A Nerve Conduit Containing a Vascular Bundle and Implanted with Bone Marrow Stromal Cells and Decellularized Allogenic Nerve Matrix

Abstract

Cells, scaffolds, growth factors, and vascularity are essential for nerve regeneration. Previously, we reported that the insertion of a vascular bundle and the implantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into a nerve conduit promoted peripheral nerve regeneration. In this study, the efficacy of nerve conduits containing a vascular bundle, BM-MSCs, and thermally decellularized allogenic nerve matrix (DANM) was investigated using a rat sciatic nerve model with a 20-mm defect. Lewis rats were used as the sciatic nerve model and for the preparation of BM-MSCs, and Dark Agouti rats were used for the preparation of the DANM. The revascularization and the immunogenicity of the DANM were investigated histologically. The regeneration of nerves through nerve conduits containing vessels, BM-MSCs, and DANM (VBD group) was evaluated based on electrophysiological, morphometric, and reinnervated muscle weight measurements and compared with that of vessel-containing conduits that were implanted with BM-MSCs (VB group). The DANM that was implanted into vessel-containing tubes (VCTs) was revascularized by neovascular vessels that originated from the inserted vascular bundle 5-7 days after surgery. The number of CD8 + cells found in the DANM in the VCT was significantly smaller than that detected in the untreated allogenic nerve segment. The regenerated nerve in the VBD group was significantly superior to that in the VB group with regard to the amplitude of the compound muscle action potential detected in the pedal adductor muscle; the number, diameter, and myelin thickness of the myelinated axons; and the tibialis anterior muscle weight at 12 and 24 weeks. The additional implantation of the DANM into the BM-MSC-implanted VCT optimized the axonal regeneration through the conduit. Nerve conduits constructed with vascularity, cells, and scaffolds could be an effective strategy for the treatment of peripheral nerve injuries with significant segmental defects.

A scaffold‐free Bio 3D nerve conduit for repair of a 10‐mm peripheral nerve defect in the rats

“…Fifth, the size mismatch between the diameter of the conduit and the sciatic nerve should be discussed. We decided to use the diameter of the bio 3D conduit from previous studies, which was larger than that of the sciatic nerve (Kaizawa et al, ; Yurie et al, ). However, a narrower conduit was used in other studies (Kim, Lee, Jeon, et al, ; Mohammadi, Shokrzadeh, & Maroufi, ).…”

“…In tissue engineering, cells, scaffolds, and growth factors are considered to be essential elements for promoting regeneration (Kaizawa, Kakinoki, Ikeguchi, et al, 2016;Widgerow, Salibian, Kohan, et al, 2014). Several researchers have reported that administration of stem cells or biologically active molecules into artificial scaffolds enhances the regenerative potential (Eren et al, 2016;Kaizawa et al, 2016;Kaizawa, Kakinoki, Ikeguchi, et al, 2017). However, when using artificial scaffolds, problems related to biocompatibility induced by a foreign body reaction are inherent risks.…”

Development of Nerve Conduit using Decellularized Human Umbilical Cord Artery Seeded with Centella asiatica Induced-Neurodiferrentiated Human Mesenchymal Stem Cell

“…An ideal nerve conduit should support recellularization because the seeding of the cells into nerve conduit has been shown to be essential in promoting nerve regeneration (Kaizawa et al 2017(Kaizawa et al , 2016Shalaby et al 2017;Xu et al 2016). To test whether decellularized HUC artery conduit support recellularization, mesenchymal stem cells and neurodifferentiated mesenchymal stem cells (ndMSCs) were seeded into the luminal surface of the decellularized HUC artery and incubated for 2 days.…”

“…It was estimated that 50000 procedures were performed annually to repair damaged peripheral nerves at the cost of USD 7 billion per year (Liao et al 2013). Despite rapid clinical advancement, the treatment of PNI is still a challenge especially in critical gap (greater than 3 cm) (Kaizawa et al 2017;Liao et al 2013). This condition is worsened by the limited regeneration of peripheral nerve that depends on several factors including the length of injury, presence of neurotrophic factors and Schwann cells (Höke 2006).…”

A basic fibroblast growth factor slow‐release system combined to a biodegradable nerve conduit improves endothelial cell and Schwann cell proliferation: A preliminary study in a rat model

“…Currently, there is a growing interest in the clinical potential of mesenchymal stem cells derived from bone marrow (Kaizawa et al, 2017), adipose tissue (Kappos et al, 2015;Saller et al, 2018), and menstrual blood (Farzamfar et al, 2017). Among these, bone marrow stem cells are reported to enhance neovascularization by producing angiopoietin-1 and 2 (Yang, Cai, Xu, Xu, & Liang, 2015).…”