Co-Investigators Jörg Gerlach,MD, PhD and Jack Patzer, PhD
Title Long-term immunosuppression-free survival of a combined composite tissue allograft (CTA) and autologous skin in a swine model
Grant of the Month
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2009 | August 1, 2009
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2009 | July 1, 2009
Co-Investigators Thomas Gilbert
Title Mechanobiology and Regenerative Medicine
Description Regenerative medicine approaches for the reconstitution of missing or injured tissues and organs involves the use of scaffolds, cells, and bioactive molecules. The use of biologic scaffolds seeded with cells is a common approach and several applications have been successfully translated to clinical medicine including lower urinary tract, gastrointestinal tract, musculotendinous, and dermal skin regeneration. The principles that guide tissue remodeling and regeneration are only partially understood but the influence of biomechanical loading upon the remodeling process is accepted as an important variable. However, there is an almost complete absence of systematic, quantitative studies to determine the effect of this controllable factor upon tissue remodeling, especially tissues with a smooth muscle wall component.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2009 | June 1, 2009
Title Temporal Delivery of Growth Factors for Wound Healing Using Porous Hollow Fibers
Description Our objective is to optimize wound healing through temporal delivery of growth factors using porous hollow fibers extending into a wound site. As an extension to the wound-cap technology (artificial capillary bed delivery system), these fibers can be made from materials that dissolve in the presence of a chemical or temperature-based trigger following the wound healing process. Because angiogenesis is, in many cases, one of the first steps towards wound healing, we propose to demonstrate enablement of this technology by mimicking the natural sequence of stimuli that directs angiogenesis. Our hypothesis is that sequential delivery of appropriate angiogenesis-promoting factors from our externally-regulated delivery system, as opposed to simultaneous delivery of multiple factors, will result in more mature and integrated neo-vasculature.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2009 | May 1, 2009
Co-Investigators Kimimasa Tobita, MD, PhD and Stephen Badylak, DVM, MD, PhD
Title Cardiac Remodeling with Organ Specific Extracellular Matrix Scaffolds
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2009 | April 1, 2009
Title Tissue Engineered Skeletal Muscle (TESM) from Muscle Progenitor Cells: A Model for Studying Insulin Resistance and Muscle Metabolism
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2009 | March 1, 2009
Co. Investigator: Robert Carithers, Adrian Di Bisceglie, Michael Fried, Marc Ghany, Steven Han, E. Jenny Heathcote, W. Ray Kim, Daryl Lau, William Lee, Anna Lok, Mitchell Shiffman, KathleenSchwarz, and Norah Terrault
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2009 | February 1, 2009
Title: Regenerative Medicine Approach to the Treatment of Abdominal Compartment Syndrome in a Dog Model
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2009 | January 1, 2009
Co. Investigator: Sharon Marx and Gabriel Amitai
Title: Temperature responsive modification of microfiber tissue perfusion devices.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | December 1, 2008
Co-PIs: Marina Kameneva, William Wagner, Jörg Gerlach, Mark Yazer
Title: Large Scale Human Placenta Progenitor Cell-Derived Erythrocyte Production – Continuous Red Blood Cell Production
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | November 1, 2008
Co-PIs: Eric Lagasse, William Saunders, and Youjun Li
Title: Function of a Glycoprotein Ibα, a Subunit of the Von Willebrand’s Factor Receptor as a Transforming Oncoprotein
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | October 1, 2008
Co-PIs: Alan Russell, PhD and William Wagner, PhD
Title: Percutaneous Respiratory Assist Catheter
Description: Each year several hundred thousand Americans suffer short term lung failure requiring respiratory support within the intensive care unit. The objective of this proposal is to develop a percutaneous respiratory assist catheter (PRAC) that can be inserted into the venous system to provide supplemental breathing support, independent of the lungs, for patients requiring short-term (~ 4-7 day) respiratory assistance.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | September 1, 2008
Co-PIs: Gregory M. Constantine, PhD (Pitt—Mathematics); Steve Chang (CEO of Immunetrics); Drs. Gary Nieman and Kris Maier (SUNY-Syracuse)
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | August 1, 2008
Co-PIs: William Wagner, PhD
Title: Engineered Early Embryonic Cardiac Tissue
Description: We have developed an Engineered Early Embryonic Cardiac Tissue, termed EEECT, using embryonic cardiac cells isolated during the period of primary morphogenesis in order to investigate the regulation of embryonic CM proliferation and differentiation and to generate tissues with optimal properties for cardiac repair. Our EEECT construct uses a simple cylindrical geometry which is reproducible, scalable, and preserves the unique proliferative and contractile properties of developing myocardium. Using EEECT we can investigate the regulation of CM proliferation and maturation within a functioning in vitro 3D environment. EEECT proliferation and force production increases in response to cyclic mechanical stretch. With prolonged culture EEECT acquires a post-natal myocardial phenotype (reduced proliferation, increased calcium and β-adrenergic sensitivity, and increased force production). Preliminary data show that cylindrical EEECT can be implanted onto recipient injured adult myocardium as part of a cardiac repair/recovery strategy. Implanted EEECT survive, proliferate, and functionally contribute to recipient cardiac functional recovery.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | July 1, 2008
Title Research Training Group Award
Summary Will provide resources to develop training programs for mathematics students to work with physicians and biologists to help resolve complicated medical problems through mathematics. A variety of computer models will be produced based on differential equations to create immune system models to plot the various chemical and physical changes that occur as the body battles influenza, inflammation, sepsis, necrosis, and wounds. The researchers hope to be able to plot and pinpoint the origin of uncontrollable inflammation and infection that can occur as complications following surgery.
