Grants We Funded
In 2019, The Plastic Surgery Foundation (The PSF) awarded 33 investigator-initiated projects and allocated $891,274 to support the newest, clinically relevant research in plastic surgery.
The American Society of Plastic Surgeons/PSF leadership is committed to continuing to provide high levels of investigator-initiated research support to ensure that plastic surgeons have the needed research resources to be pioneers and innovators in advancing the practice of medicine.
Search The PSF database to have easy access to full-text grant abstracts from past PSF-funded research projects 2003 to present. All abstracts are the work of the Principal Investigators and were retrieved from their PSF grant applications. Several different filters may be applied to locate abstracts specific to a particular focus area, or PSF funding mechanism.
FReP cell-based Therapy for Skeletal Muscle Generation
Zhong Zheng PhD
The Regents of the University of California, Los Angeles
National Endowment for Plastic Surgery Grant
Tissue Engineering, Wounds / Scar
Today, an urgent need exists for a therapeutic in vivo cell-based strategy that can promote de novo formation of skeletal muscle tissues to manage large-volume damage caused by traumatic injuries, salvage surgeries, and congenital and acquired musculoskeletal deformities. A principle challenge of in vivo skeletal muscle establishment is to introduce enough safe myogenic progenitor cells to the target site. The current embryonic stem cell (ESC)-based therapies are hindered by the moral dilemma and risk of rejection and tumor formation. Autologous myoblast and mesenchymal stem cell (MSC)-based skeletal muscle regeneration also faces numerous problems, such as the highly invasive cell-harvesting procedures, inadequate cell availability, and variable regenerative efficacy. Although using patient-specific induced pluripotent stem cells (iPSCs) can bypass many ethical and immunological concerns, tumorigenesis remains a significant obstacle to their safe clinical application. Recently, we pioneered a novel, technically feasible fibromodulin (FMOD)-based reprogramming approach that avoids genetic modification to directly convert somatic cells into multipotent cells. These FMOD reprogrammed (FReP) cells can engraft and establish new skeletal muscle tissues in severe combined immunodeficiency (SCID) mouse models without tumor formation. To establish a large volume of muscle mass, an appropriate matrix is essential for cellular localization and retention to provide a microenvironment favorable for proliferation and myogenesis. Since our long-term goal is to establish a practical and safe FReP cell-based de novo skeletal muscle formation procedure, a biocompatible, bioresorbable, and myogenesis-favoring matrix will be developed initially to encapsulate FReP cells in this study (Aim 1). Subsequently, we will advance the efficacy of encapsulated FReP cells for in vivo skeletal muscle generation under both non-injured and injured circumstances using muscle pouch and critical-sized muscle injured SCID mouse models, respectively (Aim 2 and 3). Results from this study will significantly advance the generation of new skeletal muscle for both reconstructive and esthetic purposes. Eventually, this research endeavor will provide an essential foundation for translating our project into Investigational New Drug (IND)-enabling studies for the FDA. The present studies will also provide sufficient proof-of-principle to enable the FReP cell-based platform technologies to be applied to a broad-range of severe tissue injuries such as bone damages. The simple FMOD induction of multipotent cells without genome integration has potential to shift the paradigm of reprogramming autologous cells for tissue reconstruction to a safe, protein-based process that avoids tumorigenesis.
Dr. Zhong Zheng received his BS in Biological Sciences and Biotechnology in 2001, and subsequently his MS and PhD in 2005, all from Tsinghua University in Beijing, China. Additionally, he received postdoctoral training in 2008-2012 from the Department of Orthopaedic Surgery of the UCLA David Geffen School of Medicine, as well as the Dental and Craniofacial Research Institute and Section of Orthodontics of the UCLA School of Dentistry. He currently is an Adjunct Assistant Professor at the UCLA School of Dentistry. He has been committed to using fibromodulin (FMOD) to manage skin wound healing processes, and has published related studies in the American Journal of Pathology and the Journal of Investigative Dermatology. Moreover, Dr. Zheng is the first person to generate the FMOD-related peptide to reduce scar formation. Currently, Dr. Zheng is focused on developing cell-based regenerative medicines for musculoskeletal tissue engineering, such as using human perivascular cells for bone regeneration. He also successfully reverted human fibroblasts into low tumorigenic multipotent cells with osteogenesis and myogenesis potential.