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Brain & Heart Mesenchymal cell therapy for heart disease

that use this cutting-edge regeneration methodology. The stimulation of cardiac stem cells, and decreased myocardial
simple isolation, expansion, and versatile in vitro multi- fibrosis. Nakanishi et al. found that the expression of two
19
lineage potential of MSCs make them attractive therapeutic cardiac progenitor genes, myosin heavy chain and atrial
candidates in the field of regenerative medicine. natriuretic peptide, was upregulated in the conditioned
medium of MSCs. The migration and differentiation of
2. Mechanisms of MSC therapy in cardiac cardiac progenitor cells were promoted by the paracrine
disease effect of soluble substances. 20
MSCs were first discovered from BM by Friedenstein Exosomes and EVs are the membrane-restricted
and his colleagues in 1976. The BM, adipose tissue, and biological components employed in regenerative
4
umbilical cord-derived MSCs have diverse capacities medicine. The expression of CD13, CD29, CD44, CD73,
for immunoregulation and differentiation in CVDs. and CD105 in the secretome of EV from MSC diminishes
The properties of MSCs, including their activity and the characteristics of the MSCs’ origins. 21,22 Moreover,
immunoregulatory potential, can be influenced by the coding mRNA of EVs contains transcription
variations in culture conditions. The International Society factors that control transcription, cell division, and
5
for Cellular Therapy has established criteria for MSCs, immunomodulation. Within the non-coding RNAs that
23
including being plastic adherent, expressing specific prevent the release of EV-MSCs, they exhibit a distinct
21
positive CD markers, and differentiating to adipocytes, pattern. This mRNA successfully prevents apoptosis
chondrocytes, and osteocytes. When cultivated in the in ischemic cardiomyocytes by downregulating the
laboratory, MSCs exhibit three key biological traits that production of the Bcl-2 protein family subset, the p53-
make them suitable for cell therapy: (i) The ability to stimulated modulator of apoptosis. Exosomes and MSCs
24
differentiate; (ii) the secretion of trophic factors that support were delivered with intramyocardial injection into acute
tissue remodeling; and (iii) immunoregulatory properties. MI to improve the milieu, minimize the inflammatory
MSC’s exact mechanism of action on cardiac repair is still response, and improve cardiac function. Host cells act
25
unclear. However, there are specific, feasible mechanisms: as mediators for various immunomodulatory actions
6
(i) The ability to graft new cells and differentiate mediated by MSCs. After cardiac injury, the regeneration
them into distinct cell types, such as cardiomyocytes; process is regulated by the clearance of cell debris,
7
(ii) adverse effects on cardiac repair through paracrine stimulation of local precursor cells, and regrowth of cardiac
signaling/mediators of MSCs; (iii) stimulation of native tissue to compensate for qualitative and quantitative
8
cardiac stem cells (CSC) to promote tissue growth and changes in the vascular network, fibrotic scar formation,
26
9
repair; and (iv) promotion of neovascularization and and inflammatory responses. Anti-inflammatory M1
immunomodulation. 10 macrophages, soluble mediators such as prostaglandin E2,
hepatocyte growth factor, indoleamine 2,3-dioxygenase,
The numerous methods of in vivo transfer of MSC soluble HLA G5, heme oxygenase-1, transforming growth
to improve the cardiac efficiency of some vital routes of factor-1, and anti-inflammatory interleukin 10 (IL10)
administration are (i) transendocardial stem cell injection are well-known components in this process. In the
27
(TESI), 11,12 (ii) peripheral intravenous infusion, 13,14 adaptive system, MSCs block the maturation of B cells
(iii) catheter-based direct intramyocardial delivery, and and dendritic cells, dampen the proliferation of T helper
15
(iv) intracoronary infusion delivery. 16,17 Transendocardial (Th) cells and cytotoxic T cells, and stop the production of
injection of 20 – 100 × 10 MSCs yielded the most favorable proinflammatory cytokines by T-cells. They also decrease
6
outcomes compared to other methods in cardiovascular the activating receptors of the natural killer cells in the
clinical trials. 18 innate system. This reduces the inflammatory response
3. Paracrine effect, extracellular in mice’s hearts following the start of MI the intravenous
vesicles (EVs) and exosomes, and secretion of a protein induced by TNF-stimulated gene-6
(TSG-6).
It has been shown that modifying MSCs
28,29
immunomodulatory effects of MSCs in with different growth factors and cytokines improves
heart disease vascularization and cardiac remodeling, decreases
A comparison of the paracrine effect, EVs, and exosomes inflammation, and increases angiogenesis. 28
of MSCs is summarized in Figure 1. In addition to the cell- 4. MSCs in animal models for the treatment
mediated immunologic response, paracrine substances of MI
secreted by the body have a range of beneficial effects in
the myocardium, such as enhanced local angiogenesis, A list of clinical trials using animal models on mesenchymal-
reduced cardiomyocyte mortality, low fibroblast activation, based stem cell therapy is presented in Table 1. In vivo tests

Volume 2 Issue 1 (2024) 2 https://doi.org/10.36922/bh.2065