Source
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | June 1, 2008
Title Four Projects Funded by CR Bard, Inc.
Summary In vivo and in vitro evaluation of porcine dermal product for pelvic floor and body wall (hernia) reconstruction. ($90,000)
Manufacturing process review and modification. ($96,000)
In vitro characterization of porcine dermis ECM and products in development. ($118,000)
Evaluation of gel form of porcine dermal matrix. ($60,130)
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | May 1, 2008
Title Function of a Glycoprotein lba, a Subunit of the von Willebrand’s Factor Receptor as a Transforming Oncoprotein
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | March 1, 2008
Co-PI(s) Joerg Gerlach
Title Ovarian Cancer, Stem Cells and Bioreactors
Summary Addressing the needs of new approaches for anti-cancer therapies by combining stem cell biology, cancer biology and bioengineering. Our central hypothesis is that cancer stem cells are initiating and sustaining the growth of ovarian cancer. In consequence, the identification of the cancer stem cells represents a major step forward in the elucidation of ovarian cancer hierarchy and could hold the key to understanding the origin and maintenance of ovarian cancer, the relapses and possibly the metastases in advanced cases. Another problem facing cancer cell biology is the access of in vitro culture models for research and study of cancer development and its pathophysiology. Here we propose to adopt bioreactors used for bioartificial livers (BAL) to provide tumor cells with a 3-D perfusion culture instrument that recapitulate vasculature and microenvironment.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | March 1, 2008
Title Armed Forces Institute for Regenerative Medicine
Summary The University of Pittsburgh’s McGowan Institute for Regenerative Medicine and the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center have been selected as co-leaders of a national $85 million program to use the science of regenerative medicine to develop new treatments for wounded soldiers.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | February 1, 2008
Title Advanced Regenerative Medicine (ARM) Therapies for Combat Injuries
Summary Badylak: Digit regeneration using porcine derived scaffolds
Gerlach: Wound cap for tissue regeneration
Gerlach: Skin gun for burn therapy
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2008 | January 1, 2008
Title Levitronix Phase II SBIR
Summary Development of a magnetically levitated, bearingless pump for a pediatric ventricular assist device.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | December 1, 2007
Title: Cardiopulmonary Organ Engineering
Description: Researchers are currently working to develop tissue constructs that could be utilized to repair congenital heart defects and to recover function lost to myocardial infarction. The general approach involves optimizing the combination of precursor cells with synthetic scaffolds and culturing methods to achieve the functionality required for the given application. The research team working on this project includes cardiothoracic surgeons, bioengineers, polymer chemists, cell biologists and electrophysiologists.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | November 1, 2007
Title: Beta-catenin in the growth of hepatocellular cancer
Description: Hepatocellular cancer (HCC) is a disease of poor prognosis. Identifying novel molecular aberrations might present opportunities to identify new therapeutic targets. Due to the similarities between the processes of development and cancer, we used early developing livers to identify genes that might play a primary role in HCC. Platelet-derived growth factor receptor-alpha (PDGFRalpha) was identified from microarray using early developing mouse livers. Expression of PDGFRalpha and its upstream effectors, PDGF-AA and PDGF-CC, were examined in HCC tissues (n = 43) by Western blot, real-time PCR, and immunohistochemistry. Finally, effect of anti-PDGFRalpha antibody (mAb 3G3, ImClone Systems, Inc.) was examined on human hepatoma cells. A high expression of PDGFRalpha was observed during early liver development. HCCs (17 of 21) revealed cytoplasmic PDGFRalpha and activated PDGFRalpha (phospho-Tyr(754)) by immunohistochemistry. Additional HCCs (14 of 22) showed elevated PDGFRalpha levels when compared with the adjacent normal livers by Western blots. Of these 14 patients, 3 showed increased PDGFRalpha gene expression, 3 showed elevated PDGF-AA, and 4 had higher PDGF-CC levels in the tumors compared with adjacent livers. Multiple hepatoma cell lines, when treated with mAb 3G3, showed significant decreases in cell proliferation and survival (P < 0.05). In conclusion, approximately 70% of HCC tissues had elevated PDGFRalpha levels due to diverse mechanisms. PDGFRalpha inhibition in hepatoma cells led to diminution of tumor cell survival and proliferation and thus might be of therapeutic significance.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | October 1, 2007
