Signals in pathological CNS extracts of ALS mice promote hMSCs neurogenic differentiation in vitro.
The capability of MSCs to differentiate into neurons has been proven by many studies. Recently, other studies have cast doubt on MSCs neurogenic differentiation with non-physiological chemical inducing agents in vitro. This present study was designed to use conditioned medium to investigate whether signals from pathological condition of ALS were competent to induce a program of neurogenic differentiation in expanded cultures of hMSCs. Incubation of hMSCs with conditioned medium prepared from CNS extracts of ALS mice (SOD1-G93A ALS mice) resulted in a time-dependent morphological change from fibroblast-like into neuron-like, concomitant with increase in the expression of Nestin and subsequent beta-tubulin III, NSE and GAP43. Moreover, signals in pathological CNS extracts of ALS mice were more effective in promoting hMSCs neurogenic differentiation than those in physiological extracts of normal adult mice. These results show that pathological condition of ALS is endowed with capacity to induce hMSCs neurogenic differentiation and hMSCs have shown a potential candidate in cellular therapy for ALS.
Zhao
Cui-Ping
CP
Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China.
Zhang
Cheng
C
Wang
Yi-Hua
YH
Zhou
Sheng-Nian
SN
Zhou
Chang
C
Li
Wan-Yi
WY
Yu
Mei-Juan
MJ
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002490:Central Nervous System / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism*; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D013482:Superoxide Dismutase / Q000235:genetics; D014404:Tubulin / Q000378:metabolism
D017077:Culture Media, Conditioned; D019922:GAP-43 Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D014404:Tubulin; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase