Percutaneous Intramyocardial Delivery of Mesenchymal Stem Cells Induces Superior Improvement in Regional Left Ventricular Function Compared with Bone Marrow Mononuclear Cells in Porcine Myocardial Infarcted Heart

Tao, Bo; Ming-liang, Cui; Wang, Chen; Ma, Sai; Wu, Feng; Yi, Fu; Qin, Xing; Liu, Junting; Wang, Haichang; Wang, Zhe; Ma, Xiaowei; Hui, Hui; Chen, Yundai; Wang, Jing; Cao, Feng

doi:10.7150/thno.7976

Cited by 38 publications

(26 citation statements)

References 30 publications

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“…In a swine acute-MI model, Tao et al (352) found that autologous bone marrow-derived MSCs engrafted within the ischemic myocardium at week 3 but not at week 10 post-injection (352). Analogously, immunohistochemistry studies against In fact, an intravenous approach to cellular delivery has been to shown to result in insufficient MSC engraftment (150), and intramyocardial administration may be more superior to the intravenous or intracoronary routes (103).…”

Section: A Engraftment Differentiation and Fusionmentioning

confidence: 94%

Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

Golpanian

Wolf

Hatzistergos

et al. 2016

Physiological Reviews

274

211

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Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise. Numerous preclinical studies of ischemic and nonischemic cardiomyopathy employing MSC-based therapy have demonstrated that the properties of reducing fibrosis, stimulating angiogenesis, and cardiomyogenesis have led to improvements in the structure and function of remodeled ventricles. Further attempts have been made to augment MSCs' effects through genetic modification and cell preconditioning. Progression of MSC therapy to early clinical trials has supported their role in improving cardiac structure and function, functional capacity, and patient quality of life. Emerging data have supported larger clinical trials that have been either completed or are currently underway. Mechanistically, MSC therapy is thought to benefit the heart by stimulating innate anti-fibrotic and regenerative responses. The mechanisms of action involve paracrine signaling, cell-cell interactions, and fusion with resident cells. Trans-differentiation of MSCs to bona fide cardiomyocytes and coronary vessels is also thought to occur, although at a nonphysiological level. Recently, MSC-based tissue engineering for cardiovascular disease has been examined with quite encouraging results. This review discusses MSCs from their basic biological characteristics to their role as a promising therapeutic strategy for clinical cardiovascular disease.

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Section: A Engraftment Differentiation and Fusionmentioning

confidence: 94%

Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

Golpanian

Wolf

Hatzistergos

et al. 2016

Physiological Reviews

274

211

View full text Add to dashboard Cite

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“…Stem cell transplantation has therapeutic effects on AMI [37, 38]. However, due to changes in the myocardial tissue environment after ischaemia, the function of the transplanted cells is restricted.…”

Section: Discussionmentioning

confidence: 99%

Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury

Luo¹,

Guo²,

Liu³

et al. 2017

Cell Physiol Biochem

229

158

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Background/Aims: Recent studies have indicated that exosomes play an important role in adipose-derived stem cell (ADSC) transplant-mediated ischaemic heart disease therapy. However, the treatment effect is not obvious. The aim of this study is to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-126 have a more protective effect on acute myocardial infarction (AMI). Methods: Exosomes were characterized by transmission electron microscopy, and the exosome particles were further examined using nanoparticle tracking analyses. A rat model of myocardial infarction and in vitro model of hypoxia-induced H9c2 myocardial cell injury were established to study the protective mechanism of exosomes from miR-126-overexpressing ADSCs. Results: The in vitro results showed that exosomes derived from miR-126-overexpressing ADSCs decreased H9c2 myocardial cell injury by reducing inflammation factor expression during hypoxia induction. The miR-126-enriched exosomes also decreased the expression of fibrosis-related proteins of H9c2 cells under hypoxic conditions. Matrigel® and Transwell® assays showed that miR-126-enriched exosomes significantly promoted microvascular generation and migration, respectively. In vivo studies confirmed that exosomes derived from ADSCs significantly decreased the myocardial injury area of infarction, especially after miR-126-enriched exosome treatment. Cardiac fibrosis and inflammatory cytokine expression were also decreased after treatment with miR-126-enriched exosomes. However, blood vessel formation was promoted in the infarction region of AMI rats. Conclusions: The results suggested that the expression of miR-126-enhanced ADSC-derived exosomes prevented myocardial damage by protecting myocardial cells from apoptosis, inflammation, fibrosis, and increased angiogenesis.

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“…A previous meta-analysis of large animal models (such as pigs, dogs, and sheep) of MI indicated that the transplantation of BM-MSCs led to a significant improvement of left ventricle ejection fraction. In addition, a trend toward greater advantage in the case of administration of MSCs when compared with BM-MNCs was reported (32,33).…”

Section: Figmentioning

confidence: 97%

Comparing the effects of MSCs and CD34+ cell therapy in a rat model of myocardial infarction

et al. 2016

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Stem cell therapy is considered as a promising approach in the treatment of myocardial infarction (MI). This study was designed as a comparison of human umbilical cord blood (HUCB)-derived CD341 and HUCB-derived MSCs for the repair of cardiac tissue by induction of the angiogenesis. Forty-eight male rats were randomized into four groups: sham-operated group, MI group, MSCs-treated group, and CD341 cellstreated group. After 4 weeks, the rats were sacrificed. All sections from left ventricles of all groups were subjected to hematoxylin & eosin, Masson's trichrome, and immunohistochemical stains (CD133, CD44, and a-smooth muscle actin). RNA was extracted for gene expression of the angiogenic markers. A significant reduction of the infarct size and the amplitude of T-wave in the CD341 cells-treated group when compared with the MSCs-treated group were determined. Histologically, the MI group showed scar tissue, congested blood capillaries around the infarcted area, some necrotic cells, and inflammatory cells. Administration of either MSCs or CD341 cells had a therapeutic potential to induce regenerative changes in the myocardium with better results in CD341cells-treated group. Quantitative RT-PCR analysis revealed a significant increase in the expression of vascular endothelial growth factor (VEGF), VEGFR-2, Ang-1, and Tie-2 and a significant decreased expression of Ang-2 in stem cells transplanted groups when compared with the noncell transplanted hearts. A significant increase of VEGF, VEGFR-2, Ang-1, and Tie-2 expression in the group receiving CD341 cells than those receiving MSCs was found. Finally, there was an upregulation of both human VEGF and human hypoxia-inducible factor 1a in the infarcted hearts treated by CD341 cells than that treated by MSCs. We first revealed a superior efficacy of CD341 cells when compared with MSCs in induction of regenerative changes in the MI model. Both cell therapies may repair the damaged heart tissue primarily by secretion of proangiogenic factors that induce the angiogenesis and activate the angiogenesis signaling pathway. V C 2016 IUBMB Life, 68(5): [343][344][345][346][347][348][349][350][351][352][353][354] 2016

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Percutaneous Intramyocardial Delivery of Mesenchymal Stem Cells Induces Superior Improvement in Regional Left Ventricular Function Compared with Bone Marrow Mononuclear Cells in Porcine Myocardial Infarcted Heart

Cited by 38 publications

References 30 publications

Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury

Comparing the effects of MSCs and CD34+ cell therapy in a rat model of myocardial infarction

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