Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice

Cell Transplantation

Article

Antoine A. F. De Vries¹  Ietje Van Der Velde¹  Hester Boersma¹  Shoshan Knaän-Shanzer¹  Dirk W. Van Bekkum¹  Manuel A. F. V. Gonçalves¹  Anabel S. De La Garza-Rodea¹ 

[1] Virus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands;

关键词: Bone marrow;    Cell therapy;    Duchenne muscular dystrophy;    Human mesenchymal stromal cell;    NOD/SCID mouse;    Skeletal muscle regeneration;   

DOI  :  10.3727/096368910X522117

 received in 2009-12-07, accepted in 2010-06-30,  发布年份 2011

来源: Sage Journals

【 摘 要 】

Mesenchymal stromal cells (MSCs) are attractive for cellular therapy of muscular dystrophies as they are easy to procure, can be greatly expanded ex vivo, and contribute to skeletal muscle repair in vivo. However, detailed information about the contribution of bone marrow (BM)-derived human MSCs (BM-hMSCs) to skeletal muscle regeneration in vivo is very limited. Here, we present the results of a comprehensive study of the fate of LacZ-tagged BM-hMSCs following implantation in cardiotoxin (CTX)-injured tibialis anterior muscles (TAMs) of immunodeficient mice. β-Galactosidase-positive (β-gal+) human-mouse hybrid myofibers (HMs) were counted in serial cross sections over the full length of the treated TAMs of groups of mice at monthly intervals. The number of human cells was estimated using chemiluminescence assays. While the number of human cells declined gradually to about 10% of the injected cells at 60 days after transplantation, the number of HMs increased from day 10 onwards, reaching 104 ± 39.1 per TAM at 4 months postinjection. β-gal+ cells and HMs were distributed over the entire muscle, indicating migration of the former from the central injection site to the ends of the TAMs. The identification of HMs that stained positive for human spectrin suggests myogenic reprogramming of hMSC nuclei. In summary, our findings reveal that BM-hMSCs continue to participate in the regeneration/remodeling of CTX-injured TAMs, resulting in ±5% HMs at 4 months after damage induction. Moreover, donor-derived cells were shown to express genetic information, both endogenous and transgenic, in recipient myofibers.

【 授权许可】

Unknown   
© 2011 Cognizant Comm. Corp.

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