McGowan Institute?
March 2006 | VOL. 3 | www.McGowan.pitt.edu
U.S. Senator Rick Santorum announced on March 3, 2006 that $1 million in congressionally directed funding was available for medical research to improve treatment of soldiers wounded in combat. This funding will support the new Soldier Treatment and Regeneration Consortium (STRaC), a national partnership of leading military and academic research centers and industry, including the Pittsburgh Tissue Engineering Initiative and the McGowan Institute. (Pictured right: Senator Santorum, Chancellor Mark Nordenberg and McGowan Institute Director Alan Russell. Picture by Jim Burke.)
STRaC-funded projects will focus on preclinical and clinical regenerative medicine research to engineer functional vascular, nerve and muscle tissue, as well as bone and cartilage, for the creation of digits and limbs. Extremity injuries caused by blast, blunt or penetrating trauma are particularly complex because of these many tissues involved, each with distinct functions. Using regenerative medicine techniques, including tissue engineering and cellular therapies, STRaC researchers will develop partial components as well as entire functional extremities. The five-year goal is the creation of a fully functional digit (finger).
At the announcement, University of Pittsburgh Chancellor Mark Nordenberg introduced Senator Santorum, noting that “This pioneering initiative has the potential to dramatically enhance the power of medicine to help repair damaged lives, even while it advances an increasingly important sector of this region's new technology-driven economy. We are privileged to be a part of this initiative and are grateful to Senator Santorum for his strong support.”
The Senator made the announcement while visiting PTEI and the McGowan Institute for Regenerative Medicine, where he met with a cadre of high-ranking military medical officers who detailed the great need for advanced medical therapies for the horrific wounds caused by conventional weapons and improvised explosive devices. While significant improvements in body armor have greatly increased survivability, the wounded sustain far more serious injuries, including a rate of limb amputation twice as high as Vietnam. Approximately six percent of those wounded in Iraq have required single or multiple amputations.
In addition to PTEI and the McGowan Institute, STRaC partners include the U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas; U.S. Army Medical Research and Materiel Command; the San Antonio, Texas-based TRISAT Trauma Collaborative; Walter Reed Army Medical Center; Regenerative Medicine Foundation; Tissue Genesis, Inc., Honolulu, Hawaii; and the Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina.
The National Cancer Institute in collaboration with the National Institute of Biomedical Imaging and BioEngineering (NIBIB) has funded a three-year study under the leadership of J. Peter Rubin, MD to examine the feasibility of using human preadipocytes, seeded on microcarrier scaffolds, that can be injected into an animal model to produce a durable engineered soft tissue replacement. Human Preadipocytes are derived from human adipose tissue.
Co-investigators on the study include Kacey Marra, PhD, Albert Donnenberg, PhD, and Vera Donnenberg, PhD. Stephen Badylak, DVM, PhD, MD serves as a advisor to the research team.
Breast cancer is endemic in the United States, with nearly 216,000 new cases expected this year (American Cancer Society statistics). For patients undergoing mastectomy, the loss of one or both breasts can cause significant discomfort and psychosocial distress.
The number of breast reconstruction operations exceeds 80,000 cases per year (American Society of Plastic Surgeons statistics). Current surgical options, including autologous tissue flaps and implants, have significant problems. The use of adipose precursor cells, or preadipocytes, may represent a better solution for soft tissue reconstruction for cancer defects.
The study will test the hypothesis that human preadipocytes can be seeded on microcarrier scaffolds and be injected into an animal model to produce a durable engineered soft tissue replacement.
Furthermore, the research team speculates that the preadipocytes will differentiate into both adipocytes and elements of the new vascular system that perfuses the fat tissue.
The specific aims of this study are to:
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Characterize cell surface markers of human preadipocytes using flow cytometry and assess the variability of differentiation of cloned subpopulations. Preadipocytes will be isolated from adipose tissue of breast cancer patients for clinical relevance.
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Evaluate the adherence, proliferation and adipogenic differentiation of human preadipocytes within macroporous collagenous beads and small intestinal submucosa (SIS) microparticles in culture.
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Determine the ability of human preadipocytes to generate mature adipose tissue when seeded in collagen and SIS particles and injected subcutaneously into a mouse model.
Winners of the 2006 chancellor’s awards for distinguished research and public service were announced at the February 24, 2006 University of Pittsburgh honors convocation.
The Chancellor’s Distinguished Research Award recipients included McGowan Institute faculty member Richard Debski who is an assistant professor of bioengineering in the Department of Bioengineering.
