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

2008 ◽  
Vol 389 (7) ◽  
Author(s):  
Maria Grosheva ◽  
Orlando Guntinas-Lichius ◽  
Stephan Arnhold ◽  
Emmanouil Skouras ◽  
Stefanie Kuerten ◽  
...  

AbstractRecently, 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.

2009 ◽  
Vol 191 (4) ◽  
pp. 356-370 ◽  
Author(s):  
Nektarios Sinis ◽  
Frauke Horn ◽  
Borislav Genchev ◽  
Emmanouil Skouras ◽  
Daniel Merkel ◽  
...  

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Kirsten Haastert ◽  
Maria Grosheva ◽  
Srebrina K. Angelova ◽  
Orlando Guntinas-Lichius ◽  
Emmanouil Skouras ◽  
...  

Purpose. To determine whether transplantation of Schwann cells (SCs) overexpressing different isoforms of fibroblast growth factor 2 (FGF-2) combined with manual stimulation (MS) of vibrissal muscles improves recovery after facial nerve transection in adult rat.Procedures. Transected facial nerves were entubulated with collagen alone or collagen plus naïve SCs or transfected SCs. Half of the rats received daily MS. Collateral branching was quantified from motoneuron counts after retrograde labeling from 3 facial nerve branches. Quality assessment of endplate reinnervation was combined with video-based vibrissal function analysis.Results. There was no difference in the extent of collateral axonal branching. The proportion of polyinnervated motor endplates for either naïve SCs or FGF-2 over-expressing SCs was identical. Postoperative MS also failed to improve recovery.Conclusions. Neither FGF-2 isoform changed the extent of collateral branching or polyinnervation of motor endplates; furthermore, this motoneuron response could not be overridden by MS.


2007 ◽  
Vol 28 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Orlando Guntinas-Lichius ◽  
Gregor Hundeshagen ◽  
Thomas Paling ◽  
Michael Streppel ◽  
Maria Grosheva ◽  
...  

2009 ◽  
Vol 39 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Anna Bischoff ◽  
Maria Grosheva ◽  
Andrey Irintchev ◽  
Emmanouil Skouras ◽  
Katerina Kaidoglou ◽  
...  

Neurosurgery ◽  
2007 ◽  
Vol 61 (6) ◽  
pp. 1276-1285 ◽  
Author(s):  
Orlando Guntinas-Lichius ◽  
Gregor Hundeshagen ◽  
Thomas Paling ◽  
Doychin N. Angelov

Abstract OBJECTIVE Poor functional recovery after facial nerve reconstruction is characterized by mass movements and synkinesis. Major reasons are axonal sprouting from the regenerating axons leading to misdirected reinnervation and hyperinnervation as well as polyinnervation of the mimic muscle end plates. We analyzed whether or not the type of nerve reconstruction influenced these pathological phenomena. METHODS The experiments were performed on 48 adult rats divided into four groups. One group served as an intact control and the experimental groups were subjected to facial-facial nerve repair (FFN), facial nerve interpositional grafting, and hypoglossal-facial nerve repair (HFN), with 12 subjects in each group. Two months later, functional recovery was measured by biometrical motion analysis of whisking. Retrograde fluorescence labeling of the brainstem motoneurons was used to quantify the degree of collateral axonal branching at the lesion site. Fluorescence histochemistry of sections through the levator labii superioris muscle was performed to quantify the degree of polyinnervation after surgery. RESULTS The type of nerve reconstruction significantly influenced the regeneration. The whisking amplitude did not recover completely regardless of the type of reconstruction. The angular velocity and angular acceleration of the vibrissal hairs showed a full recovery after facial nerve interpositional grafting and HFN, whereas these parameters remained decreased after FFN. Significantly less collateral branching and polyinnervation of the end plates were determined after grafting and HFN than after FFN. CONCLUSION No type of immediate facial nerve reconstruction results in a full recovery in the rat. However, the morphological and functional recovery was significantly better after grafting and HFN than after FFN.


Neurosurgery ◽  
2012 ◽  
Vol 70 (6) ◽  
pp. 1544-1556 ◽  
Author(s):  
Arzu Hizay ◽  
Umut Ozsoy ◽  
Bahadir Murat Demirel ◽  
Ozlem Ozsoy ◽  
Srebrina K. Angelova ◽  
...  

Abstract BACKGROUND: Despite increased understanding of peripheral nerve regeneration, functional recovery after surgical repair remains disappointing. A major contributing factor is the extensive collateral branching at the lesion site, which leads to inaccurate axonal navigation and aberrant reinnervation of targets. OBJECTIVE: To determine whether the Y tube reconstruction improved axonal regrowth and whether this was associated with improved function. METHODS: We used a Y-tube conduit with the aim of improving navigation of regenerating axons after facial nerve transection in rats. RESULTS: Retrograde labeling from the zygomatic and buccal branches showed a halving in the number of double-labeled facial motor neurons (15% vs 8%; P < .05) after Y tube reconstruction compared with facial-facial anastomosis coaptation. However, in both surgical groups, the proportion of polyinnervated motor endplates was similar (∼30%; P > .05), and video-based motion analysis of whisking revealed similarly poor function. CONCLUSION: Although Y-tube reconstruction decreases axonal branching at the lesion site and improves axonal navigation compared with facial-facial anastomosis coaptation, it fails to promote monoinnervation of motor endplates and confers no functional benefit.


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