Surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model
In Europe and U.S.A. approximately 300,000 peripheral nerve injuries occur each year. Common causes of peripheral nerve injuries are direct mechanical trauma (transection, crush injury, traction, or avulsion), compression, thermal injury, and neurotoxins. Management of peripheral nerve injury...
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Anatomy Al-Timmemi, Hameed Ali Surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model |
| description |
In Europe and U.S.A. approximately 300,000 peripheral nerve injuries occur each
year. Common causes of peripheral nerve injuries are direct mechanical trauma
(transection, crush injury, traction, or avulsion), compression, thermal injury, and
neurotoxins. Management of peripheral nerve injury (PNI) requires an
understanding of the Anatomy, Pathology, Pathophysiology and surgical
principles. However, the rate of success of functional recovery from PNI is far
from satisfactory in spite of advances in microsurgery. The poor functional
recovery has been attributed to factors intrinsic to the motor or sensory cell body
and to elements at the site of injury including nerve gaps, scar tissue formation and inadequate time frame required for both supportive growth factors and
extracellular matrix molecules to be effective for nerve regeneration. Thus in this
study a comprehensive investigation was directed toward developing procedures
to improve nerve regeneration focusing on biological approaches to promote
nerve healing through: i) the role of omental pedicle in nerve regeneration and
functional recovery. ii) Isolation and identification of the mesenchymal stem
cells from bone marrow, which currently is the target of studies on tissue and
organ regeneration in view of their plasticity for nerve regeneration and
functional recovery.
This study was conducted with the hypothesis that omental pedicle transposition
(OMPT) and bone marrow stromal cells (BMSCs) implantation promote sciatic
nerve regeneration and functional recovery. Hence the objective of the study was
to investigate the effects of omental pedicle transposition and bone marrow
mesenchymal stem cells implantation on the sciatic nerve following neurotmesis
in a rabbit model. Towards this end, the investigation compares the efficacy of
omental pedicle transpositioning and mesenchymal stem cells implantation on
transected sciatic nerve. Evaluation of nerve regeneration brought about by each
treatment was based on clinical, neurohistological, ultrastructural,
histomorphometric examinations evaluation and relative gastrocnemius muscle
weight gain.Sixty healthy rabbits were used in the study. The animals were divided into three
equal groups (n=20) and subjected to coaptation of transected sciatic nerve with
epineural sutures (ENS) which served as control and omental pedicle
transposition (OMPT) and bone marrow stromal cells (BMSCs) implantation
comprising the treated groups. Evaluation on the regeneration and functional
recovery of the transected sciatic nerve based on the above approaches were
performed on days 14, 28, 56 and 112 post operations (PO).
Clinical and gross pathological examinations showed complete healing of the
skin incision of the operated limb with evidences of mild adhesion between the
coaptated sciatic nerve and the surrounding tissues in the BMSCs implanted
group while there was no evidence of adhesion in the OMPT group. Clinical
motor signs of the operated limb and walking in the OMPT and BMSCs
implanted groups showed earlier recovery compared to the control group on day
55 PO. Clinical signs were supported by the earlier registration of muscle
contractions force in both groups while regain of muscle mass ensued earlier in
the OMPT group. Sensory clinical signs indicated the progress of sensation on
day 112 PO in both the OMPT and BMSCs implanted groups.
Histopathological findings of the proximal segment of the sciatic nerve in the
OMPT and BMSCs implanted groups indicated early regeneration demonstrated
by parallel arrangement of nerve fibers, increased angiogenesis, increased
concentration of Schwann cells and minimal scar tissue formation on day 28 PO.Semi-thin sections of the proximal and distal segments of the transected nerve
showed normal arrangement and distribution of nerve fibers and normal
epineurium development. The dorsal root ganglia and spinal cord contained
neurons with Nissl bodies indicating nerve recovery of the OMPT and BMSCs
groups. Histopathological findings of the gastrocnemius muscle in the OMPT
and BMSCs groups showed progressive regeneration. These histopathological
finding of nerve tissue regeneration supported the clinical signs in the operated
limb.
Regeneration of nerve fibers was further strengthen by ultrastrutural finding of
the sciatic nerve which showed well-developed myelination, activated Schwann
cells, well-developed basement membrane and endoneurium which confirmed the
histological and pathophysiological regeneration of the transected sciatic nerve in
the OMPT and BMSCs groups.
Histomorphometric analysis showed an increase in the number of myelinated
nerve fibers, increased diameter of myelinated nerve fiber and increased thickness
of myelin sheath and axon diameter in the OMPT and BMSCs groups, indicating
sound reinnervation of the transected nerve. However, regenerative changes in
the OMPT group occurred slightly earlier compared to the BMSCs group. This
could indicate that omental pedicle transposition has a slight advantage over
stromal cell implant in terms of transected nerve therapy. Gastrocnemius muscle mass weight gain progressed to normal in the OMPT and BMSC groups indicated
the reinnervation of the gastrocnemius muscle.
