Abstract

Although mesenchymal stem cells (MSCs) can be obtained from the fetal membrane (FM), little information is available regarding biological differences in MSCs derived from different layers of the FM or their therapeutic potential. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of acute graft-versus-host disease. Our results highlight that human amnion- and chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Highlights

  • Mesenchymal stem cells (MSCs) residing within various tissues, including bone marrow [1] and adipose tissue [2], are reported to differentiate into various types of cells including osteoblasts, chondrocytes, and adipocytes

  • We have previously reported the therapeutic potential of rat fetal membrane (FM)-derived MSCs using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction [3,4,5,6,7,8]

  • Human MSCs derived from bone marrow or adipose tissue exert a regenerative effect in animal models and human patients [14]

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Summary

Introduction

Mesenchymal stem cells (MSCs) residing within various tissues, including bone marrow [1] and adipose tissue [2], are reported to differentiate into various types of cells including osteoblasts, chondrocytes, and adipocytes. This multipotency renders MSCs an attractive therapeutic source for regenerative medicine. Because an invasive procedure is required to obtain autologous bone marrow or adipose tissue-derived MSCs, an alternative source of MSCs that can be obtained non-invasively is desirable. The FM is composed of the amnion and chorion, and both layers contain MSCs [9], it is technically difficult to separate these membranes as well as their MSCs in rat

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