Skin derived precursors induced Schwann cells mediated tissue engineering-aided neuroregeneration across sciatic nerve defect

A central question in neural tissue engineering is how the tissue-engineered nerve(TEN)translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes.Here,we report a skin-derived precursor-induced Schwann cell(SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft(SKP-SCs-TEN)that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral,histological,and electrophysiological evidence.For achieving better effect of neuroregeneration,this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix(ECM).To overcome the limitation of traditional tissue-engineered nerve grafts,jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration.To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration,we performed a cDNA microarray analysis of gene expression profiling,a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues.A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration.Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.

Application of stem cells in peripheral nerve regeneration

Traumatic peripheral nerve injury is a worldwide clinical issue with high morbidity.The severity of peripheral nerve injury can be classified as neurapraxia,axonotmesis or neurotmesis,according to Seddon’s classification,or five different degrees according to Sunderland’s classification.Patients with neurotmesis suffer from a complete transection of peripheral nerve stumps and are often in need of surgical repair of nerve defects.The applications of autologous nerve grafts as the golden standard for peripheral nerve transplantation meet some difficulties,including donor nerve sacrifice and nerve mismatch.Attempts have been made to construct tissue-engineered nerve grafts as supplements or even substitutes for autologous nerve grafts to bridge peripheral nerve defects.The incorporation of stem cells as seed cells into the biomaterial-based scaffolds increases the effectiveness of tissue-engineered nerve grafts and largely boosts the regenerative process.Numerous stem cells,including embryonic stem cells,neural stem cells,bone marrow mesenchymal stem cells,adipose stem cells,skin-derived precursor stem cells and induced pluripotent stem cells,have been used in neural tissue engineering.In the current review,recent trials of stem cell-based tissue-engineered nerve grafts have been summarized;potential concerns and perspectives of stem cell therapeutics have also been contemplated.