Biological behavior of mesenchymal stem cells on poly-ε-caprolactone filaments and a strategy for tissue engineering of segments of the peripheral nerves

Abstract

IntroductionPeripheral nerves may fail to regenerate across tube implants because these lack the microarchitecture of native nerves. Bone marrow mesenchymal stem cells (MSC) secrete soluble factors that improve the regeneration of the peripheral nerves. Also, microstructured poly-caprolactone (PCL) filaments are capable of inducing bands of Büngner and promote regeneration in the peripheral nervous system (PNS). We describe here the interaction between PCL filaments and MSC, aiming to optimize PNS tubular implants.MethodsMSC were plated on PCL filaments for 48 h and the adhesion profile, viability, proliferation and paracrine capacity were evaluated. Also, Schwann cells were plated on PCL filaments covered with MSC for 24 h to analyze the feasibility of the co-culture system. Moreover, E16 dorsal root ganglia were plated in contact with PCL filaments for 4 days to analyze neurite extension. Right sciatic nerves were exposed and a 10 mm nerve segment was removed. Distal and proximal stumps were reconnected inside a 14-mm polyethylene tube, leaving a gap of approximately 13 mm between the two stumps. Animals then received phosphate-buffered saline 1×, PCL filaments or PCL filaments previously incubated with MSC and, after 12 weeks, functional gait performance and histological analyses were made. Statistical analyses were made using Student’s unpaired t-test, one-way analysis of variance (ANOVA) or two-way ANOVA followed by Bonferroni post-test.ResultsMSC were confined to lateral areas and ridges of PCL filaments, aligning along the longitudinal. MSC showed high viability (90 %), and their proliferation and secretion capabilities were not completely inhibited by the filaments. Schwann cells adhered to filaments plated with MSC, maintaining high viability (90 %). Neurites grew and extended over the surface of PCL filaments, reaching greater distances when over MSC-plated filaments. Axons showed more organized and myelinized fibers and reinnervated significantly more muscle fibers when they were previously implanted with MSC-covered PLC filaments. Moreover, animals with MSC-covered filaments showed increased functional recovery after 12 weeks.ConclusionsWe provide evidence for the interaction among MSC, Schwann cells and PCL filaments, and we also demonstrate that this system can constitute a stable and permissive support for regeneration of segments of the peripheral nerves.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0121-2) contains supplementary material, which is available to authorized users.

Neural Progenitor-Like Cells Induced from Human Gingiva-Derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells in Rat Sciatic Nerve Regeneration

“…These unique pleiotropic properties of MSCs have made them good candidates for an allogeneic cell source in regenerative medicine. Accumulating evidence has implied that MSCs derived from tissues , particularly from dental pulp , , , confer beneficial effects on peripheral nerve regeneration. Mechanistically, MSC‐mediated beneficial effects on peripheral nerve regeneration have multiple facets, which may involve their multipotent transdifferentiation into different lineages of neuronal and glial cells (particularly regenerative Schwann cells) , , , , their paracrine neurotrophic , , and proangiogenic , , effects, and their immunomodulatory/ anti‐inflammatory and antifibrosis properties , .…”

“…Among various types of stem cells, NSCs are considered an ideal seed candidate for cell‐based treatment of nerve injury and neurodegenerative diseases; however, it remains a challenge to generate enough transplantable NSCs for clinical application. Alternatively, other types of adult stem cells, particularly mesenchymal stem cells (MSCs) isolated from different tissues such as bone marrow , adipose tissue , skeletal muscle , , and dental pulp , also confer properties to transdifferentiate into neuronal and glial progenies and produce neurotrophic factors, serving as relevant sources for stem cell‐based therapy in peripheral nerve injury (PNI) , , . However, the high heterogeneity, limited and variable neural differentiation and survival abilities, unpredictable cell fate, and variation of clinical outcomes significantly hinder the clinical application of MSCs in peripheral nerve regeneration.…”

Advances in Controlling Differentiation of Adult Stem Cells for Peripheral Nerve Regeneration

“…The use of conduits made from different synthetic polymers, either alone or in combination (i.e. (Poly-3-hydroxybutyrate (PHB) [53] , microstructured poly-caprolactone (PCL) [169] , poly (DL-lactide-e-caprolactone) copolyester based commercial conduit (Vivosorb, PLC) [167] ) with stem cells also promoted nerve regeneration, myelination and reinnervation through released growth factors, indirect effect on endogenous SCs activity or upregulation of expression for certain genes or pathways such as netrin-1, ninjurin, BDNF, GDNF, VEGF and angiopoitin-1. However, they did not enhance the in situ differentiation potential of the transplanted stem cells.…”

Testosterone propionate can promote effects of acellular nerve allograft‐seeded bone marrow mesenchymal stem cells on repairing canine sciatic nerve

“…Nie et al found that in a tissue‐engineered nerve group (consisting of rat jaw bones‐derived MSCs that were induced into SCs in vitro and PLGA scaffold), nerve regeneration was found to be significantly improved compared with a PLGA group for 10‐mm rat sciatic nerve defects (Nie et al, ). In this study, it was also shown that the regenerated nerve in the MSC–SC–PCL group (MSC was inoculated on PCL scaffold and then SCs were introduced for coculture for 24 hr after 48 hr) was longer than the MSC–PCL group in a rat sciatic nerve defect (Carrier‐Ruiz, Evaristo‐Mendonca, Mendez‐Otero, & Ribeiro‐Resende, ). Yu et al used adipose‐derived stem cells‐seeded bio‐conduits that was fabricated by 3D printing technique using cryopolymerized gelatin methacryloyl gel to treat 10‐mm rat sciatic nerve defect (Hu et al, ).…”