Strategies for Cardiovascular Regeneration via Cell Therapies

Researchers here review one slice of the cell therapy field, examining the use of mesenchymal stem cells to provoke greater regeneration of heart tissue than normally takes place. While stem cell therapies are generally at least marginally beneficial, with reduction in inflammation the most reliable outcome to date, the research community has so far struggled to consistently produce larger benefits when it comes to heart damage in older people.

The treatment approach for the majority of cardiovascular disease is to administer drugs, and some cases may require surgery such as coronary angioplasty with stent insertion. The incidence of cardiovascular disease has continued to increase, and aside from transplantation, other therapies, despite recent advances in heart treatments, cannot fundamentally remedy the major etiology of cardiovascular disease; thus, there is a limit to how much treatment outcomes can be improved with the current approaches. Although various studies have been conducted ​​to overcome the limitations of cardiovascular therapies, stem cell therapy using several types of stem cells such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), cardiac stem cells (CSCs), and endothelial progenitor cells (EPCs) provides an alternative approach, and ​​remarkable advances have been made in clinical and basic research.

Among adult stem cells, MSCs are frequently used to treat the most common cardiovascular diseases. MSCs can be found in the bone marrow (BM), adipose tissue, umbilical cord blood (UCB), and many other tissues. They have self-renewing properties and are multipotent progenitor cells that can differentiate into various lineages such as osteocytes, chondrocytes, adipocytes, and myocytes. MSCs also have immunomodulatory properties, and in addition MSCs are unlikely to lead to immune rejection. The therapeutic benefit of this approach is based on the potency of secretion of beneficial cytokines and growth factors for tissue repair/regeneration, as well as the immunomodulation effect and/or their differentiation for regenerating damaged organs.

MSCs can be applied for cardiovascular regeneration and provide therapeutic benefit for cardiovascular disease. However, MSCs have several disadvantages regarding their therapeutic application, including their very low survival rate in vivo and integration rate into the host cells after transplantation. Another limitation is the low accuracy in delivering the stem cells to the damaged site. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. The first step in developing therapeutic strategies is the identification of more effective reagents for promoting the ability of stem cells via understanding stem cell niche modulators. An emerging promising therapeutic strategy is the preconditioning of MSCs before transplantation using cytokines and natural compounds that induce intracellular signaling or niche stimulation through paracrine mechanisms. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as extracellular matrix or hydrogel, and cell patch- and 3D printing-based tissue engineering, to enhance cell survival via cell-cell communication or cell-scaffold interactions. Because of its numerous applications, a combined therapeutic strategy that includes cell priming and tissue engineering technology is a promising therapeutic approach for cardiovascular regeneration.



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