The Potential of Fibroblast Transdifferentiation to Neuron Using Hydrogels

Currently there is a big drive to generate neurons from differentiated cells which would be of great benefit for regenerative medicine, tissue engineering and drug screening. Most studies used transcription factors, epigenetic reprogramming and/or chromatin remodeling drugs which might reflect incomplete reprogramming or progressive deregulation of the new program. In this review, we present a potential different method for cellular reprogramming/transdifferentiation to potentially enhance regeneration of neurons. We focus on the use of biomaterials, specifically hydrogels, to act as non-invasive tools to direct transdifferentiation, and we draw parallel with existing transcriptional and epigenetic methods. Hydrogels are attractive materials because the properties of hydrogels can be modified, and various natural and synthetic substances can be employed. Incorporation of extracellular matrix (ECM) substances and composite materials allows mechanical properties and degradation rate to be controlled. Moreover, hydrogels in combinations with other physical and mechanical stimuli such as electric current, shear stress and tensile force will be mentioned in this review.

Latent tri-lineage potential of human menstrual blood-derived mesenchymal stromal cells revealed by specific in vitro culture conditions

Human menstrual blood-derived mesenchymal stromal cells (MenSCs) have become not only an important source of stromal cells for cell therapy but also a cellular source for neurologic disorders in vitro modeling. By using culture protocols originally developed in our laboratory, we show that MenSCs can be converted into floating neurospheres (NSs) using the Fast-N-Spheres medium for 24-72h, and can be transdifferentiated into functional dopaminergic-like (DALNs, ~26% TH+/DAT+ flow cytometry) and cholinergic-like neurons (ChLNs, ~46% ChAT+/VAChT flow cytometry) which responded to dopamine- and acetylcholine- triggered neuronal Ca 2+ inward stimuli when cultured with the NeuroForsk and the Cholinergic-N-Run medium , respectively in a timely fashion (i.e., 4-7 days). Here, we also report a direct transdifferentiation method to induce MenSCs into functional astrocyte-like cells (ALCs) by incubation of MenSCs in commercial Gibco® Astrocyte Medium in 7-days. The MSCs-derived ALCs (~59% GFAP+/S100b+) were found to respond to glutamate-induced Ca 2+ inward stimuli. Altogether these results show that MenSCs are a reliable source to obtain functional neurogenic cells to further investigate the neurobiology of neurologic disorders.

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour.