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Table 1 Summary of the important studies on the effects of cerebrospinal fluid on stem cells

From: Cerebrospinal fluid-stem cell interactions may pave the path for cell-based therapy in neurological diseases

Study Source of CSF Primitive cell type Cell type after induction Changes after induced by CSF Cell identification markers Transplantation (Yes or No)
Pandamooz et al., 2013 [15] Allogeneic-rats Endogenous neural stem cell (allogeneic-rat) Neuron-like cells CSF promoted the differentiation of NSCs into neuron-like cells, with the majority to be glial cells and less neurons Nestin, β-tubulin, GAFP, genes No
Yan et al., 2013 [17] Autologous-human (total hip arthroplasty patients) BM-derived MSCs (autologous-human: total hip arthroplasty patients) NSCs Nestin expression from 6 h, peaked at 24 h; NSE expression from 12 h, peaked at 48 h Nestin, NSE, NF, GFAP No
Ren et al., 2015 [18] Autologous-human (neurodegenerative disease patients) BM-derived (autologous-human: neurodegenerative disease patients) and umbilical (allogeneic-human: full-term healthy neonate by eutocia) MSCs NSCs N/A N/A Yes, clinical trial
Ye et al., 2009 [19] Autologous-human (healthy voluntary donors) BM-derived (autologous-human: healthy voluntary donor) and umbilical (allogeneic-human: full-term healthy neonate by eutocia) MSCs NSCs BM-MSCs semiadhered by 24 h, completely or loosely adhered by 48 h with budding, formed spindle-shaped cells with pseudo-foot by 72 h, formed large colonies by 1 week, whorled arrangement by 10 days; umbilical MSCs semiadhered by 24 h, loosely adhered with little budding by 48 h, spindle-like change by 72 h, formed small colonies by 14 days, whorled arrangement by 21 days CD34, CD44, CD45, CD90, β-tubulin, NSE, NF, GFAP No
Ye et al., 2015 [20] Allogeneic-human (healthy voluntary donors) BM-MSCs (allogeneic-rat) Neuron-like cells N/A N/A Yes, animal experiments (rats)
Feng et al., 2015 [21] Allogeneic-human (healthy voluntary donors) BM-MSCs (allogeneic-rat) Neuron-like cells N/A N/A Yes, animal experiments (rats)
Ye et al., 2011 [22] Allogeneic-human (healthy voluntary donors) BM-MSCs (allogeneic-human: healthy voluntary donor) Neuron-like cells After 24 h of induction cells exhibited a significant morphological change including soma retraction and transparency. After 3 days, a number of neurites were formed. The soma of 4-day cultures gradually formed a tapered, triangular and irregular shape. The soma of 7-day cultures was similar to the dendrite and axon-like structure of astrocytes β-Tubulin, GFAP No
Ren et al., 2013 [23] Allogeneic-human (healthy voluntary donors) BM-derived (allogeneic-human: patients with written informed consent for special treatment) and umbilical (allogeneic-human: full-term healthy neonate by eutocia) MSCs NSCs Low β-tubulin positive rates in IHC and IF by 6 h, highest β-tubulin fluorescence and positive rates at 72 h; high GAFP positive rates in IHC and IF that peaked at 48 h, and eventually dropped afterwards, positive double fluorescence staining by 72 h CD34, CD44, CD45, CD90, β-tubulin, GAFP, No
Chen et al., 2016 [24] Allogeneic-human (healthy voluntary adult donors) BM-derived (allogeneic-rat) Neuron-like cells Adherence from 12 h, most cells adhered after 24 h with long spindle shape, apparent colonies formed by 72 h, typical fibroblast-like cells appeared after 6 days CD29, CD45, CD54, CD90, GAFP, NSE No
Ye et al., 2016 [25] Allogeneic-human (healthy voluntary adult donors) BM-derived (allogeneic-rat) Neuron-like cells At day 4 postinduction by CSF, cells were digested with 0.25% trypsin and resuspended to a concentration of 1 × 107 cells/ml NSE, GFAP, BRDU, Yes, animal experiments
Farivar et al., 2015 [26] Allogeneic-human (normal children) Umbilical (allogeneic-fresh human umbilical cords) Neuron-like cells No significant cell death after CSF treatment; a remarkable increase in Nestin expression over 21 days; MAP2 showed a delayed expression on day 21; GFAP is expressed before MAP2, GFAP expression is higher than MAP2 expression on day 14 Nestin, MAP2, GFAP No
