STEM CELL THERAPY FOR CARDIOVASCULAR DISEASES

Stem cell-based therapies for vascular regeneration in patients with cardiovascular ischemic diseases initially relied on a very simple concept: therapeutic stem/progenitor cells might differentiate into vascular cells, mainly of endothelial phenotype, increasing new vessel formation and tissue perfusion in the ischemic milieu. This exciting notion challenged the scientific community to start the quest for the Holy Grail in vascular regenerative medicine: the search for the ideal source of endothelial stem/progenitor cells. This concept leads to the development of salutary approaches based on the use of therapeutic autologous adult stem cells thought to contain such bona-fide endothelial progenitor cells such as bone marrow- or peripheral blood-derived mononuclear cells. Beside the classical technical caveats including modalities of cell transfer and optimization of cell engraftment, the negative impact of cardiovascular risk factors as well as the low rate of incorporation of adult stem cells in the targeted vasculature likely explain the mixed results obtained in numerous phase I-II clinical trials incorporating patients with peripheral artery or cardiac diseases. Hence, alternative sources of stem cells have been considered to leverage their intrinsic pluripotentiality and drive them towards a vascular lineage. Both embryonic stem cells and induced pluripotent stem cells have then been tested in various experimental models of post-ischemic vascularization. However, as for their adult counterpart, these “embryonic” cells do not structurally integrate within the recipient vascular network but likely release biomolecules that fine-tune endogenous repair processes. A precise characterization of the cell-released factors purportedly accounting for their benefits still remains elusive. However, there are mounting evidences to suggest that stem cells can release extracellular membrane vesicles that may contain vascular regenerative entities. Hence, the natural evolution of the stem cell theory for vascular regeneration may end with the development of cell-free strategies with multiple cellular targets including vascular cells but also other infiltrating or resident cells.

Abstract licence: CC BY

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