Differentiation of Human Mesenchymal Stem Cells towards Neuronal Lineage: Clinical Trials in Nervous System Disorders

Abstract

Mesenchymal stem cells (MSCs) have been proposed as an alternative therapy to be applied into several pathologies of the nervous system. These cells can be obtained from adipose tissue, umbilical cord blood and bone marrow, among other tissues, and have remarkable therapeutic properties. MSCs can be isolated with high yield, which adds to their ability to differentiate into non-mesodermal cell types including neuronal lineage both in vivo and in vitro. They are able to restore damaged neural tissue, thus being suitable for the treatment of neural injuries, and possess immunosuppressive activity, which may be useful for the treatment of neurological disorders of inflammatory etiology. Although the long-term safety of MSC-based therapies remains unclear, a large amount of both pre-clinical and clinical trials have shown functional improvements in animal models of nervous system diseases following transplantation of MSCs. In fact, there are several ongoing clinical trials evaluating the possible benefits this cell-based therapy could provide to patients with neurological damage, as well as their clinical limitations. In this review we focus on the potential of MSCs as a therapeutic tool to treat neurological disorders, summarizing the state of the art of this topic and the most recent clinical studies.

Differentiation of Human Mesenchymal Stem Cells from Wharton’s Jelly Towards Neural Stem Cells Using a Feasible and Repeatable Protocol

“…Moreover, many studies have found the expression of MAP2, but only after subsequent differentiation of derived NSC-like cells [56,72]. The discrepancies in the mentioned results might be a result of variable biological features of the cells according to their source, the donor, and the culture conditions [96,97]. However, a recent comparative analysis highlighted that the source of MSCs has a greater influence than the culture conditions applied for neural induction.…”

Role of Mesenchymal Stem Cells in Counteracting Oxidative Stress—Related Neurodegeneration

“…To clarify the choice to focus our attention on mesenchymal stem cells application in neurodegenerative diseases, a whole picture of different stem cells characteristics, with advantages and drawbacks, is reported below. Stem cells can be categorized as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), fetal stem cells (FSCs), perinatal stem cells (PSCs), and adult stem cells (ASCs) [126]. ESCs are pluripotent stem cells isolated from the inner cell mass of blastocysts before the stage of gastrulation [127,128].…”

Neurons from human mesenchymal stem cells display both spontaneous and stimuli responsive activity

“…Various strategies have been developed over the years to transdifferentiate MSCs into neurons. Inducers used in these strategies are generally divided into four groups: small molecules, epigenetic modifications, psychotropic drugs and enriched media (medium coctails with chemical inducers) [12]. Alternatively, differentiation of neurons from MSCs was reported in different ways such as using co-culture conditions, exosomes and graphene substrates [13][14][15].…”