Copyright ©The Author(s) 2018.
World J Stem Cells. Mar 26, 2018; 10(3): 23-33
Published online Mar 26, 2018. doi: 10.4252/wjsc.v10.i3.23
Table 1 Functions of growth factors on neural induction of adipose stem cells
Growth factorsProfilePhysiological activityEffect on ASCsRemarks
EGFSmall polypeptide of 53 amino acid residues and a molecular mass of approximately 6000 daltons[57]Development of the oral cavity, lungs, gastrointestinal tract, epidermis, derma, eyelids and central nervous system[56]Promotion of proliferation with delays of senescence and insurance of differentiation potency[55]EGF and bFGF co-administration limits ASCs differentiation abilities by inducing ASCs into an ectodermal lineage rather than the mesodermal one[53]
bFGFNon-glycosylated polypeptide of 18 kDa and 155 amino acid in length (heparin-binding growth factor family)Stimulator of tissue repair and cellular viability released from an injured extracellular matrix[64]Enhancement of proliferation, differentiation and hepatocyte growth factor expression ability[58]. Induction of the adipogenic[59] and chondrogenic[60] potential, with inhibition of osteogenic differentiation[61]
PDGFDimeric glycoproteinPotent mitogen for cell of mesodermal lineage and stimulator of tissue repair released from activated platelets on bleeding[65]Supporting of cell proliferation in vitro: It increases ASCs yield. Promotion of neural differentiation in an antioxidant microenvironment[48]Receptor-β signalling is involved primarily in ASCs stimulation[62]. ASCs stimulation with autologous platelet-rich plasma reduces the cost of differentiation[48]
Table 2 Effects of chemicals-enriched microenvironment on adipose stem cells fate
ActionChemicals/drugsProfileRecognized functionEffects on ASCs
Antioxidantβ-mercaptoethanolWater-soluble thiol used as a reducing agent for disulfide bonds to protect sulfhydryl groups from oxidationIn 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 hydroxyanisoleMixture of two isomeric organic compoundsInhibition of 17 β-estradiol(E2)-mediated oxidative stress and of oxidative DNA damage
N-acetyl-l-cysteineSynthetic derivative of endogenous amino acid, L-cysteine, precursor of the antioxidant enzyme GlutathioneStimulator of glutathione synthase Activator of NMDA1 receptorWhen 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 vitaminReducing agent and coenzyme in several metabolic pathways
Interference on DNAValproic acidBranch-chained fatty acid, acting as a histone deacetylase inhibitorWide 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-azacytidineAnalog 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-inflammationIndomethacinSynthetic nonsteroidal indole derivativeInhibitor of COX1/2Component of neural induction medium applied for two weeks[44]
Immuno modulationHydrocortisoneGlucocorticoid hormoneSuppressor of cell-mediate immunityForm multi-nucleated myotubes, yielding protein markers for myocytes[9]
Energetic balanceN2 supplementChemically defined formulation containing insulin, transferrin, progesterone, putrescine and seleniteIn vitro survival and expression of post-mitotic neurons in primary cultures from both the peripheral nervous system and the central nervous systemGeneral promotion of neural cell survival
B27 supplementMixture 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, T3Growth and maintenance of neurons. Differentiating Glial Precursor Cells into Astrocytes and Oligodendrocytes. Differentiating Neural Stem Cells into Neurons and Glial Cells
Table 3 Biomaterials for neural phenotype of adipose stem cells
BiomaterialsProfileEffect on ASCsTest on animalLimitation for clinical
Chitosan filmsNaturally derived polysaccharide from chitin[81,82]Spontaneous cell organization in a 3D architectureYes, higher cellular retention ratio of ASC spheroids after intramuscular injection in nude mouse[81]Not declared
Chitosan and gelatinElastic-dominant, porous scaffoldConditioning toward a neuron-like phenotypeYes, better repair in a mouse model of traumatic brain injury[83]Not declared
Chitosan and silkComplex structural frameworkEfficient as delivery vehicle for ASCsYes, proposed as nerve grafts in the regeneration of injured rat sciatic nerve[84]Not declared
Collagen gelEngineered neural tissueCells must be aligned to collagen fibresYes, supported robust neural regeneration of injured rat sciatic nerve[85]Not declared
AlbuminSerum-derived porous scaffoldPromotion toward neuronsYes, filler effect on the spinal cord cavity in animal models of spinal cord injury[86]Not declared
MatrigelCommercially available hydrogelGood cell encapsulation and delivery[87]Yes, mouse models of spinal cord injuryNot applicable for its isolation from the basement membrane of a mouse sarcoma
AlginateHydrogelNeurospheres encapsulation and neural promotion[88,89]Good biocompatible profile
Nanosized graphene oxide-laminin hybrid patternsEngineered tissueEfficient neuron-like cells differentiation[90]