Shen et al., 2011 [27] Allogeneic-human (healthy voluntary donors) BM-derived (allogeneic-rat) Neuron-like cells (small round cell) After adherence by 24 h, the number of adherent cells continually increased, with long spindle shapes, exhibited typical fibroblast morphology after ~ 6 days CD29, CD45, CD71, CD90, CD106, NSE No
Zhu et al., 2015 [28] Allogeneic-human Adipose MSCs (allogeneic-human), fetal neural progenitor cells (allogeneic-human) Stem cells Human CSF promoted proliferation, inhibited apoptosis, increased the migration speed and distance of hAMSCs and hfNPCs, enhanced their migration capacity to GBM conditioned media; IGF-1 in human CSF affected the apoptosis and proliferation of hAMSCs and hfNPCs, enhanced the migration capacity and affect the expression of CXCR4 in hAMSCs and hfNPCs CD31, CD34, CD45, CD73, CD90 and CD105 via flow cytometry. NPCs were stained with Nestin, GFAP and Tuj-1.GBM No
Glage et al., 2011 [29] Allogeneic-human BM-derived MSCs (allogeneic-human) Stem cells GLP-1 CSF concentrations can improve stem cell viability N/A Yes, animal experiments (cats)
Yang et al., 2009 [30] Autologous-rat BM-derived (allogeneic-rat) NSCs After transplantation of BM-MSCs, CSF stimulated the differentiation into NSCs, the effect of which was more significant when transplanted earlier, cells generally adhered to the bottom of the plates by 72 h, with cell synapses NF, Nestin Yes, animal experiments (rats)
Wang et al., 2012 [36] Allogeneic-human (amyotrophic lateral sclerosis patients) BM-derived (allogeneic-rat) Neuron-like cells No change on day 1, cells started to shrink from day 4 and cell synapses appeared, synapses increased on day 7 CD29, CD34, CD44, CDE45, NSE, Nestin No
Kim et al., 2015 [37] Allogeneic-human UCB (allogeneic-human) NSCs After CSF induction, UCB-MSCs enhanced the synaptic regeneration of NSCs in the hippocampus and promoted the clearance of Aβ42 N/A Yes, animal experiments (rats)
Bian et al., 2003 [38] Allogeneic-human: (healthy voluntary donors) Embryo (allogeneic-human) Neuron-like cells Adhered after 24–48 h, proliferated and differentiated after 2 days, stabilized after 3 weeks NF, GFAP, Galc No
Chen et al., 2011 [39] Allogeneic-human (healthy voluntary donors), allogeneic-human (closed brain contusion patients) Embryo (allogeneic-human) Neuron-like cells Adhered and differentiated after 2–3 h, adherence peaked by 10 h with increased differentiation GFAP, MAPR, Nestin No
Yin et al., 2010 [40] Allogeneic-human (cerebral palsy children) Embryo (allogeneic-human) Neuron-like cells Cell migrated from 6 hrs, cell clusters formed after 4 days GFAP, NF, Nestin No
Xu et al., 2013 [41] Allogeneic-human (healthy voluntary donors) Embryo (allogeneic-human) Dopaminergic neurons Differentiation was first induced with a certain concentration of ascorbic acid, followed by normal human CSF treatment for inducing the differentiation of stem cells from the embryonic mesencephalon to dopaminergic neurons in order to obtain the maximum proportion of dopaminergic neurons TH No
Zappaterra et al., 2013 [42] Allogeneic-rat Embryo (allogeneic-rat) Neuron-like cells CSF from varying ages or conditions to investigate the biological activity of the CSF proteome on target cells PH3, Tuj1, BRDU Yes-animal experiments (rats)
Martín et al., 2006 [43] Allogeneic-chicken Embryo (allogeneic-chicken) NSCs FGF2 contained within chick E-CSF was involved in regulating the behavior of neuroepithelial stem cells Genes No
Parada et al., 2005 [44] Allogeneic-chicken Embryo (allogeneic-chicken) NSCs The expression of neuroepithelial genes in ESCs was affected by CSF BRDU, genes No
Kiiski et al., 2013 [45] Allogeneic-human (healthy voluntary donors) Embryo (allogeneic-human) Neuron-like cells Human CSF supported neural cell growth whereas artificial CSF was detrimental to the cells; human CSF promoted glial differentiation over neuronal differentiation Nestin, MAP2, GFAP No
Ma et al., 2013 [46] Allogeneic-human (patients) Embryo (allogeneic-rat) NSCs Adult CSF did not support neurogenesis from fetal rat NSCs Nestin, NSE, GFAP No
