Using Epidermal Neural Crest Stem Cells in Experimental Models of Spinal Cord Injury

Spinal cord injury (SCI) and its attendant neurodegenerativeprocesses is a serious health issue in which the current surgicaland pharmacological management approaches fail to fully overcomethe devastating condition. A search through experimentaland undergoing clinical trials reveal that cell-based therapiesusing a variety of embryonic stem cells, adult mesenchymalstem cells and induced pluripotent stem cells are active fields ofresearch in SCI treatment. The mechanisms through which thecells may repair the injured spinal cord are immunomodulation,providing a trophic support and/or replacing the injured neuronsand glia to restore the architecture and function. However, theseattempts have not yet been sufficiently successful to achieve theregulatory approval as standard and popular treatment goals.Although this failure may partly reflect the neglecting complexneuropathology of SCI which necessitates multi-target therapeuticapproaches, can be also attributed to the source of stemcells making not adequate therapeutic concent or accompanyingadverse reactions. Therefore, searching for more appropriatesources of stem cells and combining the cell-based therapieswith other approaches to manipulate the inhospitable contextof injured tissue and strength the cells are of great importance.Epidermal neural crest stem cells (EPI-NCSCs) are multipotentadult stem cells that originate from the dorsal developing neuraltube, reside in the bulge of hair follicles and persist postnatallyinto adult life. These cells were first introduced by Sieber-Blumet al., in ۲۰۰۴, isolated form bulge explants of adult mousewhisker follicles. Thereafter, EPI-NCSCs were also isolatedand characterized from rat, canine and human. In addition tohigh degree of innate plasticity of EPI-NCSCs, the migratorybehavior of these cells which yields a high pure population ofstem cells, and their accessibility through minimal invasiveprocedures have all established them as potential candidate inautologous cell-based therapies.Using ex vivo (organotypic slice culture) and in vivo models oftraumatic SCI, we currently evaluate the efficacy of rat EPINCSCscombined with pharmacological agents. The drugs areselected based on potential effects on the survival, proliferationand differentiation of isolated stem cells and in parallel modulatingthe host tissue. Based on our results, valproic acid, awidely used antiepileptic drug, which acts as a histone deacetylaseinhibitor and fingolimod, an immunomodulating drug fortreating multiple sclerosis, which acts as a sphingosine ۱-phosphatereceptor modulator are introduced as promising candidatesfor EPI-NCSC combinatorial treatments of SCI.

کلیدواژه ها:

Epidermal Neural Crest Stem Cells ، Spinal Cord Injury ، Valproic Acid ، Fingolimod