Nerve Regeneration Promoted in a Tube with Vascularity Containing Bone Marrow-Derived Cells

Abstract

Bone marrow-derived cells (BMCs) are multipotent cells that have the potential to differentiate into bone, cartilage, fat, muscle, or neuronal lineages such as neurons and glial cells. A silicone tube model containing reverse-pedicled sural vessels was created in the sciatic nerves of Lewis rats. About 1 × 10 7 BMCs, removed from the bone marrow of synergetic rat femurs and cultured in vitro, were transplanted into the 15-mm-long chambers of the silicone tubes. Nerve regeneration in vessel-containing tubes that had received BMCs was significantly greater at 12 and 24 weeks after surgery than in tubes that did not receive cells. Transplantation of fibroblasts instead of BMCs into the vessel-containing tube resulted in reduced axonal regeneration, which was inferior to regeneration in the vessel-containing tube that did not receive cells. Polymerase chain reaction (PCR) studies revealed that in vessel-containing tubes containing transplanted BMCs, about 29% of cells in the regenerated nerve originated from BMCs. Cells identified by in situ hybridization and PKH26 prelabeling as being of BMC origin stained positively for S100 and GFAP. Transplanted BMCs differentiated into cells with phenotypes similar to those of Schwann cells under the influence of neurochemical factors and survived by obtaining nutrients from vessels that had been preinserted into the tube. They thus functioned similarly to Schwann cells, promoting nerve regeneration.

The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model

“…Sections were stained with 0.5% (w/v) toluidine blue solution and examined by light microscopy (Nikon ECLIPSE 80i, Tokyo, Japan). Total myelinated axon number and measurements of the myelinated axon diameter, myelin thickness, and G-ratio were performed using ImageJ software (National Institutes of Health, Bethesda, MD, USA) for morphometric analysis, as reported in our previous studies [ 8 , 9 , 14 , 39 ]. Briefly, the total neural area ( a ) of each specimen was calculated by choosing six or seven fields at random so that the area analyzed would represent > 20% of the entire neural area of each specimen.…”

Immunohistologic analysis of spontaneous recurrent laryngeal nerve reinnervation in a rat model

“…Efforts to improve neural regeneration in general after a recognized nerve injury include primary coaptation, autologous nerve grafting, nerve conduits using an extracellular matrix, bone marrow‐derived cells to improve vascularity, supportive cells, gene therapy with growth factors, and even 3D printed scaffolds . Although some of these techniques hold promise in terms of promoting axonal growth, they do not address the problem of synkinesis.…”

Peripheral Nerve Regeneration

“…[213][214][215][216][217] Bone marrowderived mesenchymal stem cells have shown potential for transplantation in models of PNI and increased expression of markers for glial cell lineages, typically Schwann cell like, on exposure to suitable differentiation factors composed of a cocktail of growth factors and agents. 222,[226][227][228][229] The reason for the success of such an approach in the peripheral nerve regeneration milieu has been attributed to the ability of the differentiated mesenchymal stem cells to secrete critical neurotrophins 220,221 that have shown ability to upregulate myelin associated genes and proteins when cocultured with neuronal cells in an in vitro model. 215,[222][223][224][225] Several different biomaterials-based nerve conduits have been employed for in vivo delivery of the differentiated or undifferentiated mesenchymal stem cells.…”