Fetal Cerebrospinal Fluid Promotes Proliferation and Neural Differentiation of Stromal Mesenchymal Stem Cells Derived from Bone Marrow

Abstract

Embryonic cerebrospinal fluid (E-CSF) contains many neurotrophic and growth factors, acts as a growth medium for cortical progenitors, and can modulate proliferation and differentiation of neural stem cells. Mesenchymal stem cells (MSCs) are multipotential stem cells that can differentiate into several types of mesenchymal cells as well as nonmesenchymal cells, such as neural cells. In the present study, the effect of E-CSF on proliferation and neural differentiation of bone marrow mesenchymal stem cells (BM-MSCs) was investigated to test whether E-CSF is capable of driving these cells down the neuronal line. To verify the multipotential characteristics of BM-MSCs, the cells were analyzed for their osteogenic and adipogenic potential. Expression of the neural markers, MAP-2 and β-III tubulin, was determined by Immunocytochemistry. BM-MSCs differentiate into neuronal cell types when exposed to b-FGF. BMMSCs cells cultured in medium supplemented with CSF showed significantly elevated proliferation relative to control cells in media alone. E-CSF (E17-E19

Deciphering the impact of cerebrospinal fluid on stem cell fate as a new mechanism to enhance clinical therapy development

“…Different effect of CSF on stem cells has been also observed depending on their origin. Shokohi et al (2017) observed that CSF affected the expression of marker MAP2 (increase) in murine BM-MSCs, but did not affect MSCs derived from dental pulp (Haratizadeh et al, 2017). In addition, rat CSF increased the expression of the neural marker Nestin in dental pulp MSCs (Haratizadeh et al, 2017) and rat BM-MSCs (Mafikandi et al, 2019).…”

“…Culturing bone marrow mesenchymal stem/stromal cells (BM-MSCs) in CSF resulted in morphological changes to present astrocyte dendrite and axon-like cells [human CSF and human BM-MSCs; (Ye et al, 2011;Ge et al, 2015)] neurite length [rat CSF and murine BM-MSCs; (Shokohi et al, 2017)]; long spindle-shaped cells [rat CSF and rat BM-MSCs; (Mafikandi et al, 2019)]; mature neurons and dendrite-like cells presenting Nissl bodies [rabbit CSF and rabbit BM-MSCs; (Otify et al, 2014)]. Moreover, CSF from newborn rats of healthy mothers (N-CSF, normal-CSF) has been shown to undergo more rapid morphological change into long spindle-shaped cells than CSF from newborn rats of mothers with hypothyroidism (HTH-CSF, hypothyroidism-cerebrospinal fluid) (Mafikandi et al, 2019).…”

“…Moreover, CSF from newborn rats of healthy mothers (N-CSF, normal-CSF) has been shown to undergo more rapid morphological change into long spindle-shaped cells than CSF from newborn rats of mothers with hypothyroidism (HTH-CSF, hypothyroidism-cerebrospinal fluid) (Mafikandi et al, 2019). The presence of CSF (human and rat) increased protein expression of β-III-tubulin in human (Ye et al, 2011;Ge et al, 2015) and murine BM-MSCs (Shokohi et al, 2017). Moreover, an increased GFAP expression has been observed [in human and rabbit CSF; (Ye et al, 2011;Otify et al, 2014;Ge et al, 2015)].…”

Effects of maternal thyroid hormone deficiency on differentiation of mesenchymal stem cells in CSF-exposed neonatal Wistar rats

“…The cell suspension was then centrifuged at 15000 rpm for 5 min, and subsequently cultured in 25 cm 2 flasks. The adhered cells from the third passage were used to be treated with CSF (Shokohi et al, 2017).…”

“…To determine the most effective concentration of CSF, cells cultured in DMEM, 3% FBS and 1% pen/ strep were exposed to different concentrations of CSF [i.e., 5 ,7 and 10 /100 (v/v)] for a week. One concentration was selected as yielding the optimum CSF concentration (Shokohi et al, 2017).…”