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

Autor: Shoshan Knaän-Shanzer, Hester Boersma, Anabel S de la Garza-Rodea, Antoine A.F. de Vries, Dirk W. van Bekkum, Manuel A F V Gonçalves, Ietje van der Velde
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Adult
Stromal cell
Time Factors
Muscle Fibers
Skeletal
Biomedical Engineering
lcsh:Medicine
Bone Marrow Cells
Biology
Mesenchymal Stem Cell Transplantation
Andrology
Cell therapy
Diffusion
Mice
Cardiotoxin
medicine
Animals
Humans
Regeneration
Muscle
Skeletal
Cells
Cultured
Cell Proliferation
Transplantation
Regeneration (biology)
Mesenchymal stem cell
lcsh:R
Skeletal muscle
Mesenchymal Stem Cells
Cell Biology
beta-Galactosidase
Immunohistochemistry
medicine.anatomical_structure
Female
Fibroblast Growth Factor 2
Bone marrow
Stromal Cells
Bone marrow Cell therapy Duchenne muscular dystrophy Human mesenchymal stromal cell NOD/SCID mouse Skeletal muscle regeneration side population cells human adipose-tissue stem-cells muscular-dystrophy satellite cells in-vivo autologous transplantation precursor cells mdx mice myoblast transplantation
Zdroj: Cell Transplantation, Vol 20 (2011)
Cell Transplantation, 20(2), 217-231
ISSN: 1555-3892
0963-6897
Popis: 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.
Databáze: OpenAIRE
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