Combining cell and gene therapy to advance cardiac regeneration

Expert Opin Biol Ther. 2018 Apr;18(4):409-423. doi: 10.1080/14712598.2018.1430762. Epub 2018 Jan 24.

Abstract

Introduction: The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration.

Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial. The in vivo test of somatic reprogramming and cardioregenerative non-coding RNAs revived the interest in gene therapy for myocardial regeneration. The latter, together with the advent of genome editing, has prompted most recent efforts to produce genetically-modified allogeneic CSCs that secrete cardioregenerative factors to optimize effective myocardial repair.

Expert opinion: The current war against heart failure epidemics in western countries seeks to find effective treatments to set back the failing hearts prolonging human lifespan. Off-the-shelf allogeneic-genetically-modified CSCs producing regenerative agents are a novel and evolving therapy set to be affordable, safe, effective and available at all times for myocardial regeneration to either prevent or treat heart failure.

Keywords: Cardiac regeneration; cardiac stem cells; genome editing; non-coding RNAs; somatic reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy*
  • Cellular Reprogramming
  • Gene Editing*
  • Heart / physiology*
  • Humans
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Regeneration
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • RNA, Untranslated