Lithium chloride improves the efficiency of induced pluripotent stem cell-derived neurospheres

Abstract

Induced pluripotent stem cell (iPSC)-derived neurospheres, which consist mainly of neural progenitors, are considered to be a good source of neural cells for transplantation in regenerative medicine. In this study, we have used lithium chloride, which is known to be a neuroprotective agent, in an iPSC-derived neurosphere model, and examined both the formation rate and size of the neurospheres as well as the proliferative and apoptotic status of their contents. Our results showed that lithium enhanced the formation and the sizes of the iPSC-derived neurospheres, increased the number of Ki67-positive proliferating cells, but reduced the number of the TUNEL-positive apoptotic cells. This increased number of Ki67 proliferating cells was secondary to the decreased apoptosis and not to the stimulation of cell cycle entry, as the expression of the proliferation marker cyclin D1 mRNA did not change after lithium treatment. Altogether, we suggest that lithium enhances the survival of neural progenitors and thus the quality of the iPSC-derived neurospheres, which may strengthen the prospect of using lithium-treated pluripotent cells and their derivatives in a clinical setting.

Lithium increases proliferation of hippocampal neural stem/progenitor cells and rescues irradiation-induced cell cycle arrestin vitro

“…2B ). These data support previous studies where lithium was found to increase neurosphere growth in vitro , hence ruling out the possibility that this treatment may be sensitizing NSPCs in the developing brain to irradiation [ 36 , 61 ]. Lithium has previously been observed to radio-sensitize cancerous cells and at the same time protect NSPCs, possibly due to lithium acting on genes with multifunctional roles in distinct DNA repair pathways, which are frequently aberrant in cancer [ 35 , 62 ].…”

“…In agreement with previous studies, we found that lithium, applied as a pre-treatment and maintained after irradiation, moderately decreased DNA damage (γH2AX) and recruited a significant proportion of NSPCs into proliferation [ 31 ]. However, in contrast to previous reports we did not find any evidence of lithium preventing young NSPCs from irradiation-induced apoptosis, as judged by annexin V and Sub-G 1 cell cycle analysis [ 34 , 36 ].…”

Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson’s disease model

“…Recently, an efficient and simple method to induce the stem cell differentiation was reported. Lithium (Li), the smallest alkali metal with an atomic weight of 6.9, was found to enhance the efficiency of induced pluripotent stem cell-derived neurospheres (Tafreshi et al 2015), promote the odontoblast differentiation of hair follicle neural crest cells (Shan et al 2015), modulate the proliferation and differentiation of mesenchymal stem cells (Dong et al 2015;Tang et al 2015), prevent neural progenitor cell apoptosis (Cabrera et al 2014). These studies indicated that Lithium may play function in the NSCs' differentiation.…”