Homogeneity and heterogeneity of biological characteristics in mesenchymal stem cells from human umbilical cords and exfoliated deciduous teeth.

Mesenchymal stem cells (MSCs) have proven powerful potential for cell-based therapy both in regenerative medicine and disease treatment. Human umbilical cords and exfoliated deciduous teeth are the main sources of MSCs with no donor injury or ethical issues. The goal of this study was to investigate the differences in the biological characteristics of human umbilical cord mesenchymal stem cells (UCMSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). UCMSCs and SHEDs were identified by flow cytometry. The proliferation, differentiation, migration, chemotaxis, paracrine, immunomodulatory, neurite growth-promoting capabilities, and acetaldehyde dehydrogenase (ALDH) activity were comparatively studied between these two MSCs in vitro. The results showed that both SHEDs and UCMSCs expressed cell surface markers characteristic of MSCs. Furthermore, SHEDs exhibited better capacity for proliferation, migration, promotion of neurite growth, and chondrogenic differentiation. Meanwhile, UCMSCs showed more outstanding adipogenic differentiation and chemotaxy. Additionally, there were no significant differences in osteogenic differentiation, immunomodulatory capacity, and the proportion of ALDHBright compartment. Our findings indicate that although both UCMSCs and SHEDs are mesenchymal stem cells and presented some similar biological characteristics, they also have differences in many aspects, which might be helpful for developing future clinical cellular therapies.

The biological changes of umbilical cord mesenchymal stem cells in inflammatory environment induced by different cytokines.

Mesenchymal stem cells (MSCs) are used as therapeutic tool for the treatment of immune diseases. The inflammatory environment also influences the characteristics of MSCs after transplantation. The aim of the study was to investigate the effects of pro-inflammatory cytokines on the characteristics of umbilical cord mesenchymal stem cells (UCMSCs). UCMSCs were exposed to pro-inflammatory cytokines in vitro for 3 and 7 days, and the biological properties were analyzed. The results showed that the proliferation ability was suppressed by interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). The adipogenic capacity was inhibited in all conditioned medium, while the chondrogenic and osteogenic capacity was enhanced by TNF-α and IL-1ß in vitro. Prostaglandin E2 (PGE2) was increased by IL-1ß on the third day, and angiopoietin-1 (Ang-1) was inhibited appreciably by TNF-α on the seventh day. Interleukin-6 (IL-6) was increased by TNF-α and IL-1ß, and hepatocyte growth factor (HGF) was inhibited by all inflammatory cytokines. IFN-γ secretion level from human peripheral mononuclear cells (hPBMCs) was lowered by UCMSCs which had been stimulated by TNF-α or IL-1ß for 3 days. Moreover, IFN-γ and TNF-α secretion level was only inhibited by UCMSCs which had been by stimulated IFN-γ for 3 days but not 7 days. Our data demonstrated that different inflammatory cytokines and the duration of treatment had different effects on the properties of UCMSCs, which might be instructive for clinical pretreatment in cellular therapeutics.

Development of a Xeno-Free Feeder-Layer System from Human Umbilical Cord Mesenchymal Stem Cells for Prolonged Expansion of Human Induced Pluripotent Stem Cells in Culture.

Various feeder layers have been extensively applied to support the prolonged growth of human pluripotent stem cells (hPSCs) for in vitro cultures. Among them, mouse embryonic fibroblast (MEF) and mouse fibroblast cell line (SNL) are most commonly used feeder cells for hPSCs culture. However, these feeder layers from animal usually cause immunogenic contaminations, which compromises the potential of hPSCs in clinical applications. In the present study, we tested human umbilical cord mesenchymal stem cells (hUC-MSCs) as a potent xeno-free feeder system for maintaining human induced pluripotent stem cells (hiPSCs). The hUC-MSCs showed characteristics of MSCs in xeno-free culture condition. On the mitomycin-treated hUC-MSCs feeder, hiPSCs maintained the features of undifferentiated human embryonic stem cells (hESCs), such as low efficiency of spontaneous differentiation, stable expression of stemness markers, maintenance of normal karyotypes, in vitro pluripotency and in vivo ability to form teratomas, even after a prolonged culture of more than 30 passages. Our study indicates that the xeno-free culture system may be a good candidate for growth and expansion of hiPSCs as the stepping stone for stem cell research to further develop better and safer stem cells.