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
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | September 1, 2007
Co-PIs: Stephen Grant and Michael Epperly
Title: Biomarkers of invasiveness using isogenic and progressive human ductal carcinoma in situ cell lines
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | August 1, 2007
Co-PIs: Douglas Weber, PhD
Title: Surface Modified Polymer Conduits for Peripheral Nerve Repair
Description: The project seeks to increase the understanding of the effects of biomaterial surface properties on nerve regeneration, and also to enhance the integrated research and education activities of graduate, undergraduate and pre-college students. The plan includes outreach programs and innovative research in the exciting areas of biomaterials and tissue engineering. Specifically, the research plan is focused on developing biodegradable conduits with modified inner luminal surfaces that enhance peripheral nerve repair over long gaps, and the educational plan is focused on enhancing and maintaining the involvement of women and underrepresented minorities in engineering.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | July 1, 2007
Co-PI(s) Susan Braunhut, Ph.D., professor of biological sciences at the University of Massachusetts at Lowell
Lorraine Gudas, Ph.D., chairman of the pharmacology department and Revlon Pharmaceutical Professor of Pharmacology and Toxicology, Weill Medical College of Cornell University, New York City
Ellen Heber-Katz, Ph.D., professor, molecular and cellular oncogenesis program, The Wistar Institute in Philadelphia
Shannon Odelberg, Ph.D., assistant professor, departments of internal medicine and neurobiology and anatomy, University of Utah, Salt Lake City
Hans-Georg Simon, Ph.D., a developmental biologist and assistant professor of pediatrics, Children’s Memorial Research Center and Northwestern University in Chicago
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | June 1, 2007
Title “Quantitative proteomics of nuclear matrix proteins in novel human ductal carcinoma in situ model systems”
Summary Background: Ductal carcinoma in situ (DCIS) is the earliest identifiable breast cancer lesion. Because DCIS is a pre-invasive malignancy, a better understanding of if and how it may progress to invasive disease will allow determination of which patients to treat aggressively and avoid unnecessary aggressive procedures. Once determined, these differentially expressed proteins may be used as biomarkers or therapeutic targets, as well as help determine the paths by which normal cells progress to DCIS plus provide a better understanding of breast carcinogenesis and ways to prevent it. Tumor grade, size and presence of necrosis are currently used to make clinical decisions regarding DCIS.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | May 1, 2007
Title Biomechanical Soldier Treatment and Regeneration Consortium (STRaC): Preclinical Study to evaluate the use of UBM-ECM for Partial Thickness Skin Wounds
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | April 1, 2007
Co-PI(s) William Wagner, PhD
Title Biomechanical Optimization of Tissue Engineered Heart Valves
Summary The focus of this competitive renewal grant is a comprehensive biomechanical evaluation of the in-vitro phase of engineered tissue heart valve development.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | March 1, 2007
Co-PI(s) Donald M. Yealy, M.D and Mitchell P. Fink, M.D.
Title Protocolized Care for Early Septic Shock (ProCESS)
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | February 1, 2007
Title National Tissue Engineering Center (Multiple Awards)
Summary Regenerative Medicine Approach to the Treatment of Abdominal Compartment Syndrome in a Dog Model
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2007 | January 1, 2007
Title Biological Markers of Recovery for the Kidney (BioMaRK)
Summary Investigate the role of inflammation, as well as other factors in recovery from acute renal failure (ARF). This project, called Biological Markers of Recovery for the Kidney, or BioMaRK, will examine how such factors influence survival as well as recovery of kidney function. The study will assess how certain inflammation markers relate to clinical outcomes and build a risk-prediction model based on clinical variables and those biomarkers. The results of this study could potentially lay the foundation for the development of ARF treatment therapies, particularly those designed to enhance organ recovery.