The findings of this study provided ample evidences that surgical application of
omental pedicle transposition and bone marrow stem cells implantation on
injured peripheral nerve could promote early regeneration and functional
recovery of the transected nerve. Thus, there is tremendous potential in the
application of OMPT and BMSCs implantation in the treatment of peripheral
nerve injuries. |
| format |
Thesis |
| qualification_level |
Doctorate |
| author |
Al-Timmemi, Hameed Ali |
| author_facet |
Al-Timmemi, Hameed Ali |
| author_sort |
Al-Timmemi, Hameed Ali |
| title |
Surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model |
| title_short |
Surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model |
| title_full |
Surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model |
| title_fullStr |
Surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model |
| title_full_unstemmed |
Surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model |
| title_sort |
surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model |
| granting_institution |
Universiti Putra Malaysia |
| publishDate |
2011 |
| url |
http://psasir.upm.edu.my/id/eprint/70087/1/FPV%202011%2012%20-%20IR.pdf |
| _version_ |
1747812757012480000 |
| spelling |
my-upm-ir.700872019-11-12T02:21:45Z Surgical, clinical and pathological comparison on the used of omental pedicle and bone marrow stroma cell therapy following sciatic nerve neurotmesis in rabbit model 2011-10 Al-Timmemi, Hameed Ali In Europe and U.S.A. approximately 300,000 peripheral nerve injuries occur each year. Common causes of peripheral nerve injuries are direct mechanical trauma (transection, crush injury, traction, or avulsion), compression, thermal injury, and neurotoxins. Management of peripheral nerve injury (PNI) requires an understanding of the Anatomy, Pathology, Pathophysiology and surgical principles. However, the rate of success of functional recovery from PNI is far from satisfactory in spite of advances in microsurgery. The poor functional recovery has been attributed to factors intrinsic to the motor or sensory cell body and to elements at the site of injury including nerve gaps, scar tissue formation and inadequate time frame required for both supportive growth factors and extracellular matrix molecules to be effective for nerve regeneration. Thus in this study a comprehensive investigation was directed toward developing procedures to improve nerve regeneration focusing on biological approaches to promote nerve healing through: i) the role of omental pedicle in nerve regeneration and functional recovery. ii) Isolation and identification of the mesenchymal stem cells from bone marrow, which currently is the target of studies on tissue and organ regeneration in view of their plasticity for nerve regeneration and functional recovery. This study was conducted with the hypothesis that omental pedicle transposition (OMPT) and bone marrow stromal cells (BMSCs) implantation promote sciatic nerve regeneration and functional recovery. Hence the objective of the study was to investigate the effects of omental pedicle transposition and bone marrow mesenchymal stem cells implantation on the sciatic nerve following neurotmesis in a rabbit model. Towards this end, the investigation compares the efficacy of omental pedicle transpositioning and mesenchymal stem cells implantation on transected sciatic nerve. Evaluation of nerve regeneration brought about by each treatment was based on clinical, neurohistological, ultrastructural, histomorphometric examinations evaluation and relative gastrocnemius muscle weight gain.Sixty healthy rabbits were used in the study. The animals were divided into three equal groups (n=20) and subjected to coaptation of transected sciatic nerve with epineural sutures (ENS) which served as control and omental pedicle transposition (OMPT) and bone marrow stromal cells (BMSCs) implantation comprising the treated groups. Evaluation on the regeneration and functional recovery of the transected sciatic nerve based on the above approaches were performed on days 14, 28, 56 and 112 post operations (PO). Clinical and gross pathological examinations showed complete healing of the skin incision of the operated limb with evidences of mild adhesion between the coaptated sciatic nerve and the surrounding tissues in the BMSCs implanted group while there was no evidence of adhesion in the OMPT group. Clinical motor signs of the operated limb and walking in the OMPT and BMSCs implanted groups showed earlier recovery compared to the control group on day 55 PO. Clinical signs were supported by the earlier registration of muscle contractions force in both groups while regain of muscle mass ensued earlier in the OMPT group. Sensory clinical signs indicated the progress of sensation on day 112 PO in both the OMPT and BMSCs implanted groups. Histopathological findings of the proximal segment of the sciatic nerve in the OMPT and BMSCs implanted groups indicated early regeneration demonstrated by parallel arrangement of nerve fibers, increased angiogenesis, increased concentration of Schwann cells and minimal scar tissue formation on day 28 PO.Semi-thin sections of the proximal and distal segments of the transected nerve showed normal arrangement and distribution of nerve fibers and normal epineurium development. The dorsal root ganglia and spinal cord contained neurons with Nissl bodies indicating nerve recovery of the OMPT and BMSCs groups. Histopathological findings of the gastrocnemius muscle in the OMPT and BMSCs groups showed progressive regeneration. These histopathological finding of nerve tissue regeneration supported the clinical signs in the operated limb. Regeneration of nerve fibers was further strengthen by ultrastrutural finding of the sciatic nerve which showed well-developed myelination, activated Schwann cells, well-developed basement membrane and endoneurium which confirmed the histological and pathophysiological regeneration of the transected sciatic nerve in the OMPT and BMSCs groups. Histomorphometric analysis showed an increase in the number of myelinated nerve fibers, increased diameter of myelinated nerve fiber and increased thickness of myelin sheath and axon diameter in the OMPT and BMSCs groups, indicating sound reinnervation of the transected nerve. However, regenerative changes in the OMPT group occurred slightly earlier compared to the BMSCs group. This could indicate that omental pedicle transposition has a slight advantage over stromal cell implant in terms of transected nerve therapy. Gastrocnemius muscle mass weight gain progressed to normal in the OMPT and BMSC groups indicated the reinnervation of the gastrocnemius muscle. The findings of this study provided ample evidences that surgical application of omental pedicle transposition and bone marrow stem cells implantation on injured peripheral nerve could promote early regeneration and functional recovery of the transected nerve. Thus, there is tremendous potential in the application of OMPT and BMSCs implantation in the treatment of peripheral nerve injuries. Anatomy 2011-10 Thesis http://psasir.upm.edu.my/id/eprint/70087/ http://psasir.upm.edu.my/id/eprint/70087/1/FPV%202011%2012%20-%20IR.pdf text en public doctoral Universiti Putra Malaysia Anatomy |