In vitro transdifferentiation of human adipose tissue-derived stem cells to neural lineage cells - a stage-specific incidence

Abstract

The present Study investigated the intrinsic ability of adipose tissue-derived stem cells (ADSCs) and their neural transdifferentiation in a stage-specific manner. Woodbury’s Chemical induction was implemented with modifications to achieve neural transdifferentiation. In Group I, ADSCs were preinduced with β-mercaptoethanol (β-ME) and later, with neural induction medium (NIM). In Group II, ADSCs were directly treated with NIM. In Group III, a DNA methyltransferase (DNMT) inhibitor 5-azacytidine was applied to understand whether transdifferentiation is controlled by epigenetic marks. Irrespective of the presence of (β-ME), the differentiation protocol resulted in glial-lineage cells. Group III produced poorly -differentiated neural cells with neuron-specific enolase positivity. A neuroprogenitor stage (NPC) was identified at d 11 after induction only in Group I. In other groups, this stage was not morphologically distinct. We explored the stage-specific incidence NPC, by alternatively treating them with basic fibroblast growth factor (bFGF), and antioxidants to validate if different signalling could cause varied outcomes (Group IV). They differentiated into neurons, as defined by cell polarity and expression of specific proteins. Meanwhile, neuroprogenitors exposed to NIM (Group I) produced glial-lineage cells. Further refinement and study of the occurrence and terminal differentiation of neuroprogenitors would identify a promising source for neural tissue replacement.

Lack of a skeletal muscle phenotype in adult human bone marrow stromal cells following xenogeneic-free expansion

“…Our study showed that bmMSCs conditioned with P/PL also showed cytoplasmic GAP-43 expression, as opposed to the human myoblast SJCRH30 cell line which showed nuclear staining. This cytoplasmic expression is in line with other MSC studies that used bFGF or epidermal growth factor (EGF) to differentiate bmMSCs into functional neuronal cells expressing GAP-43 [90][91][92][93]. PL has been shown to contain high amounts of both bFGF and EGF, in addition to a number of other growth factors [39][40][41][42].…”

Phenotypical Characterization and Neurogenic Differentiation of Rabbit Adipose Tissue-Derived Mesenchymal Stem Cells

“…In addition to basic three lineage differentiation, AT-MSCs have been shown to have neurogenic differentiation potential [ 66 ] and can also differentiate into cardiomyocytes and myocytes [ 67 ], endothelial cells [ 68 ] or hepatocytes [ 69 ]. The capability of AT-MSCs to differentiate into neuro-lineage possesses an outstanding potential for treating various neurological disorders.…”

Differentiation of human adult-derived stem cells towards a neural lineage involves a dedifferentiation event prior to differentiation to neural phenotypes

“…Literature published over the past 20 years have shown that mesenchymal stem cells (MSCs) isolated from adult tissues can be induced to overcome their mesenchymal fate and transdifferentiate into neural cells 11 – 18 . Although the transdifferentiation of human MSCs into neurons has aroused considerable interest, as it would have immense clinical potential in cell replacement therapy and regenerative medicine 19 , 20 , the findings and their interpretation have been challenged 21 , 22 .…”