Transplantation of Mesenchymal Stem Cells Improves Cardiac Function in a Rat Model of Dilated Cardiomyopathy

Nagaya, Noritoshi; Kangawa, Kenji; Itoh, Takefumi; Igarashi, Takashi; Murakami, Shigetaka; Miyahara, Yoshinori; Fujii, Takafumi; Uematsu, Masaaki; Ohgushi, Hajime; Yamagishi, Masakazu; Tokudome, Takeshi; Mori, Hiromu; Miyatake, Kunio; Kitamura, Soichiro

doi:10.1161/circulationaha.104.500447

Cited by 604 publications

(484 citation statements)

References 55 publications

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“…Furthermore transplanted MSCs improved cardiac function in dilated cardiomyopathy (26). For that reason, we speculated that MSCs may differentiate into multiple skin cell types during wound healing.…”

Section: Mscs Differentiate Into Multiple Skin Cell Typesmentioning

confidence: 97%

Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

Sasaki

Abe

Fujita

et al. 2008

The Journal of Immunology

894

696

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Mesenchymal stem cells (MSCs) can differentiate not only into mesenchymal lineage cells but also into various other cell lineages. As MSCs can easily be isolated from bone marrow, they can be used in various tissue engineering strategies. In this study, we assessed whether MSCs can differentiate into multiple skin cell types including keratinocytes and contribute to wound repair. First, we found keratin 14-positive cells, presumed to be keratinocytes that transdifferentiated from MSCs in vitro. Next, we assessed whether MSCs can transdifferentiate into multiple skin cell types in vivo. At sites of mouse wounds that had been i.v. injected with MSCs derived from GFP transgenic mice, we detected GFP-positive cells associated with specific markers for keratinocytes, endothelial cells, and pericytes. Because MSCs are predominantly located in bone marrow, we investigated the main MSC recruitment mechanism. MSCs expressed several chemokine receptors; especially CCR7, which is a receptor of SLC/CCL21, that enhanced MSC migration. Finally, MSC-injected mice underwent rapid wound repaired. Furthermore, intradermal injection of SLC/CCL21 increased the migration of MSCs, which resulted in an even greater acceleration of wound repair. Taken together, we have demonstrated that MSCs contribute to wound repair via processes involving MSCs differentiation various cell components of the skin.

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Section: Mscs Differentiate Into Multiple Skin Cell Typesmentioning

confidence: 97%

Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

Sasaki

Abe

Fujita

et al. 2008

The Journal of Immunology

894

696

View full text Add to dashboard Cite

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“…First promising results for stem cell therapy in nonischemic dilated cardiomyopathy (DCM) were reported by Nagaya et al (120). The aim of the study was to investigate whether transplanted mesenchymal stem cells (MSCs) induce myogenesis and angiogenesis in a rat model of DCM.…”

Section: Dilated Cardiomyopathymentioning

confidence: 99%

Endothelial progenitor cells: Implications for cardiovascular disease

et al. 2008

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“…Furthermore, the accessibility, ease of handling, and enormous expansion potential of MSCs, together with their capacity for self-renewal and amenability to allogenic transplantation (Amado et al, 2005;Dai et al, 2005), provide a nearly unlimited supply of cells for therapeutic applications. The effect of MSCs is thought to be mediated by secreting a number of cardio-protective cytokines and growth factors in addition to differentiation (Kinnaird et al, 2004a(Kinnaird et al, , 2004bNagaya et al, 2005). Despite initial optimism, MSC transplant therapy has been stymied by the low cellular survival rate after transplantation in the first few days (Toma et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

et al. 2011

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Bone marrow mesenchymal stem cells (MSCs) are considered as a promising cell source to treat the acute myocardial infarction. However, over 90% of the stem cells usually die in the first three days of transplantation. Survival potential, migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment. We hypothesized that stromal-derived factor-1 (SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes. In this study, apoptosis was induced by exposure of MSCs to H 2 O 2 for 2 h. After re-oxygenation, the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation. SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor. Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio. These protective effects were partially inhibited by AMD3100, an antagonist of CXCR4. We conclude that the SDF-1/CXCR4 axis is critical for MSC survival, migration and cytokine secretion.

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Transplantation of Mesenchymal Stem Cells Improves Cardiac Function in a Rat Model of Dilated Cardiomyopathy

Abstract: Background-Pluripotent

Cited by 604 publications

References 55 publications

Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

Endothelial progenitor cells: Implications for cardiovascular disease

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

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