Enhancement Strategies for Cardiac Regenerative Cell Therapy

Broughton, Kathleen M.; Sussman, Mark A.

doi:10.1161/circresaha.118.311207

Cited by 26 publications

(20 citation statements)

References 98 publications

(112 reference statements)

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“…Over the past decade, pioneering preclinical research into the use of cell therapy for cardiac regeneration has been completed [20]. However, cell therapy remains challenging for a number of reasons including the selection of cell types, the minimal potency of injected cells, and the limited engraftment and retention of administered cells [20][21][22]. A recent study demonstrated that although transplanted, cells could not differentiate into cardiac myocytes [23].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis

Cheng

Chang

et al. 2020

Preprint

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Background Myocardial infarction (MI) is a major cause of death worldwide. Although percutaneous coronary intervention and coronary artery bypass grafting can prolong life, cardiac damage persists. In particular, cardiomyocytes have no regenerative capacity. Mesenchymal stem cells (MSCs) are attractive candidates for the treatment of MI. The manner by which MSCs exert a beneficial effect upon injured cells is a source of continued study. Methods After the isolation and identification of exosomes from MSCs, the expression of miR-210 was determined by Microarray Chip. Subsequently, gain- and loss-function approaches were conducted to detect the role of exosomes and exosomal-miR-210 in cell proliferation and apoptosis of cardiomyocytes, as well as the MI in vivo . Dual-Luciferase Report Gene System was used to demonstrate the target gene of miR-210. Results We tested the hypothesis that MSC-derived exosomes transfer specific miRNA to protect cardiomyocytes from apoptotic cell death. Interestingly, direct cardiac injection of MSC exosomes reduced infarct size and improved heart function after coronary ligation. In vitro , the MSC exosomes enhanced cardiomyocyte survival to hypoxia. Confirmation of exosome uptake in myocytes was confirmed. Dual luciferase reporter assay implicated miR-210 as a mediator of the therapeutic effect and AIFM3 as a downstream target. Treatment with miR-210 overexpressing MSC exosomes improved myocyte protection to both in vitro and in vivo stress. Furthermore, the endogenous and exogenous miR-210 had the same therapeutic effects. Conclusion These results demonstrated that the beneficial effects offered by MSC-exosomes transplantation after MI are at least partially because of excreted exosome containing mainly miR-210.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis

Cheng

Chang

et al. 2020

Preprint

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“…Upon transplantation, the stem cells are confronted with a harsh environment at the MI site, which results in a lower engraftment rate, poor survival, and weak proliferative abilities, therefore limiting the effectiveness of the therapy [ 33 ]. The in vitro preconditioning of stem cells aims to prepare the cells for the ischemic environment prior to transplantation and is among the possible solutions that have demonstrated significant enhancement in infarction site recovery [ 34 , 35 ]. The cells can be preconditioned via various methods, including but not limited to pretreatment with hypoxia, drugs, biological agents, and growth factors ( Figure 1 ) [ 31 , 36 , 37 ].…”

Section: Stem Cell Preconditioning For MI Treatmentmentioning

confidence: 99%

Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

Raziyeva

Smagulova

Kim

et al. 2020

IJMS

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Ischemic heart disease and myocardial infarction remain leading causes of mortality worldwide. Existing myocardial infarction treatments are incapable of fully repairing and regenerating the infarcted myocardium. Stem cell transplantation therapy has demonstrated promising results in improving heart function following myocardial infarction. However, poor cell survival and low engraftment at the harsh and hostile environment at the site of infarction limit the regeneration potential of stem cells. Preconditioning with various physical and chemical factors, as well as genetic modification and cellular reprogramming, are strategies that could potentially optimize stem cell transplantation therapy for clinical application. In this review, we discuss the most up-to-date findings related to utilizing preconditioned stem cells for myocardial infarction treatment, focusing mainly on preconditioning with hypoxia, growth factors, drugs, and biological agents. Furthermore, genetic manipulations on stem cells, such as the overexpression of specific proteins, regulation of microRNAs, and cellular reprogramming to improve their efficiency in myocardial infarction treatment, are discussed as well.

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“…SCASCs generated from bone marrow are known as bone-marrow SCs, 37 having clinical significance in restoring damaged cardiac tissue through gene therapy. 70 Also, they can be a potential source for auto-HSCT.. 37 There is an improvement in GVHD in patients with bone-marrow SC transplantation compared to peripheral blood SCs (PBSCs). 19 Bone marrow–SC transplantation is utilized in various hematologic malignancies, such as AML, ALL, and CML.…”

Section: Bone-marrow Stem Cells As Source For Stem-cell Transplantatimentioning

confidence: 99%

<p>Role of Stem-Cell Transplantation in Leukemia Treatment</p>

Dessie¹,

Molla²,

Shibabaw³

et al. 2020

SCCAA

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Stem cells (SCs) play a major role in advanced fields of regenerative medicine and other research areas. They are involved in the regeneration of damaged tissue or cells, due to their self-renewal characteristics. Tissue or cells can be damaged through a variety of diseases, including hematologic and nonhematologic malignancies. In regard to this, stem-cell transplantation is a cellular therapeutic approach to restore those impaired cells, tissue, or organs. SCs have a therapeutic potential in the application of stem-cell transplantation. Research has been focused mainly on the application of hematopoietic SCs for transplantation. Cord blood cells and human leukocyte antigen–haploidentical donors are considered optional sources of hematopoietic stem–cell transplantation. On the other hand, pluripotent embryonic SCs and induced pluripotent SCs hold promise for advancement of stem-cell transplantation. In addition, nonhematopoietic mesenchymal SCs play their own significant role as a functional bone-marrow niche and in the management of graft-vs-host disease effects during the posttransplantation process. In this review, the role of different types of SCs is presented with regard to their application in SC transplantation. In addition to this, the therapeutic value of autologous and allogeneic hematopoietic stem–cell transplantation is assessed with respect to different types of leukemia. Highly advanced and progressive scientific research has focused on the application of stem-cell transplantation on specific leukemia types. We evaluated and compared the therapeutic potential of SC transplantation with various forms of leukemia. This review aimed to focus on the application of SCs in the treatment of leukemia.

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Enhancement Strategies for Cardiac Regenerative Cell Therapy

Cited by 26 publications

References 98 publications

Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis

Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis

Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

<p>Role of Stem-Cell Transplantation in Leukemia Treatment</p>

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