RNA-Mediated Reprogramming of Primary Adult Human Dermal Fibroblasts into c-kit(+) Cardiac Progenitor Cells.

Journal Article

Cardiovascular disease is the leading cause of death in the United States. Heart failure is a common, costly, and potentially fatal condition that is inadequately managed by pharmaceuticals. Cardiac repair therapies are promising alternative options. A potential cardiac repair therapy involves reprogramming human fibroblasts toward an induced cardiac progenitor-like state. We developed a clinically useful and safer reprogramming method by nonintegrative delivery of a cocktail of cardiac transcription factor-encoding mRNAs into autologous human dermal fibroblasts obtained from skin biopsies. Using this method, adult and neonatal dermal fibroblasts were reprogrammed into cardiac progenitor cells (CPCs) that expressed c-kit, Isl-1, and Nkx2.5. Furthermore, these reprogrammed CPCs differentiated into cardiomyocytes (CMs) in vitro as judged by increased expression of cardiac troponin T, α-sarcomeric actinin, RyR2, and SERCA2 and displayed enhanced caffeine-sensitive calcium release. The ability to reprogram patient-derived dermal fibroblasts into c-kit(+) CPCs and differentiate them into functional CMs provides clinicians with a potential new source of CPCs for cardiac repair from a renewable source and an alternative therapy in the treatment of heart failure.

Full Text

Duke Authors

Cited Authors

  • Pratico, ED; Feger, BJ; Watson, MJ; Sullenger, BA; Bowles, DE; Milano, CA; Nair, SK

Published Date

  • November 2015

Published In

Volume / Issue

  • 24 / 22

Start / End Page

  • 2622 - 2633

PubMed ID

  • 26176491

Electronic International Standard Serial Number (EISSN)

  • 1557-8534

International Standard Serial Number (ISSN)

  • 1547-3287

Digital Object Identifier (DOI)

  • 10.1089/scd.2015.0073

Language

  • eng