Chancellor Nordenberg wrote to Debski that “it is a measure of your intellectual depth that you are widely recognized in the fields of experimental biomechanics, computational biomechanics and robotic technology. This status has been highlighted by the numerous awards that you have received. However, it was formalized when the American Society for Mechanical Engineering awarded you its Y.C. Fung Young Investigator Award, the most prestigious national award that a young scholar in your field can receive.”
David H. Perlmutter, the Vira I. Heinz Professor and chair of pediatrics and professor of cell biology and physiology at the School of Medicine, has been named one of five new members of the advisory council of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
The council advises NIDDK about its research portfolio. The council typically undertakes broad issues of science policy. Perlmutter, who will serve on the NIDDK’s advisory council’s digestive diseases and nutrition subcommittee, also is scientific director of the John G. Rangos Sr. Research Center and physician-in-chief at Children’s Hospital.
Timothy Billiar, a professor of surgery in School of Medicine, will continue research into understanding the key precipitators of organ injury that results from hemorrhagic shock.
A $1.56 million grant from the National Institute of General Medical Sciences will help Billiar’s team characterize the earliest molecular events leading to the initiation and propagation of inflammatory changes following trauma.
Trauma is the leading cause of death in America in people under the age of 54 years. Except for major head injury, hemorrhage and its consequences are the most important causes of morbidity and mortality in these young, otherwise healthy individuals.
The research focus is on a better understanding of the events leading to the activation and propagation of pro-inflammatory and stress signaling pathways that contribute to organ damage and dysfunction after a severely injured trauma victim is resuscitated.
There is a need for materials that can respond automatically to environmental changes and perform a specific function without external intervention. This is particularly important with respect to mechanical damage, where responsive systems could prevent catastrophic failure. There also is a need for lightweight materials that show multifunctional behavior.
New research by McGowan faculty member Anna Balazs professor of chemical engineering professor, in conjunction with researchers from the University of Massachusetts, published February 12, 2006 issue of Nature Materials shows that nanoparticles dispersed in a polymer matrix migrated to cracks at the interface between the polymer and a glassy layer.
The movement, based on the enthalpic and entropic reactions between the polymer and the nanoparticles, shows that nanoparticles may provide a way to make more durable, self-healing systems and may form the basis for materials that can respond to environmental changes.
The research may be helpful in developing stronger materials for components made up of multilayer composites used in optical communications, microelectronics and bioengineering applications.
Antidepressant treatment is the most effective way to prevent recurrence of depression in people over the age of 70, according to School of Medicine research published in the current issue of the New England Journal of Medicine.
Left untreated, 50-80 percent of people in this age group will experience another episode of depression. But researchers found that participants who took the serotonin reuptake inhibitor (SSRI) paroxetine for two years after an initial depressive episode were much less likely to experience a relapse than those who received a placebo.
“By preventing depression in the elderly, we can improve the quality of life significantly in this population,” said David J. Kupfer, professor and chair in the School of Medicine Department of Psychiatry, and co-author of the study. “This study provides evidence that SSRI treatment given for two years can improve the lives of the elderly with major depression and should be the gold standard of treatment for this population.”
The Regenerative Medicine Podcasts continue to be well received. There have been about 1,200 downloads of the five interviews. The podcasts to date as follows:
| Amit Patel, MD-UMPC/McGowan Institute |
| Frederick J. Schoen, MD, PhD-Harvard Medical School and Brigham & Women’s Hospital |
| Stephen Badylak, MD, DVM, PhD-McGowan Institute |
| Alyssa Panitch, PhD-Arizona State University |
| Alan Russell, PhD-McGowan Institute |
Coming on April 1st: Andrés García. Georgia Tech and Tiffany Sellaro-TERMIS-SYIS
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
The 2006 McGowan Institute Retreat was held on March 6 and 7, 2006. The focus was on enhancing our networking with industry, by sharing our capabilities with prospective industrial partners and learning about the needs of industry relative to bringing regenerative medicine technologies to clinical use.
For the 2006 Retreat, 38 key industrial leaders in different industrial sectors related to regenerative medicine participated.
The highlights of the retreat program included:
- Keynote address by Gail Naughton, Ph.D., Dean of College of Business Administration, San Diego State University, and Advanced Tissue Sciences Co-Founder and Vice Chair;
- Overviews of capabilities and interests of McGowan Institute Faculty;
- Introduction of the new and improved pathways to collaborate with and license University of Pittsburgh technologies;
- One-on-one “mini-sessions” between key industry personnel and faculty;
- Definition of industrial needs and development of means for enhanced collaboration;
- Poster session to introduce the focus and interests of Institute faculty (posters from the industrial participants are welcomed but not required);
- Special postdoctoral networking session.
