C-Kit Positive Cardiac Stem Cells and Bone Marrow–Derived Mesenchymal Stem Cells Synergistically Enhance Angiogenesis and Improve Cardiac Function After Myocardial Infarction in a Paracrine Manner

Bao, Luer; Meng, Qingshu; Li, Yuan; Deng, Shengqiong; Yu, Zuoren; Liu, Zhongmin; Zhang, Lin; Fan, Huimin

doi:10.1016/j.cardfail.2017.03.002

Cited by 57 publications

(50 citation statements)

References 47 publications

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“…In ACCT only, this reduction was accompanied by improvements in perfusion in the infarct zone as compared to placebo. This result suggests that as scar size is diminished, perfusion increases to areas that were previously infarcted, possibly through paracrine stimulation of angiogenesis (9,22,39,40). Furthermore, only the ACCT treatment halted the progression of negative remodeling, whereas it continued to worsen significantly in the placebo, CSC and MSC groups.…”

Section: Discussionmentioning

confidence: 94%

“…The increased regenerative capacity of combination therapy secondary to direct cell-cell signaling in the stem cell niche was reinforced by Quijada et al who demonstrated that chimeras of cardiac progenitor cells and MSCs produce superior therapeutic efficacy in a mouse model of MI (38). Finally, a recent rat study showed that the combination of allo-CSCs and allo-MSCs improve angiogenesis via paracrine signaling better than either cell type alone (39). …”

Section: Discussionmentioning

confidence: 99%

“…Enhancement of cardiomyocyte and non-cardiomyocyte mitoses in ACCT, as evaluated by pHH3 staining, may contribute to the improved contractility. Cardiomyocyte proliferation significantly increased in the ACCT group only in the remote zone, which may be secondary to the paracrine effects of both MSCs and CSCs (39). Furthermore, the inhibition of progressive negative remodeling, which is global, may involve cardiomyocyte mitosis in areas distant from the scar and injection sites.…”

Section: Discussionmentioning

confidence: 99%

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A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration

Natsumeda

Florea

Rieger

et al. 2017

Journal of the American College of Cardiology

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Background The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT). Objective We tested the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions. Methods Gottingen swine with experimental ischemic cardiomyopathy were randomized to receive transendocardial injections of either allo-MSC + allo-CSC (ACCT: 200 million MSCs/1 million CSCs, n=7), 200 million allo-MSC (n=8), 1 million allo-CSC (n=4), or placebo (Plasma-Lyte A, n=6)]. Swine were assessed by cardiac magnetic resonance imaging (cMR) and pressure volume catheterization. Immune response was tested by histological analyses. Results Both ACCT and allo-MSCs reduced scar size by −11.1±4.8%, (p=0.012) and −9.5±4.8 (p=0.047), respectively. Only ACCT, but not MSC or CSC, prevented ongoing negative remodeling by offsetting increases in chamber volumes. Importantly, ACCT exerted the greatest effect on systolic function, improving the end-systolic pressure volume relation (+0.98±0.41 mmHg/mL, p=0.016) The ACCT group had more phospho-histone H3 (pHH3)+ (a marker of mitosis) cardiomyocytes (p=0.04), and non-cardiomyocytes (p=0.0002) compared to the placebo group in some regions of the heart. Inflammatory sites in ACCT and MSC swine contained immunotolerant CD3+/CD25+/FoxP3 regulatory T cells (p<0.0001). Histologic analysis showed absent to low grade inflammatory infiltrates without cardiomyocyte necrosis. Conclusion ACCT demonstrates synergistic effects to enhance cardiac regeneration and left ventricular functional recovery in a swine model of chronic ischemic cardiomyopathy without adverse immunological reaction. Clinical translation to humans is warranted.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration

Natsumeda

Florea

Rieger

et al. 2017

Journal of the American College of Cardiology

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“…MSCs secrete VEGF, FGF, HGF, placental growth factor (PGF), monocyte chemotactic protein 1 (MCP-1), stromal cell-derived factor 1 (SDF-1), and angiopoietin-1 (Ang-1) that are critical for vascularization [178][179][180][181][182][183]. Several studies have reported the potential of increasing capillaries and newly formed vessels following MSC administration both in vitro and in vivo [184][185][186].…”

Section: Angiogenic Factorsmentioning

confidence: 99%

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

343

282

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Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies. Keywords Regenerative potential • Integration of MSCs • Immunomodulation • Soluble factors • Cell-cell contact • Mitochondrial transfer • Extracellular vesicles Abbreviations AHR Airway hyper-responsiveness Alix ALG-2-interacting protein X Ang-1 Angiopoietin-1 ASCs Adipose-derived stem cells BAX BCL-2-associated X protein BCL-2 B-cell lymphoma 2 CASP3 Caspase 3 CX43 Connexin 43 CXCR4 Chemokine receptor type 4 DC Dendritic cell Cellular and Molecular Life Sciences

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“…As a result, transplantation of these HF CDS into infarcted mice hearts increased the proliferation rate of endogenous endothelial cells by ~30% in comparison to control CDCs [291]. Similarly, rat c-kit + CSCs significantly improved angiogenesis post MI in a paracrine manner by the secretion of VEGF [297].…”

Section: Neovascularizationmentioning

confidence: 86%

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Müller

Lemcke

Dávid

2018

Cell Physiol Biochem

161

140

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A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the “next generation” of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach.

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C-Kit Positive Cardiac Stem Cells and Bone Marrow–Derived Mesenchymal Stem Cells Synergistically Enhance Angiogenesis and Improve Cardiac Function After Myocardial Infarction in a Paracrine Manner

Cited by 57 publications

References 47 publications

A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration

A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

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