By The McGowan Institute For Regenerative Medicine | Grant of the Month | December 1, 2006
Co-PI(s) Michael Chancellor, MD; Douglas Chew, BS; Johnny Huard, PhD; Naoki Yoshimura, MD, PhD
Title Bioengineered Urethral Augmentation
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2006 | November 1, 2006
Co-PIs Michael Chancellor, MD; Douglas Chew, BS; Johnny Huard, PhD; Naoki Yoshimura, MD, PhD
Title Bioengineered Urethral Augmentation
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2006 | October 1, 2006
Co-PIs Kacey G. Marra, Ph.D., Albert D. Donnenberg, Ph.D., Vera S. Donnenberg, Ph.D., Stephen Badylak, D.V.M., M.D., Ph.D., and Howard D. Edington, M.D.
By The McGowan Institute For Regenerative Medicine | Grant of the Month | September 1, 2006
Co-PI(s) Marina V. Kameneva, PhD and Alan J. Russell, PhD
Title Next Steps in the Development of Drag Reducing Polymers for Treatment of Life-Threatening Hemmorrhagic Shock in Combat Casualties Using Small Volumes of Resuscitation Fluid
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2006 | August 1, 2006
Title Metastatic Colon Cancer, Stem Cells, and Artificial Bioreactors
Summary This study will focus on the cellular characterization of metastatic colon cancer in the liver and a 3-D perfusion culture instrument that recapitulates hepatic vasculature and microenvironment. Colon cancer is a very common cancer second only to lung cancer. Distant metastases are one of the worst prognostic signs as this places the patient in the most advanced staging category. Colon cancers generally spread through the lymphatics or through the portal venous system to the liver. The liver is the most frequent visceral site of metastatic dissemination and is the initial site of distant spread in one-third of recurring colon cancers, with two-thirds of patients having liver involvement at the time of death. The median survival after the detection of distant metastases range from 6 to 9 months (with heavy liver involvement) to 24 to 30 months (with initially small liver nodules).
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2006 | July 1, 2006
Title Cardiopulmonary Organ Engineering
Summary The aim of this proposal is to design solutions for vascular, cardiac, and pulmonary organ failure by building interactive teams of researchers focused on specific aspects of cardiopulmonary organ engineering. Our efforts will address a tissue engineered blood vessel, and a myocardial patch. The assembled research teams will function as cores of expertise that address common tasks associated with each of the projects. Five research cores will be established in the following areas:
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2006 | May 1, 2006
Title Pediatric Circulatory Support
Summary The PediaFlow™ is a miniature magnetically levitated turbodynamic VAD for pediatric patients ranging from birth weight to 15 kg. Our design is based on extensive computational modeling. CFD analysis was used to optimize the flow field for efficiency and hemocompatibility and reach a design point of 0.5 L/min at a 110 mm Hg pressure head.
The current (1st generation) PediaFlow™ design is 51 mm in length with a diameter of 28 mm. Its total mass is approximately 100 g. Prototypes are currently undergoing in vitro performance tests and flow path visualization and quantification. In vivo evaluation is planned during the current grant year.
By The McGowan Institute For Regenerative Medicine | Grant of the Month, Grant of the Month 2006 | April 1, 2006
- Susan Braunhut, Ph.D., professor of biological sciences at the University of Massachusetts at Lowell
- Lorraine Gudas, Ph.D., chairman of the pharmacology department and Revlon Pharmaceutical Professor of Pharmacology and Toxicology, Weill Medical College of Cornell University, New York City
- Ellen Heber-Katz, Ph.D., professor, molecular and cellular oncogenesis program, The Wistar Institute in Philadelphia
Shannon Odelberg, Ph.D., assistant professor, departments of internal medicine and neurobiology and anatomy, University of Utah, Salt Lake City - Hans-Georg Simon, Ph.D., a developmental biologist and assistant professor of pediatrics, Children’s Memorial Research Center and Northwestern University in Chicago
Title Mammalian Limb Restoration
Summary The regenerative ability of adult human tissues, organs, and appendages is typically very limited. The default mechanism of wound repair in humans and most other mammals is characterized by scar tissue formation. However, there is evidence for some site-specific regeneration-like processes during mammalian embryologic development and during the early postnatal period. In addition, there is lifelong self-renewal capability for selected cell populations such as hematopoietic cells, intestinal epithelium, and hepatocytes.