surgery), Dr. David Schwartzman of the School of Medicine, Dr. Mark Gartner (bioengineering) and Daniel McKeel of the McGowan Institute for Regenerative Medicine.
iNTELOMED - Based on several Pitt-developed technologies aimed at noninvasive cardiovascular monitoring and treatment following cardiac trauma. Researchers included Dr. Michael Pinsky of critical care medicine and Dr. Juan-Carlos Puyana of critical care medicine and surgery, both of whom are McGowan faculty members. Read more
The Regenerative Medicine Podcasts continue to attract listeners. The most recent podcasts address topics in regenerative medicine and other pertinent issues such as product licensing and business development.
#40-David S. Smith - Pepper Hamilton LLP David S. Smith is a corporate lawyer who helps scientists transform their work from laboratory investigations into clinical products. In this podcast, Attorney Smith shares his insights on the essential items for early stage companies and business development strategies.
#41-David Vorp, PhD - McGowan Institute for Regenerative Medicine Dr. Vorp introduces his innovative approaches to treat vascular disease and shares the status of these emerging technologies.
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
Authors: |
Qi Mi; Beatrice Rivie`; Gilles Clermont; David L. Steed; Yoram Vodovotz |
Title: |
Agent-based model of inflammation and wound healing: insights into diabetic foot ulcer pathology and the role of transforming growth factor-b1 |
Summary: |
Inflammation and wound healing are inextricably linked and complex processes, and are deranged in the setting of chronic, nonhealing diabetic foot ulcers (DFU). An ideal therapy for DFU should both suppress excessive inflammation while enhancing healing. We reasoned that biological simulation would clarify mechanisms and help refine therapeutic approaches to DFU. We developed an agent-based model (ABM) capable of reproducing qualitatively much of the literature data on skin wound healing, including changes in relevant cell populations (macrophages, neutrophils, fibroblasts) and their key effector cytokines (tumor necrosis factor-a [TNF], interleukin [IL]-1b, IL-10, and transforming growth factor [TGF]-b1). In this simulation, a normal healing response results in tissue damage that first increases (due to wound-induced inflammation) and then decreases as the collagen levels increase. Studies by others suggest that diabetes and DFU are characterized by elevated TNF and reduced TGF-b1, although which of these changes is a cause and which one is an effect is unclear. Accordingly, we simulated the genesis of DFU in two ways, either by (1) increasing the rate of TNF production fourfold or (2) by decreasing the rate of TGF-b1 production 67% based on prior literature. Both manipulations resulted in increased inflammation (elevated neutrophils, TNF, and tissue damage) and delayed healing (reduced TGF-b1 and collagen). Our ABM reproduced the therapeutic effect of platelet-derived growth factor/platelet releasate treatment as well as DFU debridement. We next simulated the expected effect of administering (1) a neutralizing anti-TNF antibody, (2) an agent that would increase the activation of endogenous latent TGF-b1, or (3) latent TGF-b1 (which has a longer half-life than active TGF-b1), and found that these therapies would have similar effects regardless of the initial assumption of the derangement that underlies DFU (elevated TNF vs. reduced TGF-b1). In silico methods may elucidate mechanisms of and suggest therapies for aberrant skin healing. |
Source: |
Wound Repair and Regeneration (2007) 15 671-682 |
PIs: |
Michael S. Sacks, Ph.D. |
| Co-PIs: | Dr. Joyce Bischoff, Dr. David Brown, Dr. Danielle Gottlieb, Dr. John Mayer, Dr. Robert Padera, Dr. Andrew Powell, Dr. Virna Sales, Dr. Frederick Schoen, Dr. George Stetten |
Title: |
Mechanisms of In-Vivo Remodeling in Tissue Engineered Heart Valves |
Description: |
Using autologous cells and biodegradable polymers, tissue engineered pulmonary valves (TEPV) have been fabricated and have functioned in the pulmonary circulation of growing lambs for up to 20 weeks, with tissue evolving into a differentiated layered structure resembling that of native valve. More recent studies have demonstrated that use of bone marrow mesenchymal stem cells (BMSC) and PGH/PLLA scaffolds produce functioning implants for up to 8 months in growing lambs which also demonstrated in-vivo structural evolution. These studies have demonstrated the feasibility of engineering pulmonary valve (PV) leaflets and segments of main pulmonary artery (PA) in-vitro. Both stuctures have functioned well without thrombosis. Moreover, both the gross and microscopic characteristics of the TEPV structures began to approximate those of normal tissues, strongly suggesting that cell phenotypes evolved in a directed fashion to remodel the valvular and vascular tissue. The goal of the current research program is to quantify and simulate tissue remodeling events that occur post-implantation, and to understand the factors that influence the remodeling rate and the quality and architecture of the ultimate tissue. Specifically, we hypothesize that TEPV implant remodeling is primarily mediated by the level of in-vivo mechanical stimuli to the interstitial cells and developing ECM. Mechanical stimuli will affect the rate of scaffold degradation and the degree of post-implant cellular ingrowth. |
Source: |
NIH-National Heart, Lung and Blood Institute |
Term: |
4 years |
Amount: |
$3.3 million |
Newsletter Comments or Questions: McGowan@pitt.edu
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