Mesenchymal Stem Cell Transplantation for Ischemic Diseases: Mechanisms and Challenges

Abstract

Ischemic diseases are conditions associated with the restriction or blockage of blood supply to specific tissues. These conditions can cause moderate to severe complications in patients, and can lead to permanent disabilities. Since they are blood vessel-related diseases, ischemic diseases are usually treated with endothelial cells or endothelial progenitor cells that can regenerate new blood vessels. However, in recent years, mesenchymal stem cells (MSCs) have shown potent bioeffects on angiogenesis, thus playing a role in blood regeneration. Indeed, MSCs can trigger angiogenesis at ischemic sites by several mechanisms related to their trans-differentiation potential. These mechanisms include inhibition of apoptosis, stimulation of angiogenesis via angiogenic growth factors, and regulation of immune responses, as well as regulation of scarring to suppress blood vessel regeneration when needed. However, preclinical and clinical trials of MSC transplantation in ischemic diseases have shown some limitations in terms of treatment efficacy. Such studies have emphasized the current challenges of MSC-based therapies. Treatment efficacy could be enhanced if the limitations were better understood and potentially resolved. This review will summarize some of the strategies by which MSCs have been utilized for ischemic disease treatment, and will highlight some challenges of those applications as well as suggesting some strategies to improve treatment efficacy.

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Fig. 1
Fig. 2

modified by the presence of MSC administration (blue arrow). Changes in the environment such as oxygen and nutrition deprivation and host immune response can negatively affect the survival and proliferation of MSCs. On the other hand, the administration of MSCs during ischemic condition can help to reverse the damages caused by ischemic condition. Improvement of the condition is induced by the effect generated from MSCs characteristics of immunomodulation, microenvironment generation, homing and differentiation. MSCs generate secretome containing growth factors, cytokines and chemokines to modulate the host immune response, resolving cell death signal and balancing angiogenic and angiostatic pool in the ischemic site. MSCs can also home and guide the regeneration of nerve in the ischemic tissue to support tissue recovery

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Acknowledgements

All authors equally contributed in this work. All authors read and approved the final manuscript.

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Correspondence to Phuc Van Pham.

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Van Nguyen, TT., Vu, N.B. & Van Pham, P. Mesenchymal Stem Cell Transplantation for Ischemic Diseases: Mechanisms and Challenges. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00334-3

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Keywords

  • Ischemic diseases
  • Mesenchymal stem cells
  • Blood regeneration and angiogenesis