The Effects of Epidermal Neural Crest Stem Cells on Local Inflammation Microenvironment in the Defected Sciatic Nerve of Rats

Abstract

Cell-based therapy is a promising strategy for the repair of peripheral nerve injuries (PNIs). epidermal neural crest stems cells (EPI-NCSCs) are thought to be important donor cells for repairing PNI in different animal models. Following PNI, inflammatory response is important to regulate the repair process. However, the effects of EPI-NCSCs on regulation of local inflammation microenviroment have not been investigated extensively. In the present study, these effects were studied by using 10 mm defected sciatic nerve, which was bridged with 15 mm artificial nerve composed of EPI-NCSCs, extracellular matrix (ECM) and poly (lactide-co-glycolide) (PLGA). Then the expression of pro- and anti-inflammatory cytokines, polarization of macrophages, regulation of fibroblasts and shwann cells (SCs) were assessed by western blot, immunohistochemistry, immunofluorescence staining at 1, 3, 7 and 21 days after bridging. The structure and the function of the bridged nerve were determined by observation under light microscope and by examination of right lateral foot retraction time (LFRT), sciatic function index (SFI), gastrocnemius wet weight and electrophysiology at 9 weeks. After bridging with EPI-NCSCs, the expression of anti-inflammatory cytokines (IL-4 and IL-13) was increased, but decreased for pro-inflammatory cytokines (IL-6 and TNF-α) compared to the control bridging, which was consistent with increase of M2 macrophages and decrease of M1 macrophages at 7 days after transplantation. Likewise, myelin-formed SCs were significantly increased, but decreased for the activated fibroblasts in their number at 21 days. The recovery of structure and function of nerve bridged with EPI-NCSCs was significantly superior to that of DMEM. These results indicated that EPI-NCSCs could be able to regulate and provide more suitable inflammation microenvironment for the repair of defected sciatic nerve.

BMP4 knockdown of NCSCs leads to aganglionosis in the middle embryonic stage

“…However, at present, there is a lack of a genetic mouse models that exhibits HD gene knockdown with unmistakeable implementation. NCSCs originate from cells of the neural crest that migrate in chains as they colonize the embryonic gut, eventually forming the myenteric and submucosal plexus (27)(28)(29). Failure of the neural crest cells to colonize the gut leads to aganglionosis in the sigmoid colon, a pathological condition called Hirschsprung's disease, also known as congenital megacolon, in humans (28,29).…”

“…NCSCs originate from cells of the neural crest that migrate in chains as they colonize the embryonic gut, eventually forming the myenteric and submucosal plexus (27)(28)(29). Failure of the neural crest cells to colonize the gut leads to aganglionosis in the sigmoid colon, a pathological condition called Hirschsprung's disease, also known as congenital megacolon, in humans (28,29). At present, the mechanism associated withthe signalling pathways that adjust NCSCs for migration to the intestinal tract and differentiation in the enteric nervous system remains unclear.…”

Prospects of neural crest‐derived cells from oral and dentofacial tissues for application in regenerative medicine

“…In mouse models of spinal cord injury, grafted murine epidermal NCDCs were found to integrate with surrounding host spinal tissue 65 . Epidermal NCDCs were also shown to be function as donor cells for repairing peripheral nerve injury in an animal model 66 . In a study of hard tissue regeneration, a mixture of skin‐derived NCDCs and hydroxyapatite/tricalcium phosphate was transplanted into rat calvarial defects, and the NCDCs were found to differentiate into osteogenic structures 67 .…”

Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture

“…Also, EPI‐NCSCs are ontologically related to nervous system stem cells and express both neuronal and glial markers (Pandamooz, Naji, Alinezhad, Zarghami, & Pourghasem, ). As the nervous system is a familiar context for EPI‐NCSCs, numerous studies are using these stem cells in animal models of spinal cord injury (Hu et al, ; Y. Li et al, ; Lu, Li, Liu, & Dong, ; Pandamooz et al, ). Although EPI‐NCSCs has considerable advantages over other stem cells, little is known about their biomechanical interactions with their microenvironment.…”