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

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.

[1]  M. Wiberg,et al.  Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage , 2006, Glia.

[2]  S. Mackinnon,et al.  Experimental study of chronic nerve compression. Clinical implications. , 1986, Hand clinics.

[3]  Masahiko Takano,et al.  Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone‐marrow stromal cells , 2001, The European journal of neuroscience.

[4]  S. Hsu,et al.  Transplantation of bone marrow stromal cells for peripheral nerve repair , 2007, Experimental Neurology.

[5]  M. Wiberg,et al.  Addition of fibronectin to alginate matrix improves peripheral nerve regeneration in tissue-engineered conduits. , 2003, Tissue engineering.

[6]  R. Weber,et al.  A Randomized Prospective Study of Polyglycolic Acid Conduits for Digital Nerve Reconstruction in Humans , 2000, Plastic and reconstructive surgery.

[7]  L. A. Haddad,et al.  Retention of progenitor cell phenotype in otospheres from guinea pig and mouse cochlea , 2010, Journal of Translational Medicine.

[8]  D. Prockop,et al.  Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats--similarities to astrocyte grafts. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. Ferreira,et al.  POLYGLYCOLIC ACID TUBE ASSOCIATED WITH GM 1 IN REGENERATION OF PERIPHERAL NERVES , 2022 .

[10]  Catherine M. Verfaillie,et al.  Pluripotency of mesenchymal stem cells derived from adult marrow , 2007, Nature.

[11]  K. Marra,et al.  Injectable systems and implantable conduits for peripheral nerve repair , 2012, Biomedical materials.

[12]  G. Keilhoff,et al.  Comparison of different biogenic matrices seeded with cultured Schwann cells for bridging peripheral nerve defects , 2004, Neurological research.

[13]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[14]  Y. Wei,et al.  Schwann‐like cell differentiation of rat adipose‐derived stem cells by indirect co‐culture with Schwann cells in vitro , 2010, Cell proliferation.

[15]  Coert Jh,et al.  Synthetic nerve guide implants in humans: a comprehensive survey. , 2007 .

[16]  Zheng-rong Chen,et al.  Fabricating autologous tissue to engineer artificial nerve , 2002, Microsurgery.

[17]  Richard L. Sidman,et al.  Increased rate of peripheral nerve regeneration using bioresorbable nerve guides and a laminin-containing gel , 1985, Experimental Neurology.

[18]  Susan E. Mackinnon,et al.  Clinical Nerve Reconstruction with a Bioabsorbable Polyglycolic Acid Tube , 1990, Plastic and reconstructive surgery.

[19]  W. Mandemakers,et al.  The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development. , 2003, Genes & development.

[20]  B. Strauss,et al.  Bone marrow stem cells in facial nerve regeneration from isolated stumps , 2013, Muscle & nerve.

[21]  M. Ferreira,et al.  Results of reconstruction of the facial nerve , 1994, Microsurgery.

[22]  M. Chao,et al.  Nuclear Localization of the p75 Neurotrophin Receptor Intracellular Domain*♦ , 2009, The Journal of Biological Chemistry.

[23]  L. Scaramella,et al.  Traumatic peripheral facial palsy. , 1978, Ear, nose, & throat journal.

[24]  R. Bento,et al.  Comparison between fibrin tissue adhesive, epineural suture and natural union in intratemporal facial nerve of cats. , 1989, Acta oto-laryngologica. Supplementum.

[25]  G. Korn,et al.  Posttraumatic facial nerve regeneration in rabbits. , 2006, Brazilian journal of otorhinolaryngology.

[26]  F. Rodrı́guez,et al.  FK506 enhances regeneration of axons across long peripheral nerve gaps repaired with collagen guides seeded with allogeneic Schwann cells , 2004, Glia.

[27]  R. Bento,et al.  Assessment of a Neurophysiological Model of the Mandibular Branch of the Facial Nerve in Rats by Electromyography , 2012, The Annals of otology, rhinology, and laryngology.

[28]  David L Kaplan,et al.  Biomaterials for the development of peripheral nerve guidance conduits. , 2012, Tissue engineering. Part B, Reviews.

[29]  J. Olson,et al.  Differentiation of mesenchymal stem cells to support peripheral nerve regeneration in a rat model , 2011, Experimental Neurology.

