Collagen-VI Supplementation by Cell Transplantation Improves Muscle Regeneration in Ullrich Congenital Muscular Dystrophy Model Mice

Type 6 collagen (COL6) is produced by mesenchymal stromal cells (MSC) in skeletal muscle, and its gene mutation is the cause of Ullrich congenital muscular dystrophy (UCMD). To test whether COL6 supplementation has a therapeutic effect for UCMD, we conducted in vivo and in vitro experiments using healthy induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) and COL6-deficient iMSCs (KO-iMSCs). The transplantation of these iMSCs or primary MSCs into the skeletal muscle of immunodeficient UCMD model mice demonstrated that muscle regeneration and maturation were promoted only in the region supplemented with COL6. In addition, co-culture experiments of skeletal muscle satellite cells derived from UCMD model mice (Col6a1KO-MuSCs) showed iMSCs but not KO-iMSCs could improve the proliferation, differentiation, and maturation of Col6a1KO-MuSCs. These findings indicate that COL6 supplementation improves muscle regeneration and maturation in UCMD model mice and will help elucidate the pathology of UCMD and establishment of effective treatments.