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Brain & Heart                                                     Mesenchymal cell therapy for heart disease




























            Figure 1. Comparison of therapeutic effects of mesenchymal derived exosomes, extracellular vesicles, and their paracrine effects.
            Table 1. Summary of clinical trials in animal models

            Animal model  Cell source  Condition  Method         Outcome                             References
            Rat         Adipose       AMI      Transplantation   Acceleration of angiogenesis in the infarcted area after   47
                        tissue-derived                           rat myocardial infarction and improvement of heart
                        MSC                                      function
            Rat         Human umbilical   DCM  Intravenous injection  Improved cardiac function through induction of   32
                        cord MSC                                 myogenesis and angiogenesis; also inhibits myocardial
                                                                 fibrosis
            Pig         Allogenic BM MSC  AMI  Intramyocardial injection Successful in intramyocardial engraftment and   48
                                                                 differentiation into a cardiomyocyte
            Swine       BM            AMI      Intracoronary infusion  Regenerated new myocardium and prevent remolding   35
                        magnetic-labeled                         at 2-month follow-up
                        MSC
            Swine       Allogenic adipose   AMI  Intracoronary infusion  Increased cardioprotective and reparative mechanisms   49
                        tissue-derived                           and better cardiac magnetic resonance-measured
                        MSC                                      perfusion
            Abbreviations: AMI: Acute myocardial infarction; BM: Bone marrow; DCM: Dilated cardiomyopathy; MSC: Mesenchymal stem cell.

            on animal models of the specific disease are still required   studies found that 5  days after MI, an intracoronary
            before those findings can be applied to humans. Due to   injection of MSC cells into the pig heart increased LVEF
            their small size, ease of handling, low maintenance, and   and reduced infarct scar size.  Four weeks after MI, lambs
                                                                                      35
            low cost, small animals such as mice, rats, and rabbits   were  given allogeneic  mesenchymal precursor cells and
            are commonly employed as models for studying CVDs.   demonstrated neovascularization. 34
            Orlic et al. experimented on female mice with acute MI
            (AMI), promoting cardiac regeneration.  Transplantation   5. Clinical trials with MSC
                                            30
            of BM-derived MSCs stimulated with 5-azacytidine led to
            differentiation into cells resembling cardiomyocytes and   The initial clinical trial was conceived as a randomized
            cardiac cells in the rabbit model of dilated cardiomyopathy   study. In the prospective memory training to improve heart
            (DCM).  Human umbilical cord-MSCs were used to treat   failure self-care (PROMETHUS) trial, autologous BM was
                  31
            the DCM rat model, which reduced fibrosis.  However,   injected into kinetic myocardial regions intramyocardially.
                                                 32
            small changes in  in vivo animal models have certain   In comparison to patients who received a placebo
            disadvantages. Therefore, animals such as pigs, porcupines,   control, MSC-treated patients showed a lower scar mass
            dogs, and sheep are used in scientific investigations.  Pigs’   (−47.5 ± 8.1%, P < 0.0001) and a greater LVEF (+9.4 ± 1.7%,
                                                     33
            left ventricular ejection fraction (LVEF) is improved by   P = 0.0002). In addition, they noted logical restrictions on
            intravenous injection of BM-derived MSCs.  Different   scar contractility, perfusion, and size.  The safety of two
                                                                                             36
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            Volume 2 Issue 1 (2024)                         3                         https://doi.org/10.36922/bh.2065
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