Mesenchymal Stem Cells for Treatment of Myocardial Infarction

Ko, Il-Kwon; Kim, Byung Soo

doi:10.15283/ijsc.2008.1.1.49

Cited by 24 publications

(16 citation statements)

References 34 publications

(40 reference statements)

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“…In the stem cell therapeutic field, adult MSCs have been largely studied with regard to their high self-renewal capacity, differentiation capacity, and low immunogenicity. Among all multipotent MSCs, those derived from bone marrow have recently emerged as an attractive cell type for the treatment of ischemic diseases [ 40 , 41 ]. However, large-scale application of autologous BMSCs still presents challenges because patients can offer only a limited number of BMSCs.…”

Section: Discussionmentioning

confidence: 99%

Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice

et al. 2015

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Introduction‘Patient-specific’ induced pluripotent stem cells (iPSCs) are attractive because they can generate abundant cells without the risk of immune rejection for cell therapy. Studies have shown that iPSC-derived mesenchymal stem cells (iMSCs) possess powerful proliferation, differentiation, and therapeutic effects. Recently, most studies indicate that stem cells exert their therapeutic effect mainly through a paracrine mechanism other than transdifferentiation, and exosomes have emerged as an important paracrine factor for stem cells to reprogram injured cells. The objective of this study was to evaluate whether exosomes derived from iMSCs (iMSCs-Exo) possess the ability to attenuate limb ischemia and promote angiogenesis after transplantation into limbs of mice with femoral artery excision.MethodsHuman iPSCs (iPS-S-01, C1P33, and PCKDSF001C1) were used to differentiate into iMSCs in a modified one-step method. iMSCs were characterized by flow cytometry and multipotent differentiation potential analysis. Ultrafiltration combined with a purification method was used to isolate iMSCs-Exo, and transmission electron microscopy and Western blotting were used to identify iMSCs-Exo. After establishment of mouse hind-limb ischemia with excision of femoral artery and iMSCs-Exo injection, blood perfusion was monitored at days 0, 7, 14, and 21; microvessel density in ischemic muscle was also analyzed. In vitro migration, proliferation, and tube formation experiments were used to analyze the ability of pro-angiogenesis in iMSCs-Exo, and quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay were used to identify expression levels of angiogenesis-related molecules in human umbilical vein endothelial cells (HUVECs) after being cultured with iMSCs-Exo.ResultsiPSCs were efficiently induced into iMSC- with MSC-positive and -negative surface antigens and osteogenesis, adipogenesis, and chondrogenesis differentiation potential. iMSCs-Exo with a diameter of 57 ± 11 nm and expressed CD63, CD81, and CD9. Intramuscular injection of iMSCs-Exo markedly enhanced microvessel density and blood perfusion in mouse ischemic limbs, consistent with an attenuation of ischemic injury. In addition, iMSCs-Exo could activate angiogenesis-related molecule expression and promote HUVEC migration, proliferation, and tube formation.ConclusionImplanted iMSCs-Exo was able to protect limbs from ischemic injury via the promotion of angiogenesis, which indicated that iMSCs-Exo may be a novel therapeutic approach in the treatment of ischemic diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/scrt546) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice

et al. 2015

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“…Over the past decades, there has been tremendous enthusiasm in an attempt to repair cardiac tissue with stem cell transplantation [ 3 ]. Mesenchymal stem cell (MSC), with advantages in immunologic privilege, easy to be acquired, and multilineage potential, has been widely studied both in animal model and in clinical trials [ 4 ]. Low survival rate after transplantation is one of the crucial reasons accounting for the hampered cardiac repair effect of MSC.…”

Section: Introductionmentioning

confidence: 99%

How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

Chen

Wang

et al. 2016

Stem Cells International

174

177

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Mesenchymal stem cell (MSC) is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.

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“…For example, hematopoietic and mesenchymal stem cells are primarily located in bone marrow and peripheral blood (27), neural stem cells are located in ependymal cells and astrocytes (28), and skeletal-muscle stem cells are located in muscle fiber (29).…”

Section: Stem Cells As a Source Of Angiogenesismentioning

confidence: 99%

Clinical Application of Stem Cells for Therapeutic Angiogenesis in Patients with Peripheral Arterial Disease

Lee¹,

Kim²

2009

Int J Stem Cells

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Peripheral arterial disease (PAD) may ultimately cause to the loss of the affected limb due to gangrene or infection. Some patients with PAD may have severe coexisting diseases and diffuse involvement of their distal arteries, and so they are poor candidates for revascularization procedures. Angiogenesis has recently been suggested to be a new emerging treatment strategy for patients with PAD. Angiogenesis is defined as the sprouting of new capillaries from pre-existing vascular structures; this process plays a major role in the development of collateral vessels in an ischemic limb. Yet, the exact mechanism of angiogenesis is currently poorly understood. It has been established that angiogenesis is initiated by hypoxia and it requires various pro-angiogenic factors such as vascular endothelial growth factor. Therapeutic angiogenesis is aimed at enhancing natural angiogenesis by the administration of the cells or genes that can trigger angiogenesis and this can lead to pain relief and wound healing by the development of collateral vessels. Most of the recent clinical trials have reported that stem cell therapy for promoting angiogenesis in patients with PAD improves the ischemic symptoms and enhances wound healing. However, there are several limitations to approve a standard treatment for PAD such as small sample size in several prevous studies, their diverse inclusion criteria and the lack of standard assessment methods for the safety and outcome. Therefore, multicenter, large-scale and randomized controlled studies are needed to prove the safety and efficacy of the clinically applying stem cells for therapeutic angiogenesis in patients with PAD.

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Mesenchymal Stem Cells for Treatment of Myocardial Infarction

Cited by 24 publications

References 34 publications

Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice

Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice

How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

Clinical Application of Stem Cells for Therapeutic Angiogenesis in Patients with Peripheral Arterial Disease

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