[30]  B. Schlosshauer,et al.  Synthetic Nerve Guide Implants in Humans: A Comprehensive Survey , 2006, Neurosurgery.

[31]  C. D. Silva,et al.  Quantitative histological analysis of the mandibular branch of the facial nerve in rats. , 2012, Acta cirurgica brasileira.

[32]  E. Shooter,et al.  The Neurotrophin Receptor p75NTR as a Positive Modulator of Myelination , 2002, Science.

[33]  Chao Zhao,et al.  Expression of the POU-Domain Transcription Factors SCIP/Oct-6 and Brn-2 Is Associated with Schwann Cell but Not Oligodendrocyte Remyelination of the CNS , 2002, Molecular and Cellular Neuroscience.

[34]  R. Mirsky,et al.  The origin and development of glial cells in peripheral nerves , 2005, Nature Reviews Neuroscience.

[35]  Takuya Hayashi,et al.  Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration , 2010, Experimental Neurology.

[36]  Marcus Castro Ferreira,et al.  Tubo de ácido poliglicólico e GM1 na regeneração de nervos periféricos , 2009 .

[37]  F. Ding,et al.  Bone marrow mesenchymal stem cells promote cell proliferation and neurotrophic function of Schwann cells in vitro and in vivo , 2009, Brain Research.

[38]  D. Faber,et al.  Axotomy-induced alterations in the electrophysiological characteristics of neurons , 1990, Progress in Neurobiology.

[39]  M. Dujovny,et al.  Peripheral nerve regeneration by bone marrow stromal cells , 2002, Neurological research.

[40]  C. F. da Silva,et al.  Evaluation of the systemic use of riluzole in post-traumatic facial nerve regeneration: experimental study in rabbits , 2007, Acta oto-laryngologica.

[41]  M. C. Rodrigues,et al.  Peripheral Nerve Repair with Cultured Schwann Cells: Getting Closer to the Clinics , 2012, TheScientificWorldJournal.

[42]  D. Alessi,et al.  S100 is preferentially distributed in myelin-forming Schwann cells , 1990, Journal of neurocytology.

[43]  Sujeong Jang,et al.  Effect of neural‐induced mesenchymal stem cells and platelet‐rich plasma on facial nerve regeneration in an acute nerve injury model , 2010, The Laryngoscope.

[44]  Mari Dezawa,et al.  Peripheral nerve regeneration by transplantation of BMSC-derived Schwann cells as chitosan gel sponge scaffolds. , 2009, Journal of biomedical materials research. Part A.

[45]  R. Bento,et al.  Anastomosis of the Intratemporal Facial Nerve Using Fibrin Tissue Adhesive , 1993, Ear, nose, & throat journal.

[46]  Antonios G Mikos,et al.  Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration. , 2002, Biomaterials.

[47]  H. Schmalbruch,et al.  Fiber composition of the rat sciatic nerve , 1986, The Anatomical record.

[48]  A. Irintchev,et al.  Factors limiting motor recovery after facial nerve transection in the rat: combined structural and functional analyses , 2005, The European journal of neuroscience.

[49]  A. Lavdas,et al.  Schwann cell transplantation for CNS repair. , 2008, Current medicinal chemistry.

[50]  T M Mayhew,et al.  Sampling schemes for estimating nerve fibre size. I. Methods for nerve trunks of mixed fascicularity. , 1984, Journal of anatomy.

[51]  G. Terenghi,et al.  Schwann cell mediated trophic effects by differentiated mesenchymal stem cells. , 2008, Experimental cell research.

[52]  Jeff Biernaskie,et al.  Skin-Derived Precursors Generate Myelinating Schwann Cells for the Injured and Dysmyelinated Nervous System , 2006, The Journal of Neuroscience.

[53]  Liang Zhou,et al.  Transplantation of neural stem cells overexpressing glia-derived neurotrophic factor promotes facial nerve regeneration , 2009, Acta oto-laryngologica.

[54]  E. Luo,et al.  Schwann-like mesenchymal stem cells within vein graft facilitate facial nerve regeneration and remyelination , 2011, Brain Research.

[55]  R. Sidman,et al.  Peripheral nerve regeneration with entubulation repair: Comparison of biodegradeable nerve guides versus polyethylene tubes and the effects of a laminin-containing gel , 1987, Experimental Neurology.