Mesenchymal bone marrow stem cells within polyglycolic acid tube observed in vivo after six weeks enhance facial nerve regeneration

Abstract

Autografting is the gold-standard method for facial nerve repair with tissue loss. Its association with high-quality scaffolds and cell implants has disclosed distinct experimental outcomes. The aim of this study was to evaluate the functional and histological effects of bone marrow stem cells (BMSC) combined with polyglycolic acid tube (PGAt) in autografted rat facial nerves. After neurotmesis of the mandibular branch of the rat facial nerve, surgical repair consisted of nerve autografting (groups A-E) contained in pGAT (groups B-E), filled with basement membrane matrix (groups C-E) with undifferentiated BMSC (group D) or Schwann-like cells that had differentiated from BMSC (group E). Axon morphometrics and an objective compound muscle action potentials (CMAP) analysis were conducted. Immunofluorescence assays were carried out with Schwann cell marker S100 and anti-β-galactosidase to label exogenous cells. Six weeks after surgery, animals from either cell-containing group had mean CMAP amplitudes significantly higher than control groups. Differently from other groups, facial nerves with Schwann-like cell implants had mean axonal densities within reference values. This same group had the highest mean axonal diameter in distal segments. We observed expression of the reporter gene lacZ in nerve cells in the graft and distally from it in groups D and E. Group-E cells had lacZ coexpressed with S100. In conclusion, regeneration of the facial nerve was improved by BMSC within PGAt in rats, yet Schwann-like cells were associated with superior effects. Accordingly, groups D and E had BMSC integrated in neural tissue with maintenance of former cell phenotype for six weeks.

Combined polyglycolic acid tube and autografting versus autografting or polyglycolic acid tube alone. A comparative study of peripheral nerve regeneration in rats

“…Whenever the extension of tissue loss in peripheral nerve lesions do not allow for primary suture, the best repairing method seems to be autografting 2,13 . However, some important aspects to be considered include: 1) the need for resecting autologous tissue;…”

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

“…Also, they are major histocompatibility complex (MHC) class II negative and also their MHC class I expression levels can be manipulated; therefore they do not require the use of immunosuppressive drugs [217,218]. MSCs can be isolated from several origins, including skin, hair follicle, periosteum, amniotic fluid, umbilical cord blood adipose tissue and dental pulp [53,56,200,215,[219][220][221]. Bone marrow represents the most commonly used tissue source of adult MSCs.…”

“…Results showed that MSCs enhanced the recovery of sensory and motor function in neurotmesis injuries showing a thicker myelin sheath. Other authors have reported the application of bone marrow stem cells and Schwann-like cells in the regeneration of facial nerves in rats [219].…”

Sutura química por polietilenoglicol na regeneração do nervo facial em ratos após neurotmese

“…Existem vários modelos animais experimentais do NF, envolvendo cobaias, camundongos, primatas não humanos, cães, gatos e ratos, dentre outros (3,(27)(28)(29)(30)(31)(32)(33) (42). Além disso, defendem que a análise qualitativa, embora subjetiva, é uma interessante ferramenta quando aliada à análise quantitativa, dando ideia sobre a qualidade do tecido neural regenerado (42,50).…”

“…A técnica digital atual permite a contagem e medição das fibras mielinizadas a partir do software de análise de imagem (30,51).…”