Cardiomyocyte Formation by Skeletal Muscle-Derived Multi-Myogenic Stem Cells after Transplantation into Infarcted Myocardium

Tamaki, Toru; Akatsuka, Akira; Okada, Yoshinori; Uchiyama, Yoshiyasu; Tono, Kayoko; Wada, Mika; Hoshi, Akio; Iwaguro, Hideki; Iwasaki, Hiroto; Oyamada, Akira; Asahara, Takayuki

doi:10.1371/journal.pone.0001789

Cited by 42 publications

(53 citation statements)

References 34 publications

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“…Previous studies have shown that stem cells isolated from skeletal muscle specimens have the ability to differentiate into CMs; 8,14,[16][17][18][19] however, the efficiency of CM differentiation remains unclear and with limited functional characterization. In the current study we found that (1) low-serum growth medium-treated rat MDSCs expressed cardiacspecific genes similar to native adult myocardium, consistent with the findings of others in both human and mouse skeletal muscle-derived cells, and (2) the combination of MDSC-aggregate formation and 3DGB culture significantly increased cardiac-specific protein expression, spontaneous beating cell activity, and contractile properties.…”

Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Gel Bioreactor for Assessment of Cardiomyocyte Induction in Skeletal Muscle–Derived Stem Cells

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Tinney

Liu

et al. 2010

Tissue Engineering Part C: Methods

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Skeletal muscle-derived stem cells (MDSCs) are able to differentiate into cardiomyocytes (CMs). However, it remains to be investigated whether differentiated CMs contract similar to native CMs. Here, we developed a three-dimensional collagen gel bioreactor (3DGB) that induces a working CM phenotype from MDSCs, and the contractile properties are directly measured as an engineered cardiac tissue. Neonate rat MDSCs were isolated from hind-leg muscles via the preplate technique. Isolated MDSCs were approximately 60% positive to Sca-1 and negative to CD34, CD45, or c-kit antigens. We sorted Sca-1(À) MDSCs and constructed MDSC-3DGBs by mixing MDSCs with acid soluble rat tail collagen type-I and matrix factors. MDSC-3DGB exhibited spontaneous cyclic contraction by culture day 7. MDSC-3DGB expressed cardiac-specific genes and proteins. Histological assessment revealed that cardiac-specific troponin-T and -I expressed in a typical striation pattern and connexin-43 was expressed similar to the native fetal ventricular papillary muscle. b-Adrenergic stimulation increased MDSC-3DGB spontaneous beat frequency. MDSC-3DGB generated contractile force and intracellular calcium ion transients similar to engineered cardiac tissue from native cardiac cells. Results suggest that MDSC-3DGB induces a working CM phenotype in MDSCs and is a useful 3D culture system to directly assess the contractile properties of differentiated CMs in vitro.

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Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Gel Bioreactor for Assessment of Cardiomyocyte Induction in Skeletal Muscle–Derived Stem Cells

Clause

Tinney

Liu

et al. 2010

Tissue Engineering Part C: Methods

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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.…”

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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“…Alternatively, skeletal myoblast engraftment may be combined with bone marrow stem cell transplantation for mutual beneficial effect of the two cell types (71). Studies are already underway to subfractionate and purify more primitive populations from the two cell types and showing multilineage differentiation potential, including cardiac lineage (114).…”

Section: Adult Stem Cells In Cardiovascular Therapymentioning

confidence: 99%

De NovoMyocardial Regeneration: Advances and Pitfalls

Haider

Buccini

Ahmed

et al. 2010

Antioxidants & Redox Signaling

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The capability of adult tissue-derived stem cells for cardiogenesis has been extensively studied in experimental animals and clinical studies for treatment of postischemic cardiomyopathy. The less-than-anticipated improvement in the heart function in most clinical studies with skeletal myoblasts and bone marrow cells has warranted a search for alternative sources of stem cells. Despite their multilineage differentiation potential, ethical issues, teratogenicity, and tissue rejection are main obstacles in developing clinically feasible methods for embryonic stem cell transplantation into patients. A decade-long research on embryonic stem cells has paved the way for discovery of alternative approaches for generating pluripotent stem cells. Genetic manipulation of somatic cells for pluripotency genes reprograms the cells to pluripotent status. Efforts are currently focused to make reprogramming protocols safer for clinical applications of the reprogrammed cells. We summarize the advancements and complicating features of stem cell therapy and discuss the decade-and-a-half-long efforts made by stem cell researchers for moving the field from bench to the bedside as an adjunct therapy or as an alternative to the contemporary therapeutic modalities for routine clinical application. The review also provides a special focus on the advancements made in the field of somatic cell reprogramming.

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Cardiomyocyte Formation by Skeletal Muscle-Derived Multi-Myogenic Stem Cells after Transplantation into Infarcted Myocardium

Cited by 42 publications

References 34 publications

A Three-Dimensional Gel Bioreactor for Assessment of Cardiomyocyte Induction in Skeletal Muscle–Derived Stem Cells

A Three-Dimensional Gel Bioreactor for Assessment of Cardiomyocyte Induction in Skeletal Muscle–Derived Stem Cells

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

De NovoMyocardial Regeneration: Advances and Pitfalls

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