Comparison of the Efficiencies of Three Neural Induction Protocols in Human Adipose Stromal Cells

Abstract

The aim of this study was to compare the neural differentiation potential and the expression of neurotrophic factors (NTFs) in differentiated adipose-derived stem cells (ADSCs) using three established induction protocols, serum free (Protocol 1), chemical reagents (Protocol 2), and spontaneous (Protocol 3) protocols. Protocol 1 produced the highest percentage of mature neural-like cells (MAP2ab(+)). Protocol 2 showed the highest percentage of immature neural-like cells (beta-tubulin III(+)), but the neural-like state was transient and reversible. Protocol 3 caused ADSCs to differentiate spontaneously into immature neural-like cells, but not into mature neural cell types. The neural-like cells produced by Protocol 1 lived the longest in culture with little cell death, but Protocol 2 and 3 led to the significant cell death. Therefore, Protocol 1 is the most efficient among these protocols. Additionally, soon after differentiation, the mRNA levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in dADSCs were sharply decreased by Protocol 1 and 2 (acute induction protocol), but not by Protocol 3 (chronic induction protocol). The results indicate that NTFs played an important role in neural differentiation via acute responses to NGF and BDNF, but not chronically during the transdifferentiation process.

Adipose-Derived Stem Cells Promote Peripheral Nerve Regeneration In Vivo without Differentiation into Schwann-Like Lineage

“…7 Several groups revealed that adipose-derived stem cells have as high a potential to support regeneration of peripheral nerve tissue in vitro as do Schwann cells. [8][9][10][11][12] We previously showed that adipose-derived stem cells produced various soluble factors that promoted peripheral nerve regeneration in vitro. 13 However, there have been few reports that compared the ability of adipose-derived stem cells and Schwann cells to repair peripheral nerve injury in animal models.…”

Comparative study of neural differentiation of bone marrow mesenchymal stem cells by different induction methods

“…Reports indicate that the neural differentiation of MSCs is achieved by using different experimental protocols, Protocols include using chemical agents like β-mercaptoethanol, tretinoin, a mix of DMSO and butylatedhydroxyanisole, or a mix of IBMX and indomethacin (Fu et al, 2008;Qian et al, 2010;Tse et al, 2010;Kaka et al, 2012). We then compared the effectiveness and the safety of these induction methods.…”

Transplantation of Adipose-Derived Stem Cells in Stroke

“…Despite the relatively small number of ADSC to explain the overall functional recovery in the reported studies, their presence signifies "transdifferentitation" as a possible mechanism underlying the positive therapeutic impact (Gutierrez-Fernandez et al 2013a). Indeed, the capacity of neural differentiation for ADSC has been extensively investigated (Cardozo et al 2010;Kompisch et al 2010;Liao et al 2010;Qian et al 2010;Abdanipour et al 2011;Yu et al 2011;Ahmadi et al 2012). It has also been reported that, compared with bone marrow-derived mesenchymal stem cells, ADSC have superior neurogenic potential (Kang et al 2004).…”

“…A study investigating the fate of human ADSC from different human donors after being subcutaneously injected into immunodeficient SCID mice showed that the cells survived for at least 17 months with subsequent differentiation into fibroblasts of the subdermic connective tissue and into mature adipocytes of fat tissue, exclusively at the site of injection without evidence of migration or fusion with host cells (Lopez-Iglesias et al 2011), underscoring the safety of ADSC transplantation. Moreover, the use of terminally differentiated ADSC may be a possible option for minimizing the risk especially when the protocols for in vitro transdifferentiation of ADSC into neuronal lineage have been well-documented (Cardozo et al 2010;Kompisch et al 2010;Liao et al 2010;Qian et al 2010;Abdanipour et al 2011;Yu et al 2011;Ahmadi et al 2012). Indeed, the use of induced ADSC has been endorsed as a promising therapeutic option in stroke treatment (Yang et al 2011;Shen et al 2013).…”