Epidermal neural crest stem cell transplantation as a promising therapeutic strategy for ischemic stroke

Abstract

IntroductionCell‐based therapy is considered as promising strategy to cure stroke. However, employing appropriate type of stem cell to fulfill many therapeutic needs of cerebral ischemia is still challenging. In this regard, the current study was designed to elucidate therapeutic potential of epidermal neural crest stem cells (EPI‐NCSCs) compared to bone marrow mesenchymal stem cells (BM‐MSCs) in rat model of ischemic stroke.MethodsIschemic stroke was induced by middle cerebral artery occlusion (MCAO) for 45 minutes. Immediately after reperfusion, EPI‐NCSCs or BM‐MSCs were transplanted via intra‐arterial or intravenous route. A test for neurological function was performed before ischemia and 1, 3, and 7 days after MCAO. Also, infarct volume ratio and relative expression of 15 selected target genes were evaluated 7 days after transplantation.ResultsEPI‐NCSCs transplantation (both intra‐arterial and intravenous) and BM‐MSCs transplantation (only intra‐arterial) tended to result in a better functional outcome, compared to the MCAO group; however, this difference was not statistically significant. The infarct volume ratio significantly decreased in NCSC‐intra‐arterial, NCSC‐intravenous and MSC‐intra‐arterial groups compared to the control. EPI‐NCSCs interventions led to higher expression levels of Bdnf, nestin, Sox10, doublecortin, β‐III tubulin, Gfap, and interleukin‐6, whereas neurotrophin‐3 and interleukin‐10 were decreased. On the other hand, BM‐MSCs therapy resulted in upregulation of Gdnf, β‐III tubulin, and Gfap and down‐regulation of neurotrophin‐3, interleukin‐1, and interleukin‐10.ConclusionThese findings highlight the therapeutic effects of EPI‐NCSCs transplantation, probably through simultaneous induction of neuronal and glial formation, as well as Bdnf over‐expression in a rat model of ischemic stroke.

The Beneficial Potential of Genetically Modified Stem Cells in the Treatment of Stroke: A Review

“…This striking data supports the beneficial function of these grafted stem cells in damaged tissues. Furthermore, EPI-NCSCs showed superior immunomodulation properties in animal models of nerve injury and stroke, as they upregulated the anti-inflammatory cytokines, whilst reducing the expression of pro-inflammatory cytokines [34,124,125]. Since EPI-NCSCs can easily be transduced to overexpress GFP [126], genetic manipulations to elevate neurotrophic factor expression seems feasible, and with this review we hope to prompt further studies investigating the beneficial characteristics of those cells.…”

“…Based on the above presented studies, BM-MSCs and neural stem cells are the most abundantly used cell-types that can be genetically modified to enhance their potential when transplanted in animal models of stroke. However, our investigations revealed that epidermal neural crest stem cells (EPI-NCSCs) can also benefit the inhospitable context of rat model of ischemic stroke [34] as well as ex vivo [114] and in vivo [115] models of spinal cord injury. EPI-NCSCs are located in the bulge area of the hair follicle, and retain the differentiation potential of their neural crest origin, so that they can differentiate into neural lineages [116].…”

“…According to accumulating evidence, EPI-NCSCs express several trophic factors, which their rate of expression can be manipulated through the use of different chemical agents [119][120][121][122] to achieve optimum efficiency after transplantation. In addition, administration of EPI-NCSCs via intra-arterial or intra venous routes following reperfusion, created a comparable outcome to intra-arterial grafted BM-MSCs, 7 days after cerebral ischemia [34]. It has been implicated that grafted EPI-NCSCs are mostly acting through the secretion of various trophic factors such as BDNF, GDNF, NT3, NGF and VEGF that can impose different modulatory functions [123].…”

“…Furthermore, their effectiveness and mechanisms of action have been thoroughly reviewed during the last few years. Moreover, other types of stem cells, such as bone marrow mononuclear cells [24,25], induced pluripotent stem cells [26][27][28][29], dental pulp stem cells [30,31], menstrual bloodderived stem cells [32,33] and epidermal neural crest stem cells [34] have been evaluated. Releasing growth factors by stem cells is considered as one of the most important therapeutic aspects of cell-based therapy [35].…”

Epidermal Neural Crest Stem Cells as a Perspective for COVID-19 Treatment

“…In cerebral ischemia, EPI-NCSCs and BM-MSCs show equal therapeutic potential [ 7 ]. In animal models of peripheral nerve injury [ 8 ] and stroke [ 7 ], EPI-NCSCs showed superior immunomodulation properties. Furthermore, EPI-NCSCs demonstrated their curative abilities in Alzheimer’s disease, and in vivo as well as ex vivo models of spinal cord injury.…”