Therapeutic Applications of Engineered Mesenchymal Stromal Cells for Enhanced Angiogenesis in Cardiac and Cerebral Ischemia

Stem Cell Rev Rep. 2024 Nov;20(8):2138-2154. doi: 10.1007/s12015-024-10787-3. Epub 2024 Sep 21.

Abstract

Ischemic diseases are characterized by obstruction of blood flow to the respective organs, of which ischemia of the heart and brain are the most prominent manifestations with shared pathophysiological mechanisms and risk factors. While most revascularization therapies aim to restore blood flow, this can be challenging due to the limited therapeutic window available for treatment approaches. For a very long time, mesenchymal stromal cells have been used to treat cerebral and cardiac ischemia. However, their application is restricted either by inefficient mode of delivery or the low cell survival rates following implantation into the ischemic microenvironment. Nonetheless, several studies are currently focusing on using of mesenchymal stromal cells engineered to overexpress therapeutic genes as a cell-based gene therapy to restore angiogenesis. This review delves into the utilization of MSCs for angiogenesis and the applications of engineered MSCs for the treatment of cardiac and cerebral ischemia. Moreover, the safety issues related to the genetic modification of MSCs have also been discussed.

Keywords: Angiogenesis; Gene modification; Ischemia; Mesenchymal stromal cells; Secretome.

Publication types

  • Review

MeSH terms

  • Angiogenesis
  • Animals
  • Brain Ischemia* / pathology
  • Brain Ischemia* / therapy
  • Genetic Therapy
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Myocardial Ischemia* / pathology
  • Myocardial Ischemia* / therapy
  • Neovascularization, Physiologic*