2017 ISAKOS Biennial Congress ePoster #301
Targeting Fibrosis-Customized Platelet-Rich Plasma for Optimized Skeletal Muscle Healing
Hongshuai Li, MD, PhD, Pittsburgh, PA UNITED STATES
Justin Hicks, BS, Winston-Salem, NC UNITED STATES
MaCalus V. Hogan, MD, MBA, Pittsburgh, PA UNITED STATES
Johnny Huard, PhD, Houston, TX UNITED STATES
University of Pittsburgh, Pittsburgh, PA, UNITED STATES
FDA Status Not Applicable
Neutralizing TGF-1 within PRP significantly promotes muscle regeneration while significantly reducing fibrosis.
Muscle injuries present very frequently in sports medicine and the current strategies to improve muscle healing are unsatisfactory mainly due to fibrosis. Platelet-Rich-Plasma (PRP) is an autologous whole blood derived bio-agent/biomaterial that is being investigated for use in muscle tissue healing. Although there is little clinical evidence to support its efficacy, autologous PRP has been proposed empirically for the treatment of sports-related muscle injuries due to the abundant autologous growth factors released by PRP. However, besides the beneficial growth factors, PRP also contains high concentrations of “negative/deleterious” cytokines and growth factors such as high concentrations of transforming growth factor-beta 1 (TGF-ß1) shown to be a deleterious agent for optimal skeletal muscle repair. The purpose of this study is to test if neutralizing TGF- ß 1's action within PRP, through neutralization antibodies, could improve PRP's beneficial effect on skeletal muscle repair.
PRP was isolated from in-bred Fisher rats. TGF-1 neutralization antibody (Ab) was used to block the TGF-b1 within the PRP prior to injection. The effects of customized PRP (TGF-1 neutralized PRP) on muscle healing was tested on a cardiotoxin (CTX) induced muscle injury model.
A significant increase in the numbers of regenerative myofibers was observed in the PRP and customized PRP groups compared to the untreated control. A significant decrease in collagen deposition was observed in customized PRP groups when compared to the control and PRP groups. Significantly enhanced angiogenesis and more Pax-7 positive satellite cells were found in the PRP and customized PRP groups compared to the control group. Macrophage infiltration was increased in the customized PRP groups when compared with the PRP group. More M2 macrophages were recruited to the injury site in the customized PRP groups when compared with the PRP and control groups.
Neutralizing TGF-1 within PRP significantly promotes muscle regeneration while significantly reducing fibrosis. Not only did the neutralization reduce fibrosis, it enhanced angiogenesis, prolonged satellite cell activation, and recruited a greater number of M2 macrophages to the injury site which also contributed to the efficacy that the customized PRP had on muscle healing.
To improve the beneficial effect of PRP through its modification by eliminating bioactive factors known to be deleterious for skeletal muscle will not only provide a novel strategy to obtain optimized muscle healing, but also open the door for a new paradigm of PRP research for other musculoskeletal tissue healing.