N-cadherin Determines Individual Variations in the Therapeutic Efficacy of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells in a Rat Model of Myocardial Infarction

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2011 Nov 10

PMID 22068423

Citations 28

Authors

Eun Ju Lee

Eue-Keun Choi

Soo Kyoung Kang

Gi-Hwan Kim

Ju Young Park

Hyun-Jae Kang

Sae-Won Lee

Keum-Hyun Kim

Jin Sook Kwon

Ki Hong Lee

Youngkeun Ahn

Ho-Jae Lee

Hyun-Jai Cho

Soo Jin Choi

Won Il Oh

Young-Bae Park

Hyo-Soo Kim

Affiliations

Soon will be listed here.

Abstract

In this study, we established and characterized human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from four different donors. However, the hUCB-MSCs showed remarkable variations in their therapeutic efficacy for repairing rat infarcted myocardium (including the process of angiogenesis) 8 weeks after transplantation. In addition, we observed that the level of vascular endothelial growth factor (VEGF) is correlated with the therapeutic efficacy of the four hUCB-MSCs. Next, to investigate the practical application of hUCB-MSCs, we searched for surface signature molecules that could serve as indicators of therapeutic efficacy. The gene for N-cadherin was the only cell surface gene that was highly expressed in the most effective hUCB-MSCs, both at the transcriptional and translational levels. We observed downregulation and upregulation of VEGF in response to N-cadherin blocking and N-cadherin overexpression, respectively. Activation of extracellular signal-regulated kinase (ERK), but not protein kinase B, was increased when N-cadherin expression was increased, whereas disruption of N-cadherin-mediated cell-cell contact induced suppression of ERK activation and led to VEGF downregulation. Moreover, by investigating hUCB-MSCs overexpressing N-cadherin or N-cadherin knockdown hUCB-MSCs, we confirmed the in vivo function of N-cadherin. In addition, we observed that DiI-labeled hUCB-MSCs express N-cadherin in the peri-infarct area and interact with cardiomyocytes.

Citing Articles

N-CADHERIN/CD168 subpopulation determines therapeutic variations of UC-MSCs for cardiac repair after myocardial infarction.

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A division-of-labor mode contributes to the cardioprotective potential of mesenchymal stem/stromal cells in heart failure post myocardial infarction.

Wang X, Yang C, Ma X, Li X, Qi Y, Bai Z Front Immunol. 2024; 15:1363517.

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Effect of Expansion Media on Functional Characteristics of Bone Marrow-Derived Mesenchymal Stromal Cells.

Jakl V, Popp T, Haupt J, Port M, Roesler R, Wiese S Cells. 2023; 12(16).

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