Axonal regrowth through a collagen guidance channel bridging spinal cord to the avulsed C6 roots: Functional recovery in primates with brachial plexus injury

Liu, S.; Bodjarian, Nadia; Langlois, O.; Bonnard, Anne-Sophie; Boisset, Nazaire; Peulve, Pascal; Saïd, Gérard; Tadié, M

doi:10.1002/(sici)1097-4547(19980315)51:6<723::aid-jnr6>3.0.co;2-d

Cited by 38 publications

(7 citation statements)

References 40 publications

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“…An emerging strategy for replacing and/or regenerating damaged tissue is the implantation of stem cells and/or artificial biomaterials such as scaffolds to form tissue bridges between damaged spinal cord stumps. Recent preclinical studies include the implantation of foetal nervous tissue (Bregman, 1987), embryonic stem cells (Brustle et al, 1999), bone marrow mesenchymal stem cells (Prockop, 1997;Akiyama et al, 2002a;Jendelová et al, 2003Jendelová et al, , 2004b, Schwann cells (Kuhlengel et al, 1990), peripheral nervous tissue (Wrathall et al, 1982;Horvat, 1991), collagen-based matrices containing cells or neuroactive substances (Houweling et al, 1998;Liu et al, 1998), nitrocellulose membranes (Houle and Ziegler, 1994), tubes made from polymeric materials (Houle and Ziegler, 1994;Xu et al, 1997;Oudega et al, 2001), polymer hydrogels (Woerly et al, 1998(Woerly et al, , 2001aLesný et al, 2002;Jendelová et al, 2004a), and biodegradable polylactide implants (Maquet et al, 2001).…”

Section: Strategies For Spinal Cord Injury Treatmentmentioning

confidence: 99%

Bone Marrow Stem Cells and Polymer Hydrogels—Two Strategies for Spinal Cord Injury Repair

et al. 2006

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1. Emerging clinical studies of treating brain and spinal cord injury (SCI) led us to examine the effect of autologous adult stem cell transplantation as well as the use of polymer scaffolds in spinal cord regeneration. We compared an intravenous injection of mesenchymal stem cells (MSCs) or the injection of a freshly prepared mononuclear fraction of bone marrow cells (BMCs) on the treatment of an acute or chronic balloon-induced spinal cord compression lesion in rats. Based on our experimental studies, autologous BMC implantation has been used in a Phase I/II clinical trial in patients (n=20) with a transversal spinal cord lesion. 2. MSCs were isolated from rat bone marrow by their adherence to plastic, labeled with iron-oxide nanoparticles and expanded in vitro. Macroporous hydrogels based on derivatives of 2-hydroxyethyl methacrylate (HEMA) or 2-hydroxypropyl methacrylamide (HPMA) were prepared, then modified by their copolymerization with a hydrolytically degradable crosslinker, N,O-dimethacryloylhydroxylamine, or by different surface electric charges. Hydrogels or hydrogels seeded with MSCs were implanted into rats with hemisected spinal cords. 3. Lesioned animals grafted with MSCs or BMCs had smaller lesions 35 days postgrafting and higher scores in BBB testing than did control animals and also showed a faster recovery of sensitivity in their hind limbs using the plantar test. The functional improvement was more pronounced in MSC-treated rats. In MR images, the lesion populated by grafted cells appeared as a dark hypointense area and was considerably smaller than in control animals. Morphometric measurements showed an increase in the volume of spared white matter in cell-treated animals. In the clinical trial, we compared intraarterial (via a. vertebralis, n=6) versus intravenous administration of BMCs (n=14) in a group of subacute (10-33 days post-SCI, n=8) and chronic patients (2-18 months, n=12). For patient follow-up we used MEP, SEP, MRI, and the ASIA score. Our clinical study revealed that the implantation of BMCs into patients is safe, as there were no complications following cell administration. Partial improvement in the ASIA score and partial recovery of MEP or SEP have been observed in all subacute patients who received cells via a. vertebralis (n=4) and in one out of four subacute patients who received cells intravenously. Improvement was also found in one chronic patient who received cells via a. vertebralis. A much larger population of patients is needed before any conclusions can be drawn. The implantation of hydrogels into hemisected rat spinal cords showed that cellular ingrowth was most pronounced in copolymers of HEMA with a positive surface electric charge. Although most of the cells had the morphological properties of connective tissue elements, we found NF-160-positive axons invading all the implanted hydrogels from both the proximal and distal stumps. The biodegradable hydrogels degraded from the border that was in direct contact with the spinal cord tissue. They were resorbed by macr...

