Abstract

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that is isolated initially from the bone marrow (BM) and subsequently almost all tissues including umbilical cord (UC). UC-derived MSCs (UC-MSCs) have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA). These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation.

Highlights

  • Mesenchymal stem cells (MSCs) are a heterogeneous cell population that has a potential to proliferate and differentiate into trilineage mesenchymal cells: adipocytes, osteocytes, and chondrocytes

  • We isolated umbilical cord (UC)-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation

  • UC-derived MSCs (UC-MSCs) Isolated from Infants Delivered at 22–40 Weeks of Gestation

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Summary

Introduction

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that has a potential to proliferate and differentiate into trilineage mesenchymal cells: adipocytes, osteocytes, and chondrocytes. MSCs were initially isolated and characterized from the bone marrow (BM) [1, 2] and subsequently derived from almost all tissues including adipose tissue (AT), synovium, skin, dental pulp, umbilical cord blood (UCB), placenta, and umbilical cord (UC) [3]. Due to the ability to home to sites of injury, undergo differentiation, suppress immune responses, and modulate angiogenesis, MSCs are paid an increasing attention as a source for cell therapy against various degenerative diseases. BM is the most well-characterized source of MSCs, it has certain limitations with the invasive BM aspiration and the decline in MSC proliferation and differentiation capacity with age. Fetal MSCs obtained from UCB, placenta, and UC have advantages with the noninvasive sampling during newborn delivery and the vigorous proliferation and differentiation capacity for cell therapy [6, 7]. UC-derived MSCs (UC-MSCs) will become a promising source for cell therapy [8, 9]

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