Buddensiek et al., 2009 [47] Allogeneic-human (patients) Embryo (allogeneic-rat) Neuron-like cells CSF inhibited the differentiation of ESCs into neurons but promoted their differentiation into glial cells Nestin, GFAP, β-tubulin No
Li, 2012 [48] Allogeneic-rat Endogenous neural stem cell (Allogeneic-Rat) NSCs After spinal cord injury, changes of the CSF components affected the proliferation and differentiation of endogenous NSCs BRDU, Nestin No
Liu, 2007 [49] Allogeneic-human (traumatic brain injury patients), allogeneic-human (hydrocephalus patients) Endogenous neural stem cell (Allogeneic-Rat) NSCs 1) NSC could survive, proliferate and differentiate in both the traumatic bloody CSF and hydrocephalic clear CSF. 2) There was faster and higher percentage of adherent differentiation of NSC in traumatic bloody CSF than in hydrocephalic clear CSF. 3) The NSC differentiation types were different when induced by the traumatic bloody CSF and hydrocephalic clear CSF. NSC tended to differentiate into glial cells in traumatic bloody CSF, and into neurons in hydrocephalic clear CSF. Nestin, NSE, GFAP No
Teng et al., 2003 [50] Allogeneic-rat (cerebral ischemia), allogeneic-rat (normal) Endogenous neural stem cell (allogeneic-rat) NSCs CSF of cerebral ischemia rats promoted the survival of NSCs in vitro, and promoted the differentiation of NSCs into neurons and astrocytes Nestin, NSE, GFAP No
Nozaki et al., 1992 [51] Allogeneic-human (subarachnoid hemorrhage patients) Endogenous neural stem cell (allogeneic-human) NSCs The bloody CSF from subarachnoid hemorrhage patients was an effective stimulant for activating and promoting the proliferation and differentiation of endogenous NSCs Genes No
Haines et al., 2015 [52] Allogeneic-human (multiple sclerosis patients) Endogenous neural stem cell (allogeneic-rat) NSCs CSF from multiple sclerosis patients could affect the transcription in oligodendrocyte progenitor cells of NSCs Genes No
Peirouvi et al., 2015 [53] Allogeneic-rat Embryo (allogeneic-rat), endogenous stem cell (allogeneic-rat) Neuron-like cells The proportion of neurons and glial cells differentiated under different pathophysiological states from ESCs at different stages and hippocampal NSCs at different locations was different Nestin, β-tubulin, GAFP, MAP-2, Genes No
Delgado et al., 2014 [54] Allogeneic-rat Endogenous neural stem cell (allogeneic-rat) Neuron-like cells NO-preconditioned rat CSF promoted the proliferation and differentiation of the subependymal nerve cells Nestin, BRDU, GAFP, genes No
Cristofanilli et al., 2013 [55] Allogeneic-human (multiple sclerosis patients) Endogenous neural stem cell (allogeneic-human) Neuron-like cells CSF of patients with progressive multiple sclerosis promoted the differentiation of human NSCs into neurons and oligodendrocytes, but the ratio was different MAPR, TUJ1, GFAP, genes No
Buddensiek et al., 2010 [56] Allogeneic-human Endogenous neural stem cell (allogeneic-human) Neuron-like cells Under different conditions, CSF mainly promoted NSC gliosis, occasionally neuron-like differentiation was mainly observed BRDU, GFAP, genes No
Wang et al., 2016 [57] Allogeneic-rats Endogenous neural stem cell (allogeneic-rat) Neuron-like cells CSF containing traditional Chinese medicine induced the increment and differentiation of endogenous nerve cells, and the cell vitality and the disease resistance were stronger Tubulin, GFAP, genes No
  1. amyloid beta-peptide, BM bone marrow, BRDU bromodeoxyuridine, CSF cerebrospinal fluid, E-CSF embryonic cerebrospinal fluid, ESC embryonic stem cell, FGF2 basic fibroblast growth factor2, Galc galactocerebrosidase, GBM glioblastoma multiforme, GFAP glial fibrillary acidic protein, GLP-1 glucagon-like peptide-1, hAMSC human amniotic mesenchymalstem cells, hfNPC human fetal neural progenitor cell, IF immunofluorescence, IGF-1 insulin-like growth factor-1, IHC immunohistochemistry, MAP2 microtubule-associated protein 2, MAPR membrane-associated progesterone receptor, MSC mesenchymal stromal cell, N/A not available, NF neurotrophic factor, NSC neural stem cell, No No transplantation, NSE neuron-specific enolase, PH3 phosphorylated histone H3, TH Tyrosine hydroxylase, Tuj1 neuronal class III β-Tubulin, UCB umbilical cord blood