Mesenchymal Stem/Stromal Cell-Based Therapy for Heart Failure　― What Is the Best Source? ―

Abstract

Transplantation of stem/progenitor cells is a promising, emerging treatment for heart failure (HF) in the modern era. Mesenchymal stem/stromal cells (MSCs) are considered as one of the most promising cell sources for this purpose, because of their powerful secretion of reparative factors and immunomodulatory ability. To date, various sources of MSCs have been examined for the treatment of HF in preclinical or clinical studies, including adult tissues (bone marrow and adipose tissue), perinatal tissues (umbilical cord and amnion), and pluripotent stem cells (induced pluripotent stem cells and embryonic stem cells). Adult tissue-derived MSCs have been more extensively examined. Previous clinical trials have suggested the safety and feasibility of these MSCs in HF treatment, but their therapeutic effects remain arguable. Perinatal tissue-derived MSCs have the advantages of removing the necessity of invasiveness biopsy and of mass production. An increasing number of clinical studies (albeit early stage) have been conducted. Pluripotent stem cell-derived MSCs may be another promising source because of their mass-production ability underpinned by their unlimited expansion with consistent quality. However, the risk of tumorigenicity restricts their clinical application. In this review, we summarize the current information available from preclinical and clinical studies, highlighting the advantages and disadvantages of each MSC type. This will provide an insight into consideration of the best MSC source for the treatment of HF.

Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice

“… 51 Indeed, MSCs secrete a variety of bioactive molecules, such as cytokines, chemokines, growth factors, and exosomes. 52 In our study, we used a systemic injection of hMSCs and confirmed that the vast majority of them accumulated in the lung. 34 , 35 Hence, the effects of hMSCs are supposed to mainly rely on paracrine-secreting mediators.…”

Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, randomized controlled muticentre trial

“…In clinic, Autologous bone marrow MSCs have been expanded in vitro and transplanted to treat myocardial infarction [7] . However, reviewing the clinical study of BM-MSCs on AMI from 2004 to 2017, it was found that compared with the control group, only two clinical research results showed that BM-MSCs can increase the left ventricular ejection fraction of patients [21] .Our research aims to conduct a randomized, single-blind, parallel-controlled multicenter clinical trial using BM-MSCs injection with independent intellectual property rights in China. It is hoped that this study will show whether BM-MSCs injection transplantation is effective and safe in patients with ST-segment elevation myocardial infarction(STEMI), and provide a reliable basis for clinical promotion.…”

Mesenchymal stem cells from human amniotic membrane differentiate into cardiomyocytes and endothelial-like cells without improving cardiac function after surgical administration in rat model of chronic heart failure

“…Mesenchymal stem cells (MSCs) have gained popularity for their use in myocardial regeneration. 11 According to the International Society for Cellular Therapy (ISCT) minimal criteria for defining the multipotent MSCs, these are plastic-adherent cells, expressing CD105, CD73 and CD90 markers and lacking the surface presentation of CD45, CD34, CD14 or CD11b, CD79a or CD19 and HLA-DR markers. Moreover, they have the capacity for in vitro differentiation to osteoblasts, adipocytes and chondroblasts.…”

“…16-24 These cells help improve tissue hemostasis through modulating the immune response and improving blood flow by angiogenesis induction and sparing the existing cardiomyocytes from apoptotic and necrotic cell death. 11,13,14,25 Therefore, studying their applicability in chronic ischemic HF, where severe inflammatory response and myocardial cell death have led to tissue remodeling and tissue fibrosis, is required.…”