Syngeneic Myoblast Transplantation Improves Muscle Function in a Murine Model of X-Linked Myotubular Myopathy. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Lim, Hyun Ju; Joo, Sunyoung; Oh, Seh-Hoon; Jackson, John D.; Eckman, Delrae M.; Bledsoe, Tiffaney M.; Pierson, Christopher R.; Childers, Martin K.; Atala, Anthony; Yoo, James J.
• Is Part Of: Cell transplantation. Volume 24:Issue 9(2015)
• Page Start: 1887
• Page End: 1900
• Publication Date: 2015-09
• Subjects: X-linked myotubular myopathy (XLMTM) -- Myoblast -- Syngeneic cell transplantation -- Muscle regeneration -- Muscle physiologic functions; Cell transplantation -- Periodicals; Cell Transplantation; Cell transplantation; Electronic journals; Periodicals; Periodicals; 571.638
• DOI: 10.3727/096368914X683494
• Languages: English
• ISSNs: 0963-6897

Abstract

X-linked myotubular myopathy (XLMTM) is an isogenic muscle disease characterized by progressive wasting of skeletal muscle, weakness, and premature death of affected male offspring. Recently, the XLMTM gene knock-in mouse, Mtm1 p.R69C, was found to have a similar phenotype as the MTM1 gene mutation in humans (e.g., central nucleation of small myofibers, attenuated muscle strength, and motor unit potentials). Using this rodent model, we investigated whether syngeneic cell therapy could mitigate muscle weakness. Donor skeletal muscle-derived myoblasts were isolated from C57BL6 wild-type (WT) and Mtm1 p.R69C (KI) mice for transplantation into the gastrocnemius muscle of recipient KI mice. Initial experiments demonstrated that donor skeletal muscle-derived myoblasts from WT and KI mice remained in the gastrocnemius muscle of the recipient KI mouse for up to 4 weeks posttransplantation. KI mice receiving syngeneic skeletal muscle-derived myoblasts displayed an increase in skeletal muscle mass, augmented force generation, and increased nerve-evoked skeletal muscle action potential amplitude. Taken together, these results support our hypothesis that syngeneic cell therapy may potentially be used to ameliorate muscle weakness and delay the progression of XLMTM, as application expands to other muscles.