Human EnSC (endometrial-derived stem cell) is an abundant and easily available source for cell replacement therapy. Many investigations have shown the potency of the cells to differentiate into several mesoderm-derived cell lineages, including osteocytes and adipocytes. Here, the potency of EnSC in neural differentiation has been investigated. Flow cytometric analysis showed that they were positive for CD90, CD105, OCT4, CD44 and negative for CD31, CD34, CD133. The characterized cells were induced into neural differentiation by bFGF (basic fibroblast growth factor), PDGF (platelet-derived growth factor) and EGF (epidermal growth factor) signalling molecules, respectively in a sequential protocol, and differentiated cells were analysed for expression of neuronal markers by RT–PCR (reverse transcription–PCR) and immunocytochemistry, including Nestin, GABA (γ-aminobutyric acid), MAP2 (microtubule-associated protein 2), β3-tub (class III β-tubulin) and NF-L (neurofilament-light) at the level of their mRNAs. The expression of MAP2, β3-tub and NF-L proteins in EnSC was confirmed 28 days PT (post-treatment) by immunocytochemistry. In conclusion, EnSC can respond to signalling molecules that are usually used as standards in neural differentiation and can programme neuronal cells, making these cells worth considering as a unique source for cell therapy in neurodegenerative disease.

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Many people worldwide suffer from motor neuron-related disorders such as amyotrophic lateral sclerosis and spinal cord injuries. Recently, several attempts have been made to recruit stem cells to modulate disease progression in ALS and also regenerate spinal cord injuries. Chorion-derived mesenchymal stem cells (C-MSCs), used to be discarded as postpartum medically waste product, currently represent a class of cells with self renewal property and immunomodulatory capacity. These cells are able to differentiate into mesodermal and nonmesodermal lineages such as neural cells. On the other hand, gelatin, as a simply denatured collagen, is a suitable substrate for cell adhesion and differentiation. It has been shown that electrospinning of scaffolds into fibrous structure better resembles the physiological microenvironment in comparison with two-dimensional (2D) culture system. Since there is no report on potential of human chorion-derived MSCs to differentiate into motor neuron cells in two- and three-dimensional (3D) culture systems, we set out to determine the effect of retinoic acid (RA) and sonic hedgehog (Shh) on differentiation of human C-MSCs into motor neuron-like cells cultured on tissue culture plates (2D) and electrospun nanofibrous gelatin scaffold (3D).

Extracellular vesicles (EVs) are membrane-bound vesicles, including exosomes and microvesicles. EVs are nanometer sized, found in physiological fluids such as urine, blood, cerebro-spinal fluid (CSF), with a capacity of transferring various biological materials such as microRNAs, proteins, and lipids among cells without direct cell-to-cell contact. Many cells in the nervous system have been shown to release EVs. These vesicles are involved in intercellular communication and a variety of biological processes such as modulation of immune response, signal transduction, and transport of genetic materials with low immunogenicity; therefore, they have also been recently investigated for the delivery of therapeutic molecules such as siRNAs and drugs in the treatment of diseases. In addition, since EV components reflect the physiological status of the cells and tissues producing them, they can be utilized as biomarkers for early detection of various diseases. In this review, we summarize EV application, in diagnosis as biomarker sources and as a carrier tool for drug delivery in EV-based therapies in neurodegenerative diseases.

Human bone marrow-derived mesenchymal stem cells are potent types of cells with self renewal ability and immunomodulatory properties. They not only have the capacity to differentiate into mesodermal lineages, but they are also capable to transdifferentiate into neural cells in vitro and in vivo. From a biological point of view, the specification of cell fate in the central nervous system is largely dictated by retinoic acid and sonic hedgehog. In addition with inductive molecules, electrospun three dimensional (3D) scaffolds with similar properties to natural extracellular matrix represent a physiological environment that could better resemble the in vivo microenvironment in comparison with two dimensional culture systems. In this regard, the aim of this study was to examine whether induction of human BM-MSCs with retinoic acid (RA) and sonic hedgehog (Shh) in combination with electrospun gelatin scaffold could lead to better differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) into motorneuron-like cells in vitro.