Customizing PRP “Ingenious”

A June 5, 2013 scientific article by Satoshi Terada, M.D., et al. recently appeared in the Journal of Bone and Joint Surgery (JBJS). The study, “Use of an Antifibrotic Agent Improves the Effect of Platelet-Rich Plasma [PRP] on Muscle Healing After Injury, ” was sufficiently interesting to provoke an invited commentary. Christopher H. Evans, Ph.D., D.Sc. of Beth Israel Deaconess Medical Center, Boston, Massachusetts, was a referee on the paper and was asked by those at JBJS to give his thoughts.

Dr. Evans, concerned about PRP being the latest ortho-panacea, says it is “administered promiscuously for whatever ails the musculoskeletal system.” Interestingly, he notes that ingredients that are an advantage in one setting may be a disadvantage in another. For example, vascular endothelial growth factor (VEGF), a prominent angiogenic component of PRP, might be helpful for bone healing, which has an absolute need for angiogenesis, but a hindrance for repairing cartilage, which is avascular.

Dr. Evans indicates that Dr. Terada and colleagues do address the point that PRP cannot be all things to all tissues. Their solution is to customize PRP for specific indications; they used a murine model of skeletal muscle injury and repair. PRP has the potential to improve healing by enhancing angiogenesis and myoblast proliferation, but the presence of TGF-b impairs healing by promoting fibrosis and inhibiting satellite cell differentiation.

To improve the performance of PRP in their model, the investigators simultaneously treated the injured mice with losartan, an orally active inhibitor of the Smad signaling pathway used by TGF-b. This accelerated the rate of muscle vascularization while inhibiting fibrosis, leading to improved functional recovery. Losartan is already approved by the FDA for the treatment of hypertension and congestive heart failure. This, says Dr. Evans, should facilitate the clinical translation of their findings, assuming that short-term use of losartan does not have adverse cardiovascular sequelae in subjects who do not otherwise need it. The authors, as well as Dr. Evans, point out that further work is needed to establish the optimal dose, timing, and frequency of application.

Dr. Evans told OTW, “I thought that the approach of customizing the PRP to the biological need is quite ingenious. Most practitioners just slap it on willy-nilly, regardless of the indication.”

Asked where he thinks we will be with PRP in five years, Dr. Evans told OTW, “I am concerned that in five years, PRP might turn out to be another non-event: a fashionable, new, relatively untested panacea that did not stand up to scrutiny. However, if we could learn more about this product, standardize it, ask the right questions and do the necessary research, perhaps it could form the basis of something useful. The paper I reviewed by Terada et al. suggests one way forward in this context.”