Bone-derived stem cells repair the heart after myocardial infarction through transdifferentiation and paracrine signaling mechanisms
Authors: Steven R Houser
Thomas E Sharp
Hajime Kubo
Yumi Chiba
Nicholas E Hoffman
Timothy Starosta
Jason M Duran
Remus M Berretta
Muniswamy Madesh
Fang Zhu
Catherine A Makarewich
Journal: Circulation Research (2013)
Discipline: CLINICAL MEDICINE
Keywords: differentiation; myocardial infarction; neovascularization; paracrine communication; stem cells.
Affiliations: Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA., From the Cardiovascular Research Center (J.M.D., C.A.M., T.E.S., T.S., Y.C., R.M.B., H.K., S.R.H.) and Medicine Center for Translational Medicine (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; and Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, PA (F.Z.).

Abstract:  Rationale: Autologous bone marrow-derived or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials, but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is the key toward improving clinical outcomes. Objective: To determine the mechanism by which novel bone-derived stem cells support the injured heart. Methods and results: Cortical bone-derived stem cells (CBSCs) and cardiac-derived stem cells were isolated from enhanced green fluorescent protein (EGFP+) transgenic mice and were shown to express c-kit and Sca-1 as well as 8 paracrine factors involved in cardioprotection, angiogenesis, and stem cell function. Wild-type C57BL/6 mice underwent sham operation (n=21) or myocardial infarction with injection of CBSCs (n=67), cardiac-derived stem cells (n=36), or saline (n=60). Cardiac function was monitored using echocardiography. Only 2/8 paracrine factors were detected in EGFP+ CBSCs in vivo (basic fibroblast growth factor and vascular endothelial growth factor), and this expression was associated with increased neovascularization of the infarct border zone. CBSC therapy improved survival, cardiac function, regional strain, attenuated remodeling, and decreased infarct size relative to cardiac-derived stem cells- or saline-treated myocardial infarction controls. By 6 weeks, EGFP+ cardiomyocytes, vascular smooth muscle, and endothelial cells could be identified in CBSC-treated, but not in cardiac-derived stem cells-treated, animals. EGFP+ CBSC-derived isolated myocytes were smaller and more frequently mononucleated, but were functionally indistinguishable from EGFP- myocytes. Conclusions: CBSCs improve survival, cardiac function, and attenuate remodeling through the following 2 mechanisms: (1) secretion of proangiogenic factors that stimulate endogenous neovascularization, and (2) differentiation into functional adult myocytes and vascular cells. 

Retracted: No

PubPeer comments:
 Figure 1A appears to have a repeated image. *** ![file] , 
 Strangely, the current version of the paper has a slightly different version of this figure where the HGF panel has been replaced by another panel. Yet, the paper does not have an official correction. Could the authors please comment? , 
 #2 Published January 7, 2021 u201cIn the article by Duran et al entitled u201cBone-Derived Stem Cells Repair the Heart After Myocardial Infarction Through Transdifferentiation and Paracrine Signaling Mechanisms,u201d which published online on June 25, 2013 and appeared in print in the August 16, 2013 issue of the journal (Circ Res. 2013;113:539-552. doi: 10.1161 CIRCRESAHA.113.301202), a correction was needed. An error was discovered in Figure 1A. While generating this figure panel, the authors accidentally duplicated the angiopoietin-1 (Ang-1) Western blot and displayed this data for both Ang-1 and hepatocyte growth factor (HGF). The original film intended to be used for the HGF Western blot for Figure 1A has now been provided to the journal for correction of this mistake. This correction does not alter the interpretation of the Figure nor that of the article. The authors apologize for this error. The corrected version of this article is available at https: www.ahajournals.org doi full 10.1161 CIRCRESAHA.113.301202u201d As the authors did not care to reply here, we do not know if the uncropped gel image was supplied to the journal or merely a replacement figure without the duplication. ,