Tissue-specific Differentiation Potency of Mesenchymal Stromal Cells from Perinatal Tissues.

Ahlm Kwon,Myungshin Kim,Jung Min Kim,Dong Wook Jekarl,Hayoung Choi,Yonggoo Kim,Seungok Lee,Jong-Chul Shin,In Yang Park,Jiyeon Kim

doi:10.1038/srep23544

Abstract

Human perinatal tissue is an abundant source of mesenchymal stromal cells(MSCs) and lacks the ethical concerns. Perinatal MSCs can be obtained from various tissues as like amnion, chorion, and umbilical cord. Still, little is known of the distinct nature of each MSC type. In this study, we successfully isolated and cultured MSCs from amnion(AMSCs), chorion(CMSCs), and umbilical cord(UC-MSCs). Proliferation potential was different among them, that AMSCs revealed the lowest proliferation rate due to increased Annexin V and senescence-associated β-galactosidase positive cells. We demonstrated distinct characteristic gene expression according to the source of the original tissue using microarray. In particular, genes associated with apoptosis and senescence including CDKN2A were up-regulated in AMSCs. In CMSCs, genes associated with heart morphogenesis and blood circulation including HTR2B were up-regulated. Genes associated with neurological system processes including NPY were up-regulated in UC-MSCs. Quantitative RT-PCR confirmed the gene expression data. And in vitro differentiation of MSCs demonstrated that CMSCs and UC-MSCs had a more pronounced ability to differentiate into cardiomyocyte and neural cells, respectively. This study firstly demonstrated the innate tissue-specific differentiation potency of perinatal MSCs which can be helpful in choosing more adequate cell sources for better outcome in a specific disease.

Highlights

Mesenchymal stromal cells (MSCs) have the potential for self-renewal, immunomodulation, and differentiation into mesoderm lineages in vitro and in vivo
population doubling time (PDT) values of amnion-derived MSCs (AMSCs), chorionic MSCs (CMSCs), and umbilical cord-derived MSCs (UC-MSCs) increased during the processing of passages (Fig. 1B)
According to gene expression data, we evaluated the potentials of CMSCs and UC-MSCs to differentiate into cardiomyocytes and neural cells, Figure 1. (A) Morphology of amnionic mesenchymal stromal cells(AMSCs) at primary culture, passage 3 and 6, chorionic MSCs (CMSCs), and umbilical cord MSCs (UC-MSCs) in primary culture, passage 3 and 10 (x40). (B) Comparison of population doubling time among AMSCs, CMSCs and UC-MSCs. (C) Evaluation of apoptosis by Annexin V-fluorescein isothiocynate (FITC)/propidium iodide (PI) staining, followed by flow cytometry analysis. (D) Evaluation of Senescence by β -galactosidase activity assay. (E) Mesodermal differentiation potential of mesenchymal stromal cells derived from amnion (AMSCs), chorion (CMSCs) and umbilical cord (UC-MSCs)

Summary

Introduction

Mesenchymal stromal cells (MSCs) have the potential for self-renewal, immunomodulation, and differentiation into mesoderm lineages in vitro and in vivo. This study had four purposes: 1) to isolate and characterize AMSCs, CMSCs, and UC-MSCs from different human term perinatal tissues; 2) to compare differences in cellular proliferation, immunophenotype, and mesodermal differentiation potential; 3) to examine their gene expression profiles and investigate their differences; and 4) to determine the differentiation potential of each MSC-type. To confirm that isolated and cultured cells from three perinatal tissues corresponded to MSCs10, we tested the expression of several MSC phenotypical markers including CD105, CD90, and CD73.

Results

Conclusion