Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications

Tao, Hongyan; Han, Zhibo; Han, Zhong Chao; Li, Zongjin

doi:10.1155/2016/1314709

Cited by 204 publications

(149 citation statements)

References 109 publications

(107 reference statements)

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“…Previous studies have revealed that the myxoma arises from a multipotential endocardial or subendocardial reserve mesenchymal cell which can differentiate into fibrocytes, myocytes, or endothelium [10]. To date, a number of putative markers for mesenchymal stem cells have been reported, including CD44 [11]. Our immunohistology data confirmed the expression of CD44 in myxoma.…”

Section: Resultssupporting

confidence: 82%

Identification of Stem-Like Cells in Atrial Myxoma by Markers CD44, CD19, and CD45

Song

Liu

Cui

et al. 2016

Stem Cells International

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Atrial myxoma is the most frequent tumor arising mainly in atrial septum and its origin remains uncertain. It has been reported that a subpopulation of stem-like cells are present in benign tumors and responsible for tumor initiation and maintenance. In this study, we investigated whether stem-like cells could contribute to the atrial cardiac myxoma. Immunohistology data confirmed that a population of cells bearing the surface markers CD19, CD45, and CD44 resided in a mucopolysaccharide-rich matrix of myxoma. Moreover, we isolated myxoma cells with phase-bright culture method and confirmed that myxoma derived cells express robust level of CD19, CD45, and CD44. Furthermore, the pluripotency of this population of cells also was validated by cardiomyocytes and smooth muscle cells differentiation in vitro. Our results indicate that primary cardiac myxoma may arise from mesenchymal stem cells with the ability to generate tumors with multilineage differentiation. In conclusion, this study for the first time verified that stem-like cells are present in atrial myxoma and this population of cells may have the capacity for myxoma initiation and progression.

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Section: Resultssupporting

confidence: 82%

Identification of Stem-Like Cells in Atrial Myxoma by Markers CD44, CD19, and CD45

Song

Liu

Cui

et al. 2016

Stem Cells International

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“…Such perivascular localization has also been demonstrated for MSCs in several tissues through the body, which support the proposition that MSCs are fundamental to the healing of many tissues. MSCs in the bone marrow are ontogenically distinct populations taking over various biological functions, such as niches for HSCs (6, 12, 13), progenitor cells for bone formation during bone remodeling or repair (14), for cartilage and adipocyte formation, and vascular support (15–17). …”

Section: Mesenchymal Stem Cells or Marrow Stromal Cellsmentioning

confidence: 99%

Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

et al. 2016

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The function of marrow adipocytes and their origin has not been defined although considerable research has centered on their presence in certain conditions, such as osteoporosis. Less work has focused on the qualitative aspects of marrow fat. Bone marrow serum is composed of multiple nutrients that almost certainly relate to functional aspects of the niche. Previous studies using non-invasive techniques have shown that osteoporotic individuals have more marrow fat and that the ratio of saturated: unsaturated fatty acid is high. We recently reported that bone marrow sera from osteoporotic patients with fracture showed a switch toward decreased content of total saturated versus unsaturated fatty acids, compared to patients without fracture highlighting a dynamic relationship between the composition of fatty acids in the bone microenvironment and the metabolic requirements of cells. The relative distribution of fatty acids differed considerably from that in the serum providing further evidence that energy utilization is high and that marrow adipocytes may contribute to this pool. Whether these lipids can affect osteoblast function in a positive or negative manner is still not certain but will require further investigation.

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“…It has been theorized that hMSCs reduce cardiac fibrosis 15 and enhance angiogenesis 16 largely through paracrine signaling (PS) mechanisms. 17,18 Moreover, recent studies have demonstrated that hMSC PS can modulate cardiomyocyte ion channel/pump activity.…”

Section: Introductionmentioning

confidence: 99%

Experimental and Computational Insight Into Human Mesenchymal Stem Cell Paracrine Signaling and Heterocellular Coupling Effects on Cardiac Contractility and Arrhythmogenicity

Mayourian

Cashman

Ceholski

et al. 2017

Circulation Research

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Rationale Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling (HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved. Objective To better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches. Methods and Results Extending our previous hMSC-cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/SERCA activity and cardiac tissue fibrosis. Excitation-contraction simulations of hMSC PS-only and combined HC+PS effects on human cardiomyocytes were representative of human engineered cardiac tissue (hECT) contractile function measurements under matched experimental treatments. Model simulations and hECTs both demonstrated hMSC-mediated effects were most pronounced under PS-only conditions, where developed force increased approximately 4-fold compared to non-hMSC-supplemented controls during physiologic 1-Hz pacing. Simulations predicted contractility of isolated healthy and ischemic adult human cardiomyocytes would be minimally sensitive to hMSC HC, driven primarily by PS. Dominance of hMSC PS was also revealed in simulations of fibrotic cardiac tissue, where hMSC PS protected from potential pro-arrhythmic effects of HC at various levels of engraftment. Finally, to study the nature of the hMSC paracrine effects on contractility, proteomic analysis of hECT/hMSC conditioned media predicted activation of PI3K/Akt signaling, a recognized target of both soluble and exosomal fractions of the hMSC secretome. Treating hECTs with exosomes-enriched, but not exosomes-depleted, fractions of the hMSC secretome recapitulated the effects observed with hMSC conditioned media on hECT developed force and expression of calcium handling genes (e.g., SERCA2a, L-type calcium channel). Conclusions Collectively, this integrated experimental and computational study helps unravel relative hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity, and provides novel insight into the role of exosomes in hMSC paracrine-mediated effects on contractility.

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Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications

Cited by 204 publications

References 109 publications

Identification of Stem-Like Cells in Atrial Myxoma by Markers CD44, CD19, and CD45

Identification of Stem-Like Cells in Atrial Myxoma by Markers CD44, CD19, and CD45

Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

Experimental and Computational Insight Into Human Mesenchymal Stem Cell Paracrine Signaling and Heterocellular Coupling Effects on Cardiac Contractility and Arrhythmogenicity

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