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Section: Strategies For Spinal Cord Injury Treatmentmentioning

confidence: 99%

Bone Marrow Stem Cells and Polymer Hydrogels—Two Strategies for Spinal Cord Injury Repair

et al. 2006

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“…Among these manipulations, implantation of a PN graft (Wu et al, 1994a, Holtzer et al, 1996Liu et al, 1998;Chai et al, 2000;Kassar-Duchossy et al, 2001;Rhrich-Haddout et al, 2001) or treatment with neurotrophic factors (Wu et al, 1995, Novikov et al, 1995Oorschot et al, 1998;Watabe et al, 2001) greatly enhanced survival. In those studies, the segment of nerve was usually implanted immediately following root avulsion.…”

Section: Survival Of Spinal Motoneurons Following Axonal Injurymentioning

confidence: 99%

Delayed Implantation of a Peripheral Nerve Graft Reduces Motoneuron Survival but Does Not Affect Regeneration following Spinal Root Avulsion in Adult Rats

Chai

Zhang

et al. 2004

Journal of Neurotrauma

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Adult spinal motoneurons can regenerate their axons into a peripheral nerve (PN) graft following root avulsion injury if the graft is implanted immediately after the lesion is induced. The present study was designed to determine how avulsed motoneurons respond to a PN graft if implantation takes place a few days to a few weeks later. Survival, regeneration, and gene expression changes of injured motoneurons after delayed PN graft implantation were studied. The survival rates of spinal motoneurons were 78%, 65%, 57%, or 53% if a PN graft was implanted immediately, 1, 2, or 3 weeks after root avulsion, respectively. Interestingly, most of the surviving motoneurons were able to regenerate their axons into the graft regardless of the delay. All regenerating motoneurons expressed p75, but not nNOS, while all motoneurons that failed to regenerate expressed nNOS, but not p75. p75 and nNOS may, therefore, be used as markers for success or failure to regenerate axons. In the group with immediate graft implantation, 85% of the surviving motoneurons extended axons into the PN graft, while in the groups in which implantation was delayed 1, 2, or 3 weeks, 84%, 82%, and 83% of the surviving motoneurons, respectively, were found to have regenerated into the grafts. These findings indicate that avulsed spinal motoneurons retain the ability to regenerate for at least 3 weeks, and perhaps for as long as they survive. Therefore, the delayed implantation of a PN graft after root avulsion may provide a continued conducive environment to support regeneration.

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“…24 A variant of a spinal cord bypass without using nerve transfers has been developed in rats 23,24 and later in primates. 20,21 In this model, the proximal terminus of peripheral nerve autografts is implanted into the ventral horn of the spinal cord below the level of injury, whereas the distal ends are anastomosed to the lumbar ventral nerve roots. Data from this model have suggested that anterior horn motor neurons send recovering axons down the nerve grafts to reinnervate the distal lumbar nerve-supplied targets.…”

Section: Spinal Cord Bypass: Animal Studiesmentioning

confidence: 99%

Spinal cord bypass surgery using peripheral nerve transfers: review of translational studies and a case report on its use following complete spinal cord injury in a human

Oppenheim

Spitzer

Winfree

2009

FOC

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Spinal cord injury has been studied in a variety of in vitro and in vivo animal models. One promising therapeutic approach involves the transfer of peripheral nerves originating above the level of injury into the spinal cord below the level of injury. A model of spinal cord injury in rodents has shown the growth of peripheral nerve fibers into the spinal cord, with the subsequent development of functional synaptic connections and limb movement. The authors of this paper are currently developing a similar model in felines to assess the cortical control of these novel repair pathways. In an effort to determine whether these neurotization techniques could translate to spinal cord injury in humans, the authors treated a patient by using intercostal nerve transfer following complete acute spinal cord injury. The case presented details a patient with paraplegia who regained partial motor and sensory activity following the transfer of intercostal nerves, originating above the level of the spinal cord injury, into the spinal canal below the level of injury. The patient recovered some of his motor and sensory function. Notably, his recovered hip flexion showed respiratory variation. This finding raises the possibility that intercostal nerve transfers may augment neurological recovery after complete spinal cord injury.

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Axonal regrowth through a collagen guidance channel bridging spinal cord to the avulsed C6 roots: Functional recovery in primates with brachial plexus injury

Cited by 38 publications

References 40 publications

Bone Marrow Stem Cells and Polymer Hydrogels—Two Strategies for Spinal Cord Injury Repair

Bone Marrow Stem Cells and Polymer Hydrogels—Two Strategies for Spinal Cord Injury Repair

Delayed Implantation of a Peripheral Nerve Graft Reduces Motoneuron Survival but Does Not Affect Regeneration following Spinal Root Avulsion in Adult Rats

Spinal cord bypass surgery using peripheral nerve transfers: review of translational studies and a case report on its use following complete spinal cord injury in a human

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