LONG-TERM SURVIVAL OF ALLOGRAFTED MUSCLE PRECURSOR CELLS FOLLOWING A LIMITED PERIOD OF TREATMENT WITH CYCLOSPORIN-A

Abstract

In the mouse, skeletal muscle can be transplanted successfully in the form of a suspension of its mononucleate precursors. Eventual therapeutic application of this technique by the implantation of precursor cells derived from normal muscle into myopathic individuals would require a means of preventing allograft rejection applicable to man. The use of the drug cyclosporin A (CyA) was investigated as a means of prolonging the survival in mice of allografts of mononucleate muscle cells made into a region of regenerating host muscle. CyA was administered to the hosts at doses of either 75 or 150 mg/kg body wt per day for 42 days from the day of grafting. By using isoenzyme allotypes as markers of host and donor tissues, allografted mononucleate cells become incorporated in host muscle fibers. The mosaic host/donor muscle fibers so formed survive for as long as the experiment continued, a maximum of 107 days after grafting, or 65 days after the end of CyA treatment.