Clonal Multipotency of Skeletal Muscle-Derived Stem Cells Between Mesodermal and Ectodermal Lineage

Tamaki, Toru; Okada, Yoshinori; Uchiyama, Yoshiyasu; Tono, Kayoko; Masuda, Maki; Wada, Mika; Hoshi, Akio; Ishikawa, Tetsuya; Akatsuka, Akira

doi:10.1634/stemcells.2006-0746

Cited by 69 publications

(96 citation statements)

References 32 publications

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“…Stem/progenitor cells isolated from murine and human skeletal muscles by various methods give rise to progeny cells with neuronal and glial phenotypes (12,(32)(33)(34)(35)(36). Populations of slowly adhering cells isolated from skeletal muscle via the modified preplate technique called muscle-derived stem/progenitor cells (MDSPCs) (37)(38)(39) are characterized by sustained self-renewal, long-term proliferation, and multipotent differentiation capacities (37,40,41).…”

Section: Introductionmentioning

confidence: 99%

Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration

Lavasani¹,

Thompson²,

Pollett³

et al. 2014

J. Clin. Invest.

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Peripheral nerve injuries and neuropathies lead to profound functional deficits. Here, we have demonstrated that muscle-derived stem/progenitor cells (MDSPCs) isolated from adult human skeletal muscle (hMDSPCs) can adopt neuronal and glial phenotypes in vitro and ameliorate a critical-sized sciatic nerve injury and its associated defects in a murine model. Transplanted hMDSPCs surrounded the axonal growth cone, while hMDSPCs infiltrating the regenerating nerve differentiated into myelinating Schwann cells. Engraftment of hMDSPCs into the area of the damaged nerve promoted axonal regeneration, which led to functional recovery as measured by sustained gait improvement. Furthermore, no adverse effects were observed in these animals up to 18 months after transplantation. Following hMDSPC therapy, gastrocnemius muscles from mice exhibited substantially less muscle atrophy, an increase in muscle mass after denervation, and reorganization of motor endplates at the postsynaptic sites compared with those from PBS-treated mice. Evaluation of nerve defects in animals transplanted with vehicle-only or myoblast-like cells did not reveal histological or functional recovery. These data demonstrate the efficacy of hMDSPC-based therapy for peripheral nerve injury and suggest that hMDSPC transplantation has potential to be translated for use in human neuropathies.

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Section: Introductionmentioning

confidence: 99%

Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration

Lavasani¹,

Thompson²,

Pollett³

et al. 2014

J. Clin. Invest.

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“…Recently, the validity of the in vitro neurosphere-formation assay as a measure of clonality and multipotentiality [3][4][5], and as an accurate predictor of the in vivo number of stem cells in a tissue [6], has been called into question. Many laboratories have used sphere-forming assays to identify stem cells in various tissue types, including brain [2,[7][8][9][10], retina [11][12][13], cornea [14] olfactory neuroepithelium [15], pancreas [16], skin [17], muscle [18], bone marrow [19], and embryonic stem cells [20].…”

Section: Introductionmentioning

confidence: 99%

Don't Look: Growing Clonal Versus Nonclonal Neural Stem Cell Colonies

et al. 2008

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Recent reports have challenged the clonality of the neurosphere assay in assessing neural stem cell (NSC) numbers quantitatively. We tested the clonality of the neurosphere assay by culturing mixtures of differently labeled neural cells, watching single neural cells proliferate using video microscopy, and encapsulating single NSCs and their progeny. The neurosphere assay gave rise to clonal colonies when using primary cells plated at 10 cells/l or less; however, when using passaged NSCs, the spheres were clonal only if plated at 1 cell/l. Most important, moving the plates during the growth phase (to look at cultures microscopically) greatly increased the incidence of nonclonal colonies. To ensure clonal sphere formation and investigate nonautonomous effects on clonal sphere formation frequencies, single NSCs were encapsulated in agarose and proliferated as clonal free-floating spheres. We demonstrate that clonal neurospheres can be grown by avoiding movement-induced aggregation, by single-cell tracking, and by encapsulation of single cells. STEM CELLS

