Performance and Mechanism of Neuroleukin in the Growth and Survival of Sertoli Cell-Induced Neurons in a Coculture System

Abstract

Sertoli cells (SCs), which are recognized as the "nurse cells" of the testis due to their important biofunctions, have been used in cotransplantation with neurons in cell therapy. However, it is not clear whether SCs influence neuronal communication and survival. In this study, we showed that approximately 60% of cortical neural stem cells (NSCs) cocultured with SCs differentiated into mature neurons. In addition, the neurite outgrowth and neuronal survival rates were significantly enhanced in the coculture system compared with differentiated neurons induced by a differentiation medium. The neuroleukin (NLK) secretion of SCs was also identified at the RNA and protein level, and the roles of NLK in neuromorphology and physiological regulation were systematically investigated for the first time. These results not only highlight the significance of paracrine regulation of NSCs by SCs but also confirm the role NLK plays in the differentiation and survival of NSCs. Finally, we proposed a possible hypothesis for the mechanism of NLK in the growth and survival of SC-induced neurons based on Western blotting results, which is that NLK secreted by SCs activates the Ras/Raf/MEK/Erk, Jak/Stat, and PI3K/Akt pathways, but not the NF-κB pathway, in neurons resulting in their growth and survival.

Identification of Sertoli cell-specific transcripts in the mouse testis and the role of FSH and androgen in the control of Sertoli cell activity

“…Interestingly, the one KEGG pathway significantly enriched is for axon guidance while biological processes associated with neural signalling are also enriched. This is consistent with the reported ability of Sertoli cells to promote neuronal differentiation and survival in co-cultures and co-grafts [ 39 ] although the normal physiological importance of this is not clear beyond the high potential for the Sertoli cells to secrete trophic factors.…”

Sertoli cells for cell transplantation: pre‐clinical studies and future perspectives

“…In particular, SCs were co‐cultured with dopaminergic fetal neurons in vitro inducing not only an increase in cell viability but also an enhancement of the differentiation toward the neuronal cell phenotype from the multipotent stem cell line of midbrain tissue (Othberg et al ., ; Shamekh et al ., ). Moreover, neuronal survival and outgrowth of neurites significantly increased in cells co‐cultured SCs cells, as compared with neurons whose differentiation depended on appropriate culture medium (Deng et al ., ). Either xeno‐ or allotransplantation of SCs into striatal‐damaged rat brains, an experimental model of Parkinson's disease (PD), led to a regenerative action surrounding the implantation site.…”

Cryopreserved CD90+ cells obtained from mobilized peripheral blood in sheep: a new source of mesenchymal stem cells for preclinical applications

“…However, MSCs isolation and characterization in MPB in sheep has been sparsely studied (Juthier et al 2006 ), and the majority of what has been described in the literature has been focused on the obtaining and characterization of hematopoietic stem cells (Almeida-Porada et al 2007 ; Porada et al 2008 ). Isolation of MSCs in MPB had been previously reported in a variety of mammalian species including pigs (Harn et al 2013 ), rabbits (Fu et al 2014 ), dogs (Thomasson et al 2003 ), mice (Lee et al 2014 ), rats (Deng et al 2014 ), and humans (Kang et al 2014 ).…”