Stem Cell Therapy, Artificial Heart or Xenotransplantation: What will be New "Regenerative" Strategies in Heart Failure during the Next Decade?

Stem Cell Rev Rep. 2022 Nov 16. doi: 10.1007/s12015-022-10476-z. Online ahead of print.

Abstract

The main limitation of allotransplantation and in particular heart transplantation is the insufficient supply of donor organs. As alternative strategies to heart transplantation, stem cells opened the way of regenerative medicine in early 2000. While new biotechnologies tried to minimize side effects due to hemocompatibility in artificial hearts, progress in xenotransplantation allowed in 2022 to realize the first pig-to-human heart transplant on a compassionate use basis. This xenotransplantation has been successful thanks to genetically modified pigs using the CRISPR-Cas9 technology. Indeed, gene editing allowed modifications of immune responses and thrombotic potential to modulate graft and systemic reaction. Academic research and preclinical studies of xenogeneic tissues already used in clinic such as bioprosthesis valve and of new xenotransplantation options will be necessary to evaluate immune-thrombosis and organ/vascular damages more deeply to make this hope of xenotransplantation a clinical reality. Stem cells, artificial heart and xenotransplantation are all in line to overcome the lack of donor hearts. Combination of stem cell approaches and/or xenogeneic tissue and/or artificial organs are probably part of the research objectives to make these projects real in the short term.

Keywords: Artificial heart; EPCR; Heart failure; Stem cells; Thrombomodulin; VSELs; Xenotransplantation.