Human Umbilical Cord-Derived Mesenchymal Stem Cells Spontaneously Form 3D Aggregates and Differentiate in an Embryoid Body-Like Manner

Abstract

Human adult mesenchymal stem cells (hMSC) are particularly suitable cells for autologous tissue engineering and cell-based therapies. They can be isolated from various tissues, such as bone marrow, adipose tissue, dental pulp or umbilical cords. Due to their primitive developmental stage, umbilical cord-derived hMSC are assumed to have a higher proliferation and differentiation capacity than hMSC from adult tissues. We isolated hMSC from bone marrow (BM) and umbilical cords (UC) and compared the cells regarding their surface epitopes, proliferation and differentiation capacity. Flow cytometry of specific surface epitopes showed that both BM-MSC and UC-MSC display the characteristic MSC phenotype. Cells from both sources were readily differentiated into adipocytes, osteoblasts and chondrocytes according to standard protocols. Interestingly, only UC-MSC spontaneously formed three-dimensional aggregates when cultured under post-confluent conditions. The cells of these aggregates were viable and spontaneously differentiated into several specialized cell types akin to the well-known differentiation of embryoid bodies. Besides, UC-MSC expressed the pluripotency-associated gene NANOG as well as genes characteristic for the mesodermal and ectodermal fate. Thus, UC-MSC resemble BM-MSC but additionally show a spontaneous embryoid body-like aggregation and differentiation in vitro. These results indicate that UC-MSC are less restricted than BM-MSC and may thus extend the limits of BM-MSC based therapies.