Abstract
Stem cells are highly important in biology due to their unique innate ability to self-renew and differentiate into other specialised cells. In a neurological context, treating major injuries such as traumatic brain injury, spinal cord injury and stroke is a strong basis for research in this area. Mesenchymal stem cells (MSC) are a strong candidate because of their accessibility, compatibility if autologous, high yield and multipotency with a potential to generate neural cells. With the use of small-molecule chemicals, the neural induction of stem cells may occur within minutes or hours. Isobutylmethyl xanthine (IBMX) has been widely used in cocktails to induce neural differentiation. However, the key molecular mechanisms it instigates in the process are largely unknown. In this study we showed that IBMX-treated mesenchymal stem cells induced differentiation within 24 h with the unique expression of several key proteins such as Adapter protein crk, hypoxanthine-guanine phosphoribosyltransferase, DNA topoisomerase 2-beta and Cell division protein kinase 5 (CDK5), vital in linking signalling pathways. Furthermore, the increased expression of basic fibroblast growth factor in treated cells promotes phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) cascades and GTPase–Hras interactions. Bioinformatic and pathway analyses revealed upregulation in expression and an increase in the number of proteins with biological ontologies related to neural development and substructure formation. These findings enhance the understanding of the utility of IBMX in MSC neural differentiation and its involvement in neurite substructure development.
Highlights
Stem cells are highly important in biology due to their unique innate ability to self-renew and differentiate into other specialised cells
The aim of this study is to investigate the effect of Isobutylmethyl xanthine (IBMX) treatment in Mesenchymal stem cells (MSC) differentiation to a neural-like lineage through phenotypic, proteomic and cytokine expression changes expounding on the molecular mechanisms involved
The chemical treatment of MSCs with IBMX was performed with the intent to observe phenotypic and morphological features congruent with neural cell types
Summary
Stem cells are highly important in biology due to their unique innate ability to self-renew and differentiate into other specialised cells. Their potential in medical applications is rapidly growing in the areas of cellular and tissue repair and regeneration, and they have the potential to treat and understand diseases. Regenerative cellular treatments for major injuries are a strong basis for research in this area. These include traumatic brain injury (TBI) [7], spinal cord injury [8], and stroke [9]. Neural tissue alone has a limited capacity to regenerate [10], but stem cells have the broad potential to regenerate lost or impaired tissue function from injury [11]
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