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Brain & Heart                                                          Stem cells in cardiovascular disease








































            Figure 2. Improving the targeted transplantation of stem cells through in vitro differentiation: improving survival rates and adaptation within 3D cardiac
            environments in tissue engineering and the significant role of exosome utilization. Image created by the authors.
            clinical safety. Genomic instability during reprogramming   factors can affect cell development, the laboratory provides
            raises concerns, making ESCs the preferred choice for now   controlled environments to guide differentiation. All
            until more stable reprogramming methods are developed.    pluripotent cells, including VSELs, can be predifferentiated
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            MSCs are widely used in cardiac research due to their   to align with specific therapeutic goals, thereby improving
            potential. Optimizing the isolation and expansion of   their engraftment and therapeutic potential. 23,24,27  For
            VSELs is also important, because banking hUCB-VSELs   instance, Szaraz et al.  found that human umbilical cord
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            could create a valuable cell reservoir for treating congenital   perivascular cells formed contracting clusters within
            or acquired heart diseases.                        a week when cocultured on cardiac feeder layers, thus

              Major challenges for transplanted stem cells include   addressing low survival rates post-transplantation due
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            minimizing apoptosis, oxidative stress, and inflammation   to leakage, ischemic conditions, or oxidative stress.
            that can result in cell death and cardiac complications.   Furthermore, exosomes from failing hearts exhibit
            Efforts must focus on improving cell survival, angiogenesis,   diminished cardioprotective properties compared with
            and cardiac function to support the damaged myocardium.   those from healthy hearts, emphasizing the need for ex vivo
            It is also important for transplanted cells to survive,   improvements to stem cell function. 22
            integrate properly, and receive appropriate electrical and   The stem cell secretome is pivotal in therapies,
            mechanical signals to develop into functional heart cells.   comprising proteins, nucleic acids, lipids, and extracellular
            There are also challenges related to exosomes, such as   vesicles  (EVs). EVs, categorized by size and origin,
            specificity, dosing, and target binding.           include exosomes, mRNAs, microRNAs, and non-
              A major challenge with undifferentiated stem cells   coding RNAs, all of which are essential for intercellular
            is  their  tendency  to  differentiate  into  various  cell  types   communication. 24,28  Exosomes, involved in processes such
            in vivo, resulting in poor cardiomyogenic outcomes.   as  immune  modulation  and  differentiation,  demonstrate
            Predifferentiating them toward a cardiomyogenic lineage   potential for cardiac regeneration. For instance, Farahzadi
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            in vitro  significantly improves their efficacy. Unlike   et al.  demonstrated that injecting MSC-derived exosomes
            in vivo conditions, where oxidative stress and unpredictable   into mice shortly before cardiac reperfusion significantly

            Volume 2 Issue 4 (2024)                         7                                doi: 10.36922/bh.4521
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