Tissue-Engineered Regeneration of Completely Transected Spinal Cord Using Induced Neural Stem Cells and Gelatin-Electrospun Poly (Lactide-Co-Glycolide)/Polyethylene Glycol Scaffolds

Abstract

Tissue engineering has brought new possibilities for the treatment of spinal cord injury. Two important components for tissue engineering of the spinal cord include a suitable cell source and scaffold. In our study, we investigated induced mouse embryonic fibroblasts (MEFs) directly reprogrammed into neural stem cells (iNSCs), as a cell source. Three-dimensional (3D) electrospun poly (lactide-co-glycolide)/polyethylene glycol (PLGA-PEG) nanofiber scaffolds were used for iNSCs adhesion and growth. Cell growth, survival and proliferation on the scaffolds were investigated. Scanning electron microcopy (SEM) and nuclei staining were used to assess cell growth on the scaffolds. Scaffolds with iNSCs were then transplanted into transected rat spinal cords. Two or 8 weeks following transplantation, immunofluorescence was performed to determine iNSC survival and differentiation within the scaffolds. Functional recovery was assessed using the Basso, Beattie, Bresnahan (BBB) Scale. Results indicated that iNSCs showed similar morphological features with wild-type neural stem cells (wt-NSCs), and expressed a variety of neural stem cell marker genes. Furthermore, iNSCs were shown to survive, with the ability to self-renew and undergo neural differentiation into neurons and glial cells within the 3D scaffolds in vivo. The iNSC-seeded scaffolds restored the continuity of the spinal cord and reduced cavity formation. Additionally, iNSC-seeded scaffolds contributed to functional recovery of the spinal cord. Therefore, PLGA-PEG scaffolds seeded with iNSCs may serve as promising supporting transplants for repairing spinal cord injury (SCI).

Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo

“…As one of the few biomaterials approved by the United States Food and Drug Administration (FDA) and European Medicine Agency (EMA) for experimental and clinical application, PLGA has broad utility in drug delivery, artificial catheter and tissue engineering67. Due to the easy controlling of mechanical properties and biodegradation, PLGA is one of the top biodegradable synthetic polymers used for tissue engineering, especially neural tissue engineering8. It has been used as carrier for various cells to restore injured nerve910.…”

PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury

“…A number of studies focused on the capability of biomaterial scaffolds seeded with differentiated stem cells to treat SCI (Agbay et al, ; Libro et al, ; Liu et al, ; Shrestha et al, ; Tabesh et al, ; Xia et al, ; Yang et al, ), and here we present a novel combination of PCL/gelatin scaffolds seeded with hEnSCs that have been differentiated by coculturing with hSCs to treat SCI in rats. This study is significant for two reasons.…”

Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats

“…Most importantly, owing to their well-controlled degradation rate, low toxicity as well as immunogenicity [8], PLGA complexes seem to be an expedient complex for the adherence and growth of inoculating cells. Similarly, a number of studies have postulated OECs to be a suitable choice for the treatment and replacement of injured spinal cord by virtue of their multi-lineage differentiation potential coupled to a unique self-renewal ability [23, 44, 45].…”

“…There have been several investigations into engineered bio-constructs that use various types of cell-seeded bio-complexes [5-7], the two integral parts being an appropriate cell source and a suitable complex [8]. A number of previous studies have shown that transplantation of neural stem cells like embryonic stem cells [9], mesenchymal stem cells [10] and glial cells, such as schwann cells [11], bone marrow stromal cells [12]or olfactory ensheathing cells [13] into the lesion site of the SCI can significantly promote axonal regeneration and functional recovery.…”