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Cell Stem Cell. 2016 Mar 3;18(3):354-67. doi: 10.1016/j.stem.2015.12.001. Epub 2016 Feb 11.

Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors.

Author information

1
Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, Madison, WI 53705, USA; Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
2
Department of Engineering Physics, University of Wisconsin-Madison, Madison, WI 53705, USA; Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53705, USA; Material Science Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
3
Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.
4
Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, WI 53705, USA.
5
Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
6
Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
7
Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
8
Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Engineering Physics, University of Wisconsin-Madison, Madison, WI 53705, USA; Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53705, USA; Material Science Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
9
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
10
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
11
Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA; Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
12
Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, Madison, WI 53705, USA; Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: tjk@medicine.wisc.edu.

Abstract

Several studies have reported reprogramming of fibroblasts into induced cardiomyocytes; however, reprogramming into proliferative induced cardiac progenitor cells (iCPCs) remains to be accomplished. Here we report that a combination of 11 or 5 cardiac factors along with canonical Wnt and JAK/STAT signaling reprogrammed adult mouse cardiac, lung, and tail tip fibroblasts into iCPCs. The iCPCs were cardiac mesoderm-restricted progenitors that could be expanded extensively while maintaining multipotency to differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells in vitro. Moreover, iCPCs injected into the cardiac crescent of mouse embryos differentiated into cardiomyocytes. iCPCs transplanted into the post-myocardial infarction mouse heart improved survival and differentiated into cardiomyocytes, smooth muscle cells, and endothelial cells. Lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for drug discovery, disease modeling, and cardiac regenerative therapy.

PMID:
26877223
PMCID:
PMC4779406
[Available on 2017-03-03]
DOI:
10.1016/j.stem.2015.12.001
[Indexed for MEDLINE]
Free PMC Article
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