Physiologically based microenvironment for in vitro neural differentiation of adipose-derived stem cells

Table 2 Effects of chemicals-enriched microenvironment on adipose stem cells fate

Action	Chemicals/drugs	Profile	Recognized function	Effects on ASCs
Antioxidant	β-mercaptoethanol	Water-soluble thiol used as a reducing agent for disulfide bonds to protect sulfhydryl groups from oxidation	In peripheral intestinal nervous system increases the number of synapses and the vesicle population in the nerve terminals[69]	Key elements for the neural induction medium: Reduction of oxidative stress and reactive oxygen species production could support neural population
			Improve meiotic maturation in vitro cultured oocytes[70]
	Butylated hydroxyanisole	Mixture of two isomeric organic compounds	Inhibition of 17 β-estradiol(E2)-mediated oxidative stress and of oxidative DNA damage
	N-acetyl-l-cysteine	Synthetic derivative of endogenous amino acid, L-cysteine, precursor of the antioxidant enzyme Glutathione	Stimulator of glutathione synthase Activator of NMDA1 receptor	When co-administrated, reduction of ASCs-doubling time and increase of cell number compared with b-FGF alone supplementation[66]
	Ascorbic acid-2-phosphate (Vitamin C)	Water-soluble essential vitamin	Reducing agent and coenzyme in several metabolic pathways
Interference on DNA	Valproic acid	Branch-chained fatty acid, acting as a histone deacetylase inhibitor	Wide range of neuroprotection[71,72] Inhibitor of glycogen synthase kinase-3[73] Inducer of chromatin remodeling[74]	Promoter of neuron-like cells[75] In vivo, it improves homing of ASCs via overexpression of CXCR4 and CXCR6[76]
	5-azacytidine	Analog of cytidine nucleoside, acting as demethylating agent[77,78]	Inducer of cell plasticity and active molecule for cellular differentiation into multiple phenotype[79]	Stimulated-cells ameliorate neurological deficits when injected in rats after cerebral ischemia[80]
Anti-inflammation	Indomethacin	Synthetic nonsteroidal indole derivative	Inhibitor of COX1/2	Component of neural induction medium applied for two weeks[44]
Immuno modulation	Hydrocortisone	Glucocorticoid hormone	Suppressor of cell-mediate immunity	Form multi-nucleated myotubes, yielding protein markers for myocytes[9]
Energetic balance	N2 supplement	Chemically defined formulation containing insulin, transferrin, progesterone, putrescine and selenite	In vitro survival and expression of post-mitotic neurons in primary cultures from both the peripheral nervous system and the central nervous system	General promotion of neural cell survival
	B27 supplement	Mixture of vitamins (biotin, Tocopherol, Vitamin A), proteins (BSA, catalase, insulin transferrin, superoxide dismutase), Corticosterone, Galactose, Ethanolamine, Glutathione, Carnitine, Linoleic acid, linolenic acid, progesterone, putrescine, selenite, T3	Growth and maintenance of neurons. Differentiating Glial Precursor Cells into Astrocytes and Oligodendrocytes. Differentiating Neural Stem Cells into Neurons and Glial Cells

ASCs: Adipose stem cells.