Flk-1<sup>+</sup>Adipose-Derived Mesenchymal Stem Cells Differentiate into Skeletal Muscle Satellite Cells and Ameliorate Muscular Dystrophy in MDX Mice

Liu, Yanning; Xiao, Yan; Sun, Zhao; Chen, Bin; Han, Qin; Li, Jing; Zhao, Robert Chunhua

doi:10.1089/scd.2006.0118

Cited by 115 publications

(85 citation statements)

References 47 publications

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“…tibialis anterior muscles (TAMs) of dystrophic (i.e., mdx) mice at 6 months after local injection of massively Cells were then separated from the remaining tissue fragments by filtration through a 30-µm pore size nylon expanded (>200 population doublings) MSCs isolated from AT of young donors. Integration into regenerating mesh filter (Miltenyi Biotec, Bergisch Gladbach, Germany), collected by centrifugation, and seeded in growth myofibers, either directly or via satellite cell intermediates, also has been documented for MSCs isolated from medium (GM) composed of DMEM, 100 U/ml penicillin, 100 µg/ml streptomycin, and 10% fetal bovine AT (54), BM (23,75), and SM (22) of adult donors as well as from fetal BM (7). These studies were performed serum (FBS; Invitrogen) in plastic 25-cm 2 cell culture flasks (CELLSTAR; Greiner Bio-One, Frickenhousen, either in mdx mice or in artificially injured muscles of immunodeficient mice and generally yielded less hybrid Germany) and incubated at 37°C in humidified air with 10% CO 2 .…”

Section: Introductionmentioning

confidence: 99%

Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

et al. 2012

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Mesenchymal stem cells (MSCs) of mammals have been isolated from many tissues and are characterized by their aptitude to differentiate into bone, cartilage, and fat. Differentiation into cells of other lineages like skeletal muscle, tendon/ligament, nervous tissue, and epithelium has been attained with MSCs derived from some tissues. Whether such abilities are shared by MSCs of all tissues is unknown. We therefore compared for three human donors the myogenic properties of MSCs from adipose tissue (AT), bone marrow (BM), and synovial membrane (SM). Our data show that human MSCs derived from the three tissues differ in phenotype, proliferation capacity, and differentiation potential. The division rate of AT-derived MSCs (ATMSCs) was distinctly higher than that of MSCs from the other two tissue sources. In addition, clear donorspecific differences in the long-term maintenance of MSC proliferation ability were observed. Although similar in their in vitro fusogenic capacity with murine myoblasts, MSCs of the three sources contributed to a different extent to skeletal muscle regeneration in vivo. Transplanting human AT-, BM-, or SM-MSCs previously transduced with a lentiviral vector encoding β-galactosidase into cardiotoxin-damaged tibialis anterior muscles (TAMs) of immunodeficient mice revealed that at 30 days after treatment the frequency of hybrid myofibers was highest in the TAMs treated with AT-MSCs. Our finding of human-specific β-spectrin and dystrophin in hybrid myofibers containing human nuclei argues for myogenic programming of MSCs in regenerating murine skeletal muscle. For the further development of MSC-based treatments of myopathies, AT-MSCs appear to be the best choice in view of their efficient contribution to myoregeneration, their high ex vivo expansion potential, and because their harvesting is less demanding than that of BM-or SM-MSCs.

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Section: Introductionmentioning

confidence: 99%

Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

et al. 2012

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“…In myogenesis, muscle cells and adipocytes transdifferentiate into MSCs. In this process the myogenin and MyoD myogenic markers are expressed (6)(7)(8)(9). However, during the transdifferentiation into adipocytes, adipogenic transcription factors including CCAAT/enhance binding protein (C/EBP) α and peroxisome proliferator-activated receptor (PPAR) γ participate in the process at the preadipocyte stage (2,4,10).…”

Section: Introductionmentioning

confidence: 99%

Functional study of Villin 2 protein expressed in longissimus dorsi muscle of Korean native cattle in different growth stages

Jin

Han²,

Xu³

et al. 2012

BMB Reports

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The aim of this study was to investigate protein profiles related to the induction of adipogenesis within the bovine longissimus dorsi muscle (BLDM) by proteomic analysis. We analyzed BLDM proteins at different growth stages to clarify the physiological mechanisms of marbled muscle development in 20 head of Korean native cattle (11 month: 10 head, 17 month: 10 head). BLDM proteins were analyzed by two-dimensional electrophoresis and image analysis. Villin 2 was specifically identified by mass spectrometry and a protein search engine. Villin 2 protein expression in BLDM decreased during the fat development stage in test steers. In a Western blot cell culture study of spontaneously immortal bovine muscle fibroblasts, the abundance of Villin 2 was shown to be down-regulated during differentiation into muscle. In 3T3-L1 mouse embryonic fibroblasts, Villin 2 was decreased during differentiation into adipocytes. The results suggest that Villin 2 may be related to the induction of transdifferentiation and adipogenesis in bovine longissimus dorsi muscle. [BMB reports 2012; 45(2): 102-107]

