Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

Principal Investigator: LEE, W.P. ANDREW
Institution Receiving Award: JOHNS HOPKINS UNIVERSITY
Program: PRORP
Proposal Number: OR090652
Award Number: W81XWH-10-1-0927
Funding Mechanism: Hypothesis Development Award
Partnering Awards:
Award Amount: $119,573.49


Reconstructive transplantation has become a novel therapeutic modality for the treatment of devastating injuries such as craniofacial defects or loss of a hand. In the past decade, over 100 different composite tissue allotransplantation (CTA) procedures have been performed around the world, including 52 hand and 8 facial transplants, with encouraging graft survival and excellent functional outcomes.

Although a clinical reality, broader clinical application of CTA has been hampered by particularly strong rejection of the skin component, necessitating long-term high-dose multi-drug maintenance immunosuppression. This medication toxicity could result in metabolic and infectious complications or malignancy.

We hypothesize that mesenchymal stem cell (MSC) therapy will improve nerve regeneration and enhance immunomodulation after CTA. MSC are adult stem cells that are present in multiple tissues, including bone marrow, adipose tissue, skin, heart, and placenta, and can be isolated and expanded in the laboratory. Previous research has shown that MSC have potent immunosuppressive properties to inhibit the activation and proliferation of immune cells. In addition, there is growing evidence of enhanced nerve regeneration as a result of MSC therapy. These combined effects make MSC an ideal candidate therapy for CTA procedures.

The effect of MSC will be tested in a rat sciatic nerve transection model (nerve regeneration) as well as a rat hind limb transplant model (nerve regeneration and immunomodulation). Analysis will be performed by video gait kinematics, electrophysiology, histomorphometry, and immunohistochemistry.