Stem Cell Therapy for Myocardial Infarction: Challenges and Prospects

Jima, Gizaw Dabessa Satessa

doi:10.4172/2157-7633.1000270

Cited by 7 publications

(6 citation statements)

References 18 publications

(20 reference statements)

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“…Currently available therapies are limited thus far, with a mortality rate of 40% within 5 years post-MI [1]. The success of cell-based therapies in preclinical and clinical trials have been extensively reviewed [2][3][4][5], but these approaches are encountering obstacles to their widespread therapeutic translation due to arrhythmias present in large animal models, cell availability for large-scale manufacturing, and low engraftment levels [6]. Additionally, evidence suggests that the implanted cells primarily serve as a source of paracrine signaling rather than as an engrafted proliferative/differentiative source [7].…”

Section: Introductionmentioning

confidence: 99%

Decellularized neonatal cardiac extracellular matrix prevents widespread ventricular remodeling in adult mammals after myocardial infarction

et al. 2019

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Heart disease remains a leading killer in western society and irreversibly impacts the lives of millions of patients annually. While adult mammals do not possess the ability to regenerate functional cardiac tissue, neonatal mammals are capable of robust cardiomyocyte proliferation and regeneration within a week of birth. Given this change in regenerative function through development, the extracellular matrix (ECM) from adult tissues may not be conducive to promoting cardiac regeneration, although conventional ECM therapies rely exclusively on adultderived tissues. Therefore the potential of ECM derived from neonatal mouse hearts (nmECM) to prevent adverse ventricular remodeling in adults was investigated using an in vivo model of acute myocardial infarction (MI). Following a single administration of nmECM, we observed a significant improvement in heart function while adult heart-derived ECM (amECM) did not improve these parameters. Treatment with nmECM limits scar expansion in the left ventricle and *

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Section: Introductionmentioning

confidence: 99%

Decellularized neonatal cardiac extracellular matrix prevents widespread ventricular remodeling in adult mammals after myocardial infarction

et al. 2019

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“…Among the accepted cell platforms, mesenchymal stem cells (MSCs) are employed in more than 700 registered clinical trials. As an example, MSCs can be used for treatment of graft versus host diseases, cancers, , cardiac damage, − and muscular dystrophy . MSCs have a number of unique functional properties: these cells are adherent and are able to differentiate into osteoblasts, adipocytes, and chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Safe and Effective Delivery of Antitumor Drug Using Mesenchymal Stem Cells Impregnated with Submicron Carriers

Timin

Peltek

Zyuzin

et al. 2019

ACS Appl. Mater. Interfaces

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An important area in modern malignant tumor therapy is the optimization of antitumor drugs pharmacokinetics. The use of some antitumor drugs is limited in clinical practice due to their high toxicity. Therefore, the strategy for optimizing the drug pharmacokinetics focuses on the generation of high local concentrations of these drugs in the tumor area with minimal systemic and tissue-specific toxicity. This can be achieved by encapsulation of highly toxic antitumor drug (vincristine (VCR) that is 20–50 times more toxic than widely used the antitumor drug doxorubicin) into nano- and microcarriers with their further association into therapeutically relevant cells that possess the ability to migrate to sites of tumor. Here, we fundamentally examine the effect of drug carrier size on the behavior of human mesenchymal stem cells (hMSCs), including internalization efficiency, cytotoxicity, cell movement, to optimize the conditions for the development of carrier-hMSCs drug delivery platform. Using the malignant tumors derived from patients, we evaluated the capability of hMSCs associated with VCR-loaded carriers to target tumors using a three-dimensional spheroid model in collagen gel. Compared to free VCR, the developed hMSC-based drug delivery platform showed enhanced antitumor activity regarding those tumors that express CXCL12 (stromal cell-derived factor-1 (SDF-1)) gene, inducing directed migration of hMSCs via CXCL12 (SDF-1)/CXCR4 pathway. These results show that the combination of encapsulated antitumor drugs and hMSCs, which possess the properties of active migration into tumors, is therapeutically beneficial and demonstrated high efficiency and low systematic toxicity, revealing novel strategies for chemotherapy in the future.

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“…Left untreated, these remodeling events lead to cardiac fibrosis and electrophysiological challenge in the myocardium, resulting in heart failure . Recently, significant advances have been made in MI treatment using mesenchymal stem cells (MSCs), with their angiogenic, antiapoptotic, anti-inflammatory, and cardioprotective effects. − Even so, stem cell therapy faces a number of problems including invasive autologous cell isolation procedure, time-consuming and expensive ex vivo cell manipulation, low cell-grafting efficiency, and electrophysiological challenge after implantation. − More recently, implantation of primed dendritic cells (DCs) was utilized to improve wound remodeling and preserve cardiac function after MI via modulating regulatory T cells and macrophages . However, the DC therapy requires time-consuming and costly ex vivo manipulation of DCs and may modulate the whole systemic immune system .…”

mentioning

confidence: 99%

Dual Roles of Graphene Oxide To Attenuate Inflammation and Elicit Timely Polarization of Macrophage Phenotypes for Cardiac Repair

et al. 2018

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Development of localized inflammatory environments by M1 macrophages in the cardiac infarction region exacerbates heart failure after myocardial infarction (MI). Therefore, the regulation of inflammation by M1 macrophages and their timely polarization toward regenerative M2 macrophages suggest an immunotherapy. Particularly, controlling cellular generation of reactive oxygen species (ROS), which cause M1 differentiation, and developing M2 macrophage phenotypes in macrophages propose a therapeutic approach. Previously, stem or dendritic cells were used in MI for their anti-inflammatory and cardioprotective potentials and showed inflammation modulation and M2 macrophage progression for cardiac repair. However, cell-based therapeutics are limited due to invasive cell isolation, time-consuming cell expansion, labor-intensive and costly ex vivo cell manipulation, and low grafting efficiency. Here, we report that graphene oxide (GO) can serve as an antioxidant and attenuate inflammation and inflammatory polarization of macrophages via reduction in intracellular ROS. In addition, GO functions as a carrier for interleukin-4 plasmid DNA (IL-4 pDNA) that propagates M2 macrophages. We synthesized a macrophage-targeting/polarizing GO complex (MGC) and demonstrated that MGC decreased ROS in immune-stimulated macrophages. Furthermore, DNA-functionalized MGC (MGC/IL-4 pDNA) polarized M1 to M2 macrophages and enhanced the secretion of cardiac repair-favorable cytokines. Accordingly, injection of MGC/IL-4 pDNA into mouse MI models attenuated inflammation, elicited early polarization toward M2 macrophages, mitigated fibrosis, and improved heart function. Taken together, the present study highlights a biological application of GO in timely modulation of the immune environment in MI for cardiac repair. Current therapy using off-the-shelf material GO may overcome the shortcomings of cell therapies for MI.

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Stem Cell Therapy for Myocardial Infarction: Challenges and Prospects

Cited by 7 publications

References 18 publications

Decellularized neonatal cardiac extracellular matrix prevents widespread ventricular remodeling in adult mammals after myocardial infarction

Decellularized neonatal cardiac extracellular matrix prevents widespread ventricular remodeling in adult mammals after myocardial infarction

Safe and Effective Delivery of Antitumor Drug Using Mesenchymal Stem Cells Impregnated with Submicron Carriers

Dual Roles of Graphene Oxide To Attenuate Inflammation and Elicit Timely Polarization of Macrophage Phenotypes for Cardiac Repair

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