Stem cell therapy for acute myocardial infarction - focusing on the comparison between Muse cells and mesenchymal stem cells.

Rapid percutaneous coronary intervention for acute myocardial infarction (AMI) reduces acute mortality, but there is an urgent need for treatment of left ventricular dysfunction and remodeling after AMI to improve the prognosis. The myocardium itself does not have a high regenerative capacity, and it is important to minimize the loss of cardiomyocytes and maintain the cardiac function after AMI. To overcome these problems, attention has been focused on myocardial regeneration therapy using cells derived from bone marrow. The clinical use of bone marrow stem cells is considered to have low safety concerns based on the experience of using bone marrow transplantation for blood diseases in clinical practice. It has been reported that bone marrow mononuclear cells (BM-MNC) and mesenchymal stem cells (BM-MSC) differentiate into cardiomyocytes both in vitro and in vivo, and they have been considered a promising source for stem cell therapy. To prevent heart failure after human AMI, studies have been conducted to regenerate myocardial tissue by transplanting bone marrow stem cells, such as BM-MSCs and BM-MNCs. Therapies using those cells have been administered to animal models of AMI, and were effective to some extent, but the effect in clinical trials was limited. Recently, it was reported that multilineage-differentiating stress enduring cells (Muse cells), which are endogenous pluripotent stem cells obtainable from various tissues including the bone marrow, more markedly reduced the myocardial infarct size and improved the cardiac function via regeneration of cardiomyocytes and vessels and paracrine effects compared with BM-MSCs. Here, we describe stem cell therapies using conventional BM-MNCs and BM-MSCs, and Muse cells which have potential for clinical use for the treatment of AMI.

Yamada Y ，Minatoguchi S ，Kanamori H ，Mikami A ，Okura H ，Dezawa M ，Minatoguchi S ... -  《-》

Mechanisms of improvement of left ventricle remodeling by trans-planting two kinds of autologous bone marrow stem cells in pigs.

Li SR ，Qi XY ，Hu FL ，Zhang JQ ，Wang TH ，Dang Y ，Meng CL ，Liu HL ，Li YX ，Wu D ，Dong J ，Xun LY ，Gao LH ，Jin FC ... -  《-》

Comparing the effect of bone marrow mono-nuclear cells with mesenchymal stem cells after acute myocardial infarction on improvement of left ventricular function: a meta-analysis of clinical trials.

The effect of transplantation of bone-marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs) on ejection fraction (LVEF) has been studied in patients with acute myocardial infarction (AMI) in clinical trials. This raises the question that which type of cell may help improve LVEF better in AMI patients. No meta-analysis of clinical trials has yet addressed this question. Electronic databases were searched thoroughly to find eligible trials on the effects of transplantation of BM-MNCs and MSCs in patients with AMI. The primary outcome was improvement in LVEF. Data were synthesized using random-effects meta-analysis. For maximizing the credibility of subgroup analysis, we used the instrument for assessing the Credibility of Effect Modification of Analyses (ICEMAN) for meta-analyses. A total of 36 trials (26 on BM-MNCs and 10 on MSCs) with 2489 patients (1466 were transplanted [1241 with BM-MNCs and 225 with MSCs] and 1023 as controls) were included. Both types of cells showed significant improvements in ejection fraction in short-term follow-up (BM-MNCs: WMD = 2.13%, 95% CI = 1.23 to 3.04, p < 0.001; MSCs: WMD = 3.71%, 95% CI = 2.32 to 5.09, p < 0.001), and according to ICEMAN criteria, MSCs are more effective. For selected population of patients who received stem cell transplantation in early course after AMI (less than 11 days), this effect was even more pronounced (BM-MNC: WMD = 3.07%, 95% CI = 1.97 to 4.17, p < 0.001, I2 = 40.7%; MSCs: WMD = 5.65%, 95% CI = 3.47 to 7.84, p < 0.001, I2 = 84.6%). Our results showed that transplantation of MSCs after AMI might increase LVEF more than BM-MNCs; also, based on ICEMAN, there was likely effect modification between subgroups although uncertainty still remained.

Hosseinpour A ，Kheshti F ，Kazemi A ，Attar A ... -  《Stem Cell Research & Therapy》

Acute Myocardial Infarction, Cardioprotection, and Muse Cells.

Minatoguchi S ，Mikami A ，Tanaka T ，Minatoguchi S ，Yamada Y ... -  《-》

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.

Stem cell transplantation offers a promising treatment for heart failure. Recent studies show that both c-kit positive cardiac stem cells (CSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) are good candidates for stem cell therapy to treat heart failure; however, the exact mechanism of stem cell therapy in improving cardiac function of ischemic cardiomyopathy is not fully known. Our objective was to test our hypothesis that CSCs and/or BM-MSCs repair the damaged heart by boosting post-myocardial infarction (MI) angiogenesis in a paracrine manner. We isolated and purified CSCs and BM-MSCs from rats. Intramyocardial injections of CSCs and/or BM-MSCs were performed at 28 days after MI. We applied cardiac ultrasound and histological analysis to evaluate the effect of cell therapy on cardiac function and cardiac remodeling. In vivo donor cell transplantation experiments showed that CSCs and/or BM-MSCs improved cardiac function after MI and reduced infarct size. However, in vivo cell tracking experiments showed that minimal donor cells remained in the myocardium after cell transplantation. Our further in vitro and in vivo experiments showed that transplantation of CSCs enhanced the expression of pro-angiogenic factors and boosted post-MI angiogenesis in the myocardium in a paracrine manner, which in part contributed to the effect of CSCs on cardiac recovery after MI. CSCs and BM-MSCs synergistically inhibited CSC/BM-MSC apoptosis and enhanced their proliferation in a paracrine manner. This resulted in a larger number of transplanted cells remaining in the post-MI myocardium after coinjection of CSCs and BM-MSCs, and therefore the accumulation of more pro-angiogenic factors in the heart tissue compared to transplantation of CSCs or MSCs alone. Consequently, transplantation of both CSCs and BM-MSCs was superior to transplantation of either CSCs or BM-MSCs alone to boost post-MI angiogenesis and improve cardiac function after MI. C-kit+ CSC and/or BM-MSC transplantation can improve cardiac function after MI in a paracrine manner. Coinjection of both CSCs and BM-MSCs improves cardiac function more significantly than CSC or BM-MSC transplantation alone in a paracrine manner by improving the engraftment of donor cells and boosting the expression of multiple pro-angiogenic factors.

Bao L ，Meng Q ，Li Y ，Deng S ，Yu Z ，Liu Z ，Zhang L ，Fan H ... -  《-》