Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane

Abstract

We have demonstrated previously that adult human synovial membrane-derived mesenchymal stem cells (hSM-MSCs) have myogenic potential in vitro (De Bari, C., F. Dell'Accio, P. Tylzanowski, and F.P. Luyten. 2001. Arthritis Rheum. 44:1928–1942). In the present study, we have characterized their myogenic differentiation in a nude mouse model of skeletal muscle regeneration and provide proof of principle of their potential use for muscle repair in the mdx mouse model of Duchenne muscular dystrophy. When implanted into regenerating nude mouse muscle, hSM-MSCs contributed to myofibers and to long term persisting functional satellite cells. No nuclear fusion hybrids were observed between donor human cells and host mouse muscle cells. Myogenic differentiation proceeded through a molecular cascade resembling embryonic muscle development. Differentiation was sensitive to environmental cues, since hSM-MSCs injected into the bloodstream engrafted in several tissues, but acquired the muscle phenotype only within skeletal muscle. When administered into dystrophic muscles of immunosuppressed mdx mice, hSM-MSCs restored sarcolemmal expression of dystrophin, reduced central nucleation, and rescued the expression of mouse mechano growth factor.

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

“…Similar contribution to the satellite cell pool has been demonstrated in injured mouse muscles for muscle SP cells, 21 muscle-derived floating populations, 42 CD133 ϩ cells, 24 and synovial membrane-derived mesenchymal stem cells. 75 However, this is the first time that this behavioral feature is described in highly damaged muscles such as those in GRMD dogs. In addition to their participation on fiber regeneration and satellite cell formation, we observed that MuStem cells intriguingly gave rise to interstitial cells.…”

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

“…Interestingly, synovium-derived MSCs had great differentiation potential for adipogenesis and osteogenesis as well as chondrogenesis. De Bari and colleagues previously reported that synovium-derived MSCs had myogenic potential both in vitro and in vivo (27), suggesting the high multipotentiality of synovium-derived MSCs.…”

Updates on stem cells and their applications in regenerative medicine

“…This further supported the multipotent potential of CFU-Fs. Similar cells have been isolated from different mesenchymal tissues, including synovia (De Bari et al, 2003), tendons (Salingcarnboriboon et al, 2003), skeletal muscles (Bosch et al, 2000) and adipose tissue (Zuk et al, 2001Erickson et al, 2002), including the fat pad of the knee joint (Dragoo et al, 2003). These MSCs were also found in peripheral blood (Kuznetsov et al, 2001); however, their frequency is probably extremely low or variable (Zvaifler et al, 2000) and they are characterized by different cell surface markers (Table 1).…”