Matrix Cells from Wharton's Jelly Form Neurons and Glia

Abstract

We have identified an easily attainable source of primitive, potentially multipotent stem cells from Wharton's jelly, the matrix of umbilical cord. Wharton's jelly cells have been propagated in culture for more than 80 population doublings. Several markers for stem cells, including c-kit (CD117), and telomerase activity are expressed in these cells. Treatment with basic fibroblast growth factor overnight and low-serum media plus butylated hydroxyanisole and dimethylsulfoxide induced Wharton's jelly cells to express a neural phenotype. Within several hours of this treatment, Wharton's jelly cells developed rounded cell bodies with multiple neurite-like extensions, similar to the morphology of neural stem cells. Neuron-specific enolase (NSE), a neural stem cell marker, was expressed in these cells, as shown by immunocytochemistry. Immunoblot analysis showed similar levels of NSE expression in both untreated and induced Wharton's jelly cells. After 3 days, the induced Wharton's jelly cells resembled bipolar or multipolar neurons, with processes that formed networks reminiscent of primary cultures of neurons. The neuron-like cells in these cultures stained positively for several neuronal proteins, including neuron-specific class III beta-tubulin, neurofilament M, an axonal growth-cone-associated protein, and tyrosine hydroxylase. Immunoblot analysis showed increasing levels of protein markers for mature neurons over time post induction. Markers for oligodendrocytes and astrocytes were also detected in Wharton's jelly cells. These exciting findings show that cells from the matrix of umbilical cord have properties of stem cells and may, thus, be a rich source of primitive cells. This study shows their capacity to differentiate into a neural phenotype in vitro.

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

“…It was also described that MSCs do not require oxidative phosphor-ylation to survive ( Dos Funes et al, 2007) instead, hypoxia prolongs the lifespan of these cells, increases their proliferative capacity and reduces differentiation ( Fehrer et al, 2007). Several studies in recent years investigated the biological activity of HMSCs and their in vitro differentiation in neuroglial-like cells Mitchell et al, 2003). In this study, HMSCs were in vitro differentiated with neurogenic med-ium.…”

“…After 96 h the regular mesenchymal-like shape of the cells changed and the cells became exceedingly long. Morphologically it was observed the formation of neuroglial-like cells after differentiation which were positively stained for the typical specific neuronal markers ( Choong et al, 2007;Fu et al, 2004;Mitchell et al, 2003) such as the GFAP, the GAP-43 and the NeuN attesting a clear successful differentiation. The morphologic and biochemical characteristics of neuroglial-like cells are already described but the mechanism by which stem cells differentiate into neuroglial-like cells is still unknown.…”

“…Different harvesting procedures have led to UC-derived cells that exhibit a neuronal phenotype ( Fu et al, 2006;Mitchell et al, 2003;Sarugaser et al, 2005;Wang et al, 2004) and have potential utility in treatment of neurodegenerative diseases ( Weiss et al, , 2006, indicating the versatility of this cell source. Inter-estingly, these cells, which are major histocompatibility complex (MHC) class II negative, not only express immunoprivileged and immunomodulatory phenotype, but also their MHC class I expres-sion levels can be manipulated ( Sarugaser et al, 2005), making them a potential cell source for MSC-based therapies.…”

Updates on stem cells and their applications in regenerative medicine

“…Umbilical cord blood is a source of both pluripotent stem cells (Kogler et al, 2004) and haematopoietic stem cells. The umbilical cord matrix was found to be a source of multipotent stem cells (Mitchell et al, 2003, Wang et al, 2004. When transplanted to an allo-recipient, these cells show low immunogenicity and can even have localized immunosuppressive functions.…”

Human umbilical cord-derived mesenchymal stem cells differentiate into epidermal-like cells using a novel co-culture technique

“…Previous studies have reported the in vitro differentiation of hUCMSCs into mesoderm-type cells, such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, skeletal muscle cells, and endothelial cells Conconi et al 2006;Hoerstrup et al 2002;Sarugaser et al 2005;Schmidt et al 2006;Wang et al 2004;Wu et al 2007) as well as cells of nonmesoderm lineages, including neurocytes (Wang et al 2004;Fu et al 2004;Ma et al 2005;Mitchell et al 2003). hUC blood-derived MSCs enhanced wound healing in mice by differentiating into keratinocytes (Luo et al 2010).…”