Purmorphamine as a Shh Signaling Activator Small Molecule Promotes Motor Neuron Differentiation of Mesenchymal Stem Cells Cultured on Nanofibrous PCL Scaffold

Abstract

There is variety of stem cell sources but problems in ethical issues, contamination, and normal karyotype cause many limitations in obtaining and using these cells. The cells in Wharton's jelly region of umbilical cord are abundant and available stem cells with low immunological incompatibility, which could be considered for cell replacement therapy. Small molecules have been presented as less expensive biologically active compounds that can regulate different developmental process. Purmorphamine (PMA) is a small molecule that, according to some studies, possesses certain differentiation effects. In this study, we investigated the effect of the PMA on Wharton's jelly mesenchymal stem cell (WJ-MSC) differentiation into motor neuronal lineages instead of sonic hedgehog (Shh) on PCL scaffold. After exposing to induction media for 15 days, the cells were characterized for expression of motor neuron markers including PAX6, NF-H, Islet1, HB9, and choline acetyl transferase (ChAT) by quantitative reverse transcription (PCR) and immunocytochemistry. Our results demonstrated that induced WJ-MSCs with PMA could significantly express motor neuron markers in RNA and protein levels 15 days post induction. These results suggested that WJ-MSCs can differentiate to motor neuron-like cells with PMA on PCL scaffold and might provide a potential source in cell therapy for nervous system.

Conductive hydrogel based on chitosan-aniline pentamer/gelatin/agarose significantly promoted motor neuron-like cells differentiation of human olfactory ecto-mesenchymal stem cells

“…In another study, Ebrahimi-Barough et al suggested PLGA nanofiber scaffolds as a suitable substrate to induce the human endometrial stem cells into MN-like cells [70]. Although other researchers have also been differentiated stem cells into motor neurons on different scaffolds in several previous studies [71,72], there is no report investigating the effect of conductive hydrogels on MN differentiation. Here, to confirm the real-time PCR results immunofluorescent staining and flow cytometry analysis were used to examine the expression of MN specific markers at protein levels.…”

Differentiation of Motor Neuron-Like Cells from Tonsil-Derived Mesenchymal Stem Cells and Their Possible Application to Neuromuscular Junction Formation

“…Therefore, adult stem cells, such as MSCs, are a suitable source of cells for stem cell therapy and may be used to promote the neuromuscular regeneration of patients with MND. Several studies have reported that the MSCs from the umbilical cord, bone marrow, Wharton’s jelly, and dental pulp can differentiate into MNs [20,21,22,23]. However, there was no definite evidence that MSC-derived MNs is functionally active.…”

Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF–kappa B signaling pathway

“…Compared to other tissue engineering scaffolds, electrospun nanofibers exhibit several advantages, such as high surface area and high porosity. By adjusting the solution parameters and spinning conditions, electrospinning can easily control the fiber properties, including the diameter, structure, surface and mechanical properties of the fibers for constructing scaffolds to facilitate the differentiation of stem cells into different types of cells including osteoblasts [17], neuronal cells [18], chondrocytes [19], and cardiomyocytes [20]. PCL can be easily synthesized with polytetrahydrofuran (PTHF) to form PCL-PTHF copolymers [21].…”