Human endometrial stem cell neurogenesis in response to NGF and bFGF

Abstract

The potential of cell therapy is promising in nerve regeneration, but is limited by ethical considerations about the proper and technically safe source of stem cells. We report the successful differentiation of human EnSCs (endometrial stem cells) as a rich source of renewable and safe progenitors into high-efficiency cholinergic neurons. The extracellular signals of NGF (nerve growth factor) and bFGF (basic fibroblast growth factor) could induce cholinergic neuron differentiation. ChAT (choline acetyltransferase), MAP2 (microtubule associated protein 2) and NF-l (neurofilament L) increased after administration of bFGF and NGF to the EnSC cultures. trkC and FGFR2 (fibroblast growth factor receptor 2), which belong to the NGF and bFGF receptors respectively, were determined in populations of EnSCs. NGF, bFGF and their combination differentially influenced human EnSCs high efficiency differentiation. By inducing cholinergic neurons from EnSCs in a chemically defined medium, we could produce human neural cells without resorting to primary culture of neurons. This in vitro method provides an unlimited source of human neural cells and facilitates clinical applications of EnSCs for neurological diseases.

Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

“…They expand rapidly and they have fewer technical and ethical problems so they have great potential as therapeutic agents and autologous grafts [2]. Our team has previously shown that the endometrial stem cells could be differentiated successfully into other lineages of cells especially neural cells [1, 11]. It represents a progress in the development of a new source of neurons.…”

“…The hEnSCs treated with FLX and FLX + 10  μ M PI3-K inhibitor (LY294002, Promega, USA) were fixed by incubation in 9% paraformaldehyde for 20 min and permeabilized with 0.5% Triton X-100 for 10 min as described previously [1]. The cells were then reacted with primary antibodies for Nestin (Sigma, USA), MAP-2 (Sigma, USA), β -tubulin-III (Chemicon, USA), and CD11b as a glial marker (Millipore, USA) at 4°C for 12 h, washed with PBS and reacted with the fluorescent isothiocyanate (FITC) conjugated secondary antibody (Sigma, USA) at room temperature for 2 h. Finally, the cells were washed with PBS three times, and DAPI was used for DNA staining.…”

“…Cell therapy will be an effective strategy for treating neurodegenerative diseases and spinal cord injuries [1]. However the important part of the successful therapy depends on differentiation and promoting the survival of implanted cells.…”

Neuroprotective Effect of Transplanted Neural Precursors Embedded on PLA/CS Scaffold in an Animal Model of Multiple Sclerosis

“…Neurotrophins are expressed in the peripheral and central target fields of neurons during development and promote the survival of neurons [9,10]. Prior studies showed that NGF accelerated the proliferation and differentiation of neural progenitor cells in conjunction with basic fibroblast growth factor (bFGF) and promoted the survival of neurons [11,12].…”

The Endometrium as a Source of Mesenchymal Stem Cells for Regenerative Medicine1

“…Upon stimulation with nerve growth factor (NGF) and bFGF, HEDSC increased expression of choline acetyl transferase, microtubule associated protein 2 (MAP2), and neurofilament L, while demonstrating neuron-like morphology. However, detailed electrophysiological studies and thorough characterization of the differentiated cells have not yet been completed [65].…”