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“…Evidence provided so far for the ability of MSCs to differentiate along the myogenic lineage is conflicting. Although some previous studies assigned myogenic properties to MSCs by demonstrating their in vitro and in vivo differentiation into satellite cells and myoblasts and their ability to form myotube-like structures through homotypic fusion [19,21] , others regard the myogenic reprogramming of the MSCs to be the consequence of their fusion with inherently myogenic cells [2,22,23] . Whether this contradiction can be attributed to the differences in MSC origin, the model used or the read-out methods applied, remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration

Garza-Rodea¹

2015

WJEM

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AIM:To study regeneration of damaged human and murine muscle implants and the contribution of added xenogeneic mesenchymal stem cells (MSCs). METHODS:Minced human or mouse skeletal muscle tissues were implanted together with human or mouse MSCs subcutaneously on the back of non-obese diabetic/ severe combined immunodeficient mice. The muscle tissues (both human and murine) were minced with scalpels into small pieces (< 1 mm 3 ) and aliquoted in portions of 200 mm 3 . These portions were either cryopreserved in 10% dimethylsulfoxide or freshly implanted. Syngeneic or xenogeneic MSCs were added to the minced muscles directly before implantation. Implants were collected at 7, 14, 30 or 45 d after transplantation and processed for (immuno)histological analysis. The progression of muscle regeneration was assessed using a standard histological staining (hematoxylin-phloxinsaffron). Antibodies recognizing Pax7 and von Willebrand factor were used to detect the presence of satellite cells and blood vessels, respectively. To enable detection of the bone marrow-derived MSCs or their derivatives we used MSCs previously transduced with lentiviral vectors expressing a cytoplasmic LacZ gene. X-gal staining of the fixed tissues was used to detect β-galactosidase-positive cells and myofibers. RESULTS:Myoregeneration in implants of fresh murine muscle was evident as early as day 7, and progressed with time to occupy 50% to 70% of the implants. Regeneration of fresh human muscle was slower. These observations of fresh muscle implants were in contrast to the regeneration of cryopreserved murine muscle that proceeded similarly to that of fresh tissue except for day 45 (P < 0.05). Cryopreserved human muscle showed minimal regeneration, suggesting that the freezing ORIGINAL ARTICLE Clinical Trials Studyprocedure was detrimental to human satellite cells. In fresh and cryopreserved mouse muscle supplemented with LacZ-tagged mouse MSCs, β-galactosidase-positive myofibers were identified early after grafting at the wellvascularized periphery of the implants. The contribution of human MSCs to murine myofiber formation was, however, restricted to the cryopreserved mouse muscle implants. This suggests that fresh murine muscle tissue provides a suboptimal environment for maintenance of human MSCs. A detailed analysis of the histological sections of the various muscle implants revealed the presence of cellular structures with a deviating morphology. Additional stainings with alizarin red and alcian blue showed myofiber calcification in 50 of 66 human muscle implants, and encapsulated cartilage in 10 of 81 of murine muscle implants, respectively. CONCLUSION:In mouse models the engagement of human MSCs in myoregeneration might be underestimated. Furthermore, our model permits the dissection of speciesspecific factors in the microenvironment. Core tip: The translational relevance of animal models for tissue repair is often ambiguous. We describe here a murine model for the comparison of the regeneration of damaged human and murine skele...

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Flk-1⁺Adipose-Derived Mesenchymal Stem Cells Differentiate into Skeletal Muscle Satellite Cells and Ameliorate Muscular Dystrophy in MDX Mice

Cited by 115 publications

References 47 publications

Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

Functional study of Villin 2 protein expressed in longissimus dorsi muscle of Korean native cattle in different growth stages

Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration

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Flk-1+Adipose-Derived Mesenchymal Stem Cells Differentiate into Skeletal Muscle Satellite Cells and Ameliorate Muscular Dystrophy in MDX Mice

Cited by 115 publications

References 47 publications

Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

Functional study of Villin 2 protein expressed in longissimus dorsi muscle of Korean native cattle in different growth stages

Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration

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Flk-1⁺Adipose-Derived Mesenchymal Stem Cells Differentiate into Skeletal Muscle Satellite Cells and Ameliorate Muscular Dystrophy in MDX Mice