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“…More recently, a skeletal muscle precursor population was isolated via FACS sorting CD45 Ϫ , Sca1, Mac1, CXCR4 ϩ , and ␤1 integrin ϩ subpopulations of satellite cells (Cerletti et al, 2008), and a myogenic endothelial cell population in skeletal muscle was initially reported based on CD34 ϩ and CD45 Ϫ expression, which was shown to improve cardiac function after myocardial infarction (Tamaki et al, 2002(Tamaki et al, , 2008a. Tamaki et al (2007Tamaki et al ( , 2008b have also clonally isolated so-called skeletal double-negative cells (Sk-DN), which are CD34 Ϫ /CD45 Ϫ , and have demonstrated their multipotency in vitro and in vivo. Our group has reported a similar population of so-called myoendothelial cells isolated from human skeletal muscle based on their coexpression of CD56, CD34, and CD144 (Zheng et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Levels Represent a Major Determinant in the Regenerative Capacity of Muscle Stem Cells

Urish

Vella

Okada³

et al. 2009

MBoC

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Stem cells are classically defined by their multipotent, long-term proliferation, and self-renewal capabilities. Here, we show that increased antioxidant capacity represents an additional functional characteristic of muscle-derived stem cells (MDSCs). Seeking to understand the superior regenerative capacity of MDSCs compared with myoblasts in cardiac and skeletal muscle transplantation, our group hypothesized that survival of the oxidative and inflammatory stress inherent to transplantation may play an important role. Evidence of increased enzymatic and nonenzymatic antioxidant capacity of MDSCs were observed in terms of higher levels of superoxide dismutase and glutathione, which appears to confer a differentiation and survival advantage. Further when glutathione levels of the MDSCs are lowered to that of myoblasts, the transplantation advantage of MDSCs over myoblasts is lost when transplanted into both skeletal and cardiac muscles. These findings elucidate an important cause for the superior regenerative capacity of MDSCs, and provide functional evidence for the emerging role of antioxidant capacity as a critical property for MDSC survival post-transplantation. INTRODUCTIONMyogenic cell transplantation has been proposed as a promising therapeutic approach in the treatment of skeletal and cardiac muscle injury. Early studies of myoblast transplantation into dystrophic skeletal muscle yielded limited regeneration of dystrophin-expressing muscle fibers (Beauchamp et al., 1994;Gussoni et al., 1997;Qu-Petersen et al., 2002). Similarly, given the limited regenerative ability of cardiac muscle, cell transplantation has been proposed as an alternative to heart transplantation (Assmus et al., 2006;Lunde et al., 2006;Schachinger et al., 2006).A major obstacle in both cardiac and skeletal myogenic therapies is the poor rate of engraftment of myogenic cells after transplantation (Taylor et al., 1998;Oshima et al., 2005). In skeletal muscle, numerous groups have observed a rapid inflammatory response that appears to contribute to rapid cell loss and limit therapeutic success (Beauchamp et al., 1994;Gussoni et al., 1997;Beauchamp et al., 1999). Multiple groups have postulated that the small number of injected cells that survive transplantation in both cardiac and skeletal muscle may represent a special subpopulation of stem-like cells (Qu et al., 1998;Beauchamp et al., 1999;Qu-Petersen et al., 2002).For these reasons, our group attempted to isolate this putative subpopulation of cells using a modified preplate technique. This procedure was initially developed to purify myoblasts from nonmyogenic cells, including fibroblasts, of whole tissue preparations based on the differential adhesion characteristics of the cells to a collagen coated flask (Rando and Blau, 1994). Our group modified this technique to isolate various populations of myogenic cells, including a population of early adhering preplate (EP) cells and a late adhering preplate (LP) cell population from which a subpopulation of long-term proliferating (LTP) cells,...

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Clonal Multipotency of Skeletal Muscle-Derived Stem Cells Between Mesodermal and Ectodermal Lineage

Cited by 69 publications

References 32 publications

Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration

Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration

Don't Look: Growing Clonal Versus Nonclonal Neural Stem Cell Colonies

Antioxidant Levels Represent a Major Determinant in the Regenerative Capacity of Muscle Stem Cells

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