Badylak Lab Team Members Receive NIH Grants for Regenerative Medicine Projects
Team members in the laboratory of McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, professor in the Department of Surgery, University of Pittsburgh, and director of the Center for Pre-Clinical Tissue Engineering within the McGowan Institute, are the recipients of two National Institute of Health (NIH) F31 Grants. The two PhD candidates receiving the Ruth L. Kirschstein National Research Service Award (NRSA) are Brian Sicari (pictured top) and Denver Faulk (pictured bottom).
The NRSA predoctoral fellowship award is named after Ruth L. Kirchstein, MD, the first woman director of an NIH Institute. Aside from Dr. Kirschstein’s scientific accomplishments in polio vaccine development, she was a champion of research training and a strong advocate for the inclusion of underrepresented individuals in the scientific workforce.
The titles and abstracts of Mr. Sicari’s and Mr. Faulk’s grants follow:
Project Title: Constructive Remodeling by ECM Scaffolds within Aging Skeletal Muscle
Abstract: Following injury, the inherent regenerative response of skeletal muscle depends on an activated microenvironment consisting of muscle progenitor cells and a heterogeneous macrophage phenotype. These microenvironmental factors can be negatively impacted through musculoskeletal disease, volumetric muscle loss (VML), and the decreased regenerative capacity of stem cells and immunosenesence associated with advanced age. Biologic scaffolds composed of extracellular matrix (ECM) have been used to promote the constructive remodeling of defects in a variety of soft tissues. These surgically placed scaffolds are composed of growth factors and matricryptic peptides which are able to positively impact the skeletal muscle microenvironment by recruiting progenitor cells and promoting an M1 to M2 macrophage phenotypic transition. Furthermore, ECM scaffolds have been used to effectively augment the skeletal muscle response to VML. The current proposal seeks to examine the ability of ECM scaffolds to mitigate age-related changes to the skeletal muscle microenvironment through increased myogenic progenitor cell recruitment and modulation of macrophage phenotype.
Title: Engineering a Functional Liver Graft for Treatment of End Stage Liver Disease
Abstract: Approximately 27,000 deaths occur annually in the United States alone from patients with end-stage liver disease. With an aging population, this number is only expected to increase. The current definitive treatment is orthotropic transplantation. However, due to high demand there exists a critical shortage of donor livers. Those patients fortunate enough to receive a transplant are burdened with the risk of chronic rejection and the morbidity associated with a lifelong regimen of immunosuppressant therapy. This treatment is especially difficult for elderly patients.
This proposal addresses a regenerative medicine strategy for engineering an implantable liver graft for patients with end-stage liver failure. It is based upon three fundamental concepts: 1) the native ECM of the liver, including the three-dimensional untrastructure and composition, represents an ideal and required substrate for liver regeneration, 2) whole liver ECM scaffolds retain the three-dimensional macrostructure, the native microvascular network, and the bile drainage system, allowing for complete recellularization of all native cell types, and 3) liver regeneration can be promoted when reseeded whole liver ECM grafts are placed in the appropriate three-dimensional microenvironment; specifically, in-situ in patients with liver failure.
The objectives of the proposed research are to (1) establish an effective method for reseeding a three-dimensional liver scaffold, with a focus on systematically seeding both parenchymal and non-parenchymal cells in their native location and to (2) evaluate the host response to the implantation of a reseeded three-dimensional liver scaffold. Additionally, the methods and techniques developed in this study present an important step towards the establishment of decellularization and recellularization criteria necessary to successfully produce the first fully functional bioengineered livers for organ transplantation and drug discovery.
Congratulations to Brian and Denver!