The winners of the poster session were:
Category A: Artificial Organs & Medical Devices & Modeling
First Place Winner:
“3D Expansion of Mouse Embryonic Stem Cells in Four-Compartment Bioreactors”
Mariah S. Hout, Matt J. Baun, Hina Qidwai, Gerald P. Schatten and Jörg C. GerLach
Honorable Mention:
“A Biohybrid Lung Prototype with Active Mixing and Oxygenation of Endothelialized Microporous Hollow Fibers”
Alexa A. Polk, Daniel T. McKeel, Craig Lehocky, William J. Federspiel and William R. Wagner
Category B: Bioengineering and Tissue Engineering
First Place Winner:
“In-vitro Assessment of a Biodegradable Electrospun Vascular Graft Surface-seeded with Muscle-derived Stem Cells and Subjected to Shear Stress”
Lorenzo Soletti, John J. Stankus, Alejandro Nieponice, Jennifer Bacior William R. Wagner and David A. Vorp
Honorable Mention:
“Host Response to Orthopaedic ECM Bioscaffolds”
Jolene E. Valentin and Stephen F. Badylak
Category C: Cellular Therapies
First Place Winner:
“Muscle-Derived Stem Cells Spontaneously Express Neuronal Markers In Vitro and Promote Peripheral Nerve Repair”
M. Lavasani, A. Usas, A. Lu, L. Y. Santiago, J. Cummins and J. Huard
Honorable Mention:
“Functional Repair of Infarcted Hearts Mediated by Skeletal Muscle Stem Cells and Their Secretion of VEGF”
T. R. Payne, H. Oshima, M. Okada, N. Momoi, K. Tobita, B. B. Keller, H. Peng and J. Huard
Publication of the Month
Publication of the Month | March 2006 |
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| Author(s) | Srikanth Ranganathan (1), Eric Williams (2), Philip Ganchev (2), Vanathi Gopalakrishnan (2), David Lacomis (3), Leo Urbinelli (4), Kristyn Newhall (4), Merit E. Cudkowicz (4), Robert H. Brown Jr. (5) and Robert Bowser (1) 1) Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA |
| Title | Proteomic Profiling of Cerebrospinal Fluid Identifies Biomarkers for Amyotrophic Lateral Sclerosis |
| Summary | Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease, affecting one in every 40 000 individuals (Jackson and Bryan 1998). It typically affects individuals in their mid-50s and is characterized by rapidly progressive degeneration of motor neurons in the cerebral cortex, brainstem and spinal cord. The median survival in ALS is three to five years (Jackson and Bryan 1998; Cleveland and Rothstein 2001). ALS exists in both sporadic and familial forms. Familial ALS (FALS) comprises only 5–10% of all ALS cases. Since amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons, the study tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, the research team compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). The investigation identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule-learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy-terminal fragment of neuroendocrine protein 7B2) in ALS CSF. The research team validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS. |
| Source | J. Neurochem. (2005) 95, 1461–1471. |
Grant of the Month
Grant of the Month | March 2006 |
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| PI | J. Peter Rubin, MD; Kacey Marra, PhD; Albert Donnenberg, PhD; Vera Donnenberg, PhD; Stephen Badylak, DVM, PhD, MD |
| Title | Injectable Engineered Tissue for Cancer Reconstruction |
| Description | Breast cancer is endemic in the United States, with nearly 216,000 new cases expected this year (American Cancer Society statistics). For patients undergoing mastectomy, the loss of one or both breasts can cause significant discomfort and psychosocial distress. The number of breast reconstruction operations exceeds 80,000 cases per year (American Society of Plastic Surgeons statistics). Current surgical options, including autologous tissue flaps and implants, have significant problems. The use of adipose precursor cells, or preadipocytes, may represent a better solution for soft tissue reconstruction for cancer defects. The study will test the hypothesis that human preadipocytes can be seeded on microcarrier scaffolds and be injected into an animal model to produce a durable engineered soft tissue replacement. Furthermore, the research team speculates that the preadipocytes will differentiate into both adipocytes and elements of the new vascular system that perfuses the fat tissue. The specific aims of this study are to:
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| Source | RO1: NCI, along with NIBIBRO1: NCI, along with NIBIB |
Term |
3 years |