title: Bone marrow-derived mesenchymal stem cell transplantation does not improve quality of muscle reinnervation or recovery of motor function after facial nerve transection in rats.
abstract: Recently, we devised and validated a novel strategy in rats to improve the outcome of facial nerve reconstruction by daily manual stimulation of the target muscles. The treatment resulted in full recovery of facial movements (whisking), which was achieved by reducing the proportion of pathologically polyinnervated motor endplates. Here, we posed whether manual stimulation could also be beneficial after a surgical procedure potentially useful for treatment of large peripheral nerve defects, i.e., entubulation of the transected facial nerve in a conduit filled with suspension of isogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) in collagen. Compared to control treatment with collagen only, entubulation with BM-MSCs failed to decrease the extent of collateral axonal branching at the lesion site and did not improve functional recovery. Post-operative manual stimulation of vibrissal muscles also failed to promote a better recovery following entubulation with BM-MSCs. We suggest that BM-MSCs promote excessive trophic support for regenerating axons which, in turn, results in excessive collateral branching at the lesion site and extensive polyinnervation of the motor endplates. Furthermore, such deleterious effects cannot be overridden by manual stimulation. We conclude that entubulation with BM-MSCs is not beneficial for facial nerve repair.
authors.affiliation: Department of Otorhinolaryngology, University of Cologne, Cologne, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Grosheva
authors.forename: Orlando
authors.initials: O
authors.lastname: Guntinas-Lichius
authors.forename: Stephan
authors.initials: S
authors.lastname: Arnhold
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Skouras
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuerten
authors.forename: Michael
authors.initials: M
authors.lastname: Streppel
authors.forename: Srebrina K
authors.initials: SK
authors.lastname: Angelova
authors.forename: Konstantin
authors.initials: K
authors.lastname: Wewetzer
authors.forename: Christine
authors.initials: C
authors.lastname: Radtke
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Dunlop
authors.forename: Doychin N
authors.initials: DN
authors.lastname: Angelov
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology*; D005154:Facial Nerve / Q000503:physiopathology*; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation; D009043:Motor Activity; D009045:Motor Endplate / Q000503:physiopathology; D009132:Muscles / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology*; D026201:Musculoskeletal Manipulations; D020221:Optic Nerve Injuries / Q000601:surgery* / Q000628:therapy; D011182:Postoperative Care; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D014738:Vibrissae