Brain‐derived neurotrophic factor facilitates maturation of mesenchymal stem cell‐derived dopamine progenitors to functional neurons

Abstract

The generation of dopamine (DA) neurons from stem cells holds great promise in the treatment of Parkinson’s disease and other neural disease associated with dysfunction of DA neurons. Mesenchymal stem cells (MSCs) derived from the adult bone marrow show plasticity with regards to generating cells of other germ layers. In addition to reduced ethical concerns, MSCs could be transplanted across allogeneic barriers, making them desirable stem cells for clinical applications. We have reported on the generation of DA cells from human MSCs using sonic hedgehog (SHH), fibroblast growth factor 8 and basic fibroblast growth factor. Despite the secretion of DA, the cells did not show evidence of functional neurons, and were therefore designated DA progenitors. Here, we report on the role of brain‐derived neurotrophic factor (BDNF) in the maturation of the MSC‐derived DA progenitors. 9‐day induced MSCs show significant tropomyosin‐receptor‐kinase B expression, which correlate with its ligand, BDNF, being able to induce functional maturation. The latter was based on Ca2+ imaging analyses and electrophysiology. BDNF‐treated cells showed the following: increases in intracellular Ca2+ upon depolarization and after stimulation with the neurotransmitters acetylcholine and GABA and, post‐synaptic currents by electrophysiological analyses. In addition, BDNF induced increased DA release upon depolarization. Taken together, these results demonstrate the crucial role for BDNF in the functional maturation of MSC‐derived DA progenitors.

Resveratrol Protects Human Endothelium from H2O2-Induced Oxidative Stress and Senescence via SirT1 Activation

“…SirT1, which resides in the nucleus, binds and deacetylates p53, NF-B, and forehead transcription factors, as well as histones 13) . SirT1 is postulated to protect against neurodegeneration and diabetes but may promote tumorigenesis [14][15][16] . Its role in disease progression and aging in mammals remains to be further evaluated.…”

Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongationin vitroand promotes nerve fiber regeneration in transected spinal cord injury

“…Previous studies demonstrated that SCs were able to induce neural differentiation of MSCs,29, 37 probably due to their remarkable capacity of cytokines secreting such as brain derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), basic fibroblast growth factor (bFGF) and glial cell line‐derived neurotrophic factor (GDNF),38 which were considered to be effective trophic factors for neural induction of MSCs 28, 39. Compared with our previous 2D study,29 MSCs on a gelatin sponge scaffold resulted in more neuronal differentiation under the SCs induction.…”

Developmental Regulation ofTAC1in Peptidergic-Induced Human Mesenchymal Stem Cells: Implication for Spinal Cord Injury in Zebrafish

“…A dult and embryonic stem cells have the potential to repair, replace, and protect tissues [1][2][3][4]. Adult stem cells have reduced ethical issues and appear to show lower probability of tumor formation [5,6].…”

“…Adult stem cells have reduced ethical issues and appear to show lower probability of tumor formation [5,6]. Mesenchymal stem cells (MSCs) are easy to expand, are responsive to any microenvironment, and can be transplanted across allogeneic barrier [3]. MSCs are ubiquitous; in adults, they are mostly present in bone marrow and adipose tissue [7][8][9].…”