Hematopoietic cell transplantation directly into dystrophic muscle fails to reconstitute satellite cells and myofibers

Abstract

We sought to determine whether wild-type hematopoietic cell transplantation directly into muscle could restore dystrophin expression in a relevant preclinical canine model of Duchenne muscular dystrophy. In recipients rendered tolerant to their dog leukocyte antigen-matched unaffected littermates through hematopoietic stem cell transplantation, intramuscular injection of donor marrow cells produced no evidence of dystrophin expression, and clonal analysis of satellite cells failed to reveal any donor contribution.

Figure 1

Chimerism analyses from peripheral blood, muscle biopsies, and cultured muscle satellite cells from a DMD-affected dog given intra-muscular marrow injections from the unaffected HCT donor. Assays performed by PCR amplification of variable number tandem repeats [15] that differentiated donor and recipient. Muscle biopsies demonstrate contribution from both donor and recipient representative of the hematopoietic cells present in muscle tissue, while cultured satellite cells failed to show donor contribution. (PB; peripheral blood)

Figure 2

Reverse-transcription-PCR reactions for dystrophin and β-actin in muscle biopsies from a DMD-affected dog demonstrate no dystrophin mRNA expression above the background after intramuscular marrow injections from the unaffected HCT donor.