Repair of Rat Sciatic Nerve Defects by Using Allogeneic Bone Marrow Mononuclear Cells Combined with Chitosan/Silk Fibroin Scaffold

Abstract

The therapeutic benefits of bone marrow mononuclear cells (BM-MNCs) in many diseases have been well established. To advance BM-MNC-based cell therapy into the clinic for peripheral nerve repair, in this study we developed a new design of tissue-engineered nerve grafts (TENGs), which consist of a chitosan/fibroin-based nerve scaffold and BM-MNCs serving as support cells. These TENGs were used for interpositional nerve grafting to bridge a 10-mm-long sciatic nerve defect in rats. Histological and functional assessments after nerve grafting showed that regenerative outcomes achieved by our developed TENGs were better than those achieved by chitosan/silk fibroin scaffolds and were close to those achieved by autologous nerve grafts. In addition, we used green fluorescent protein-labeled BM-MNCs to track the cell location within the chitosan/fibroin-based nerve scaffold and trace the cell fate at an early stage of sciatic nerve regeneration. The result suggested that BM-MNCs could survive at least 2 weeks after nerve grafting, thus helping to gain a preliminary mechanistic insight into the favorable effects of BM-MNCs on axonal regrowth.

Relevance and Recent Developments of Chitosan in Peripheral Nerve Surgery

“…The results led to a nearly similar degree of functional regeneration compared to the ANT (Ding et al, 2010; Xue et al, 2012). Interestingly, Yao et al (2016) was able to show, that Bone Marrow Mononuclear Cells joined with a chitosan/silk fibroin scaffold survived at least 2 weeks under in vivo conditions associated with an improved axonal guidance. Nearly similar results for functional recovery was accomplished compared to the ANT in the CatWalk gait analysis after 12 weeks of recovery (Yao et al, 2016).…”

“…Interestingly, Yao et al (2016) was able to show, that Bone Marrow Mononuclear Cells joined with a chitosan/silk fibroin scaffold survived at least 2 weeks under in vivo conditions associated with an improved axonal guidance. Nearly similar results for functional recovery was accomplished compared to the ANT in the CatWalk gait analysis after 12 weeks of recovery (Yao et al, 2016). However, SC harvested during nerve surgery need long cultivation times to reach sufficient cell numbers for reimplantation and are associated with a loss of function related to donor’s nerve.…”

Bone marrow-derived neural crest precursors improve nerve defect repair partially through secreted trophic factors

“…Therefore several stem cells and their derivatives are notable in the replacement of Schwann cells seeded in conduits to create tissue-engineered nerve grafts (TENG), which is considered as a promising alternative to autograft nerve transplant [11]. Mesenchymal stem cells (MSCs) have been supplemented into silk fibroin fiber scaffolds/chitosan conduits to construct TENG for bridging nerve gap in rats, dogs, and rhesus monkeys [12–15]. More recently, SCPs produced from human-induced pluripotent stem cells (iPSCs) were reported as a potential therapeutic target for myelin repair in mice [16].…”

Study of transected sciatic nerve repair by biodegradable membrane and betamethasone in adult albino wistar rats

“…In this study, SFI oscillates around 0 for normal nerve function, and around 100 SFI for transected nerve function which represents total motor sciatic nerve dysfunction (37).…”