Dynamic distribution of bone marrow-derived mesenchymal stromal cells and change of pathology after infusing into mdx mice

Abstract

Mesenchymal stromal cells (MSC) are attractive candidates for the treatment of Duchenne muscular dystrophy (DMD) but how the donor MSC distribute in multiple organs and whether the increased dystrophin leads to a change in the pathology of mdx mice is still uncertain. In this research we detected the distribution of MSC and the pathology of mdx mice after MSC infusion. MSC were isolated from rat bone marrow (BM) and expanded in proliferation medium. MSC of the fifth passage were delivered intravenously into irradiated mdx mice. The distribution of MSC labeled by [3H]TdR into a recipient's organs was calculated by radioactivity. The expression of dystrophin was detected at weeks 4, 8, 12 and 16 after MSC transplantation by immunofluorescence staining, RT-PCR and Western blot. Serum creatine kinase (CK) and centrally nucleated fiber (CNF) were also detected to assess the change in pathology. 24-48 h after transplantation, MSC were mainly found in the BM, liver and lung. The radioactivity in these organs decreased, whereas skeletal and myocardial muscle radioactivity increased gradually over time. In accordance with the increased radioactivity in skeletal muscle, the amount of dystrophin-positive myofibers increased. Furthermore, serum CK and CNF decreased slightly, suggesting specific pathophysiologic features of the dystrophic muscle were partially restored. Upon certification of the distribution of transplanted MSC in irradiated mdx mice, we found evidence of myogenic differentiation of MSC in skeletal muscle. This research may help us understand the mechanism of therapy of MSC transplantation.