The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries

2012 ◽  
Vol 117 (4) ◽  
pp. 787-794 ◽  
Author(s):  
Shin Ohtsubo ◽  
Masakazu Ishikawa ◽  
Naosuke Kamei ◽  
Yasumu Kijima ◽  
Osami Suzuki ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Peripheral Blood ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Group 4 ◽  
Group 1

Object CD133+ cells have the potential to enhance histological and functional recovery from peripheral nerve injury. However, the number of CD133+ cells safely obtained from human peripheral blood is extremely limited. To address this issue, the authors expanded CD133+ cells derived from human peripheral blood using the serum-free expansion culture method and transplanted these ex vivo expanded cells into a model of sciatic nerve defect in rats. The purpose of this study was to determine the potential of ex vivo expanded CD133+ cells to induce or enhance the repair of injured peripheral nerves. Methods Phosphate-buffered saline (PBS group [Group 1]), 105 fresh CD133+ cells (fresh group [Group 2]), 105 ex vivo expanded CD133+ cells (expansion group [Group 3]), or 104 fresh CD133+ cells (low-dose group [Group 4]) embedded in atelocollagen gel were transplanted into a silicone tube that was then used to bridge a 15-mm defect in the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery, histological and functional evaluations of the regenerated tissues were performed. Results After 1 week of expansion culture, the number of cells increased 9.6 ± 3.3–fold. Based on the fluorescence-activated cell sorting analysis, it was demonstrated that the initial freshly isolated CD133+ cell population contained 93.22% ± 0.30% CD133+ cells and further confirmed that the expanded cells had a purity of 59.02% ± 1.58% CD133+ cells. However, the histologically and functionally regenerated nerves bridging the defects were recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The nerves did not regenerate to bridge the defect in any of the rats in Group 1. Conclusions The authors' results show that ex vivo expanded CD133+ cells derived from human peripheral blood have a therapeutic potential similar to fresh CD133+ cells for peripheral nerve injuries. The ex vivo procedure that can be used to expand CD133+ cells without reducing their function represents a novel method for developing cell therapy for nerve defects in a clinical setting.

scholarly journals Stabilization, Rolling, and Addition of Other Extracellular Matrix Proteins to Collagen Hydrogels Improve Regeneration in Chitosan Guides for Long Peripheral Nerve Gaps in Rats

Neurosurgery ◽  
2017 ◽  
Vol 80 (3) ◽  
pp. 465-474 ◽  
Author(s):  
Francisco Gonzalez-Perez ◽  
Stefano Cobianchi ◽  
Claudia Heimann ◽  
James B. Phillips ◽  
Esther Udina ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Standard Technique ◽  
Biologically Active ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Critical Gap ◽  
The Right

Abstract BACKGROUND: Autograft is still the gold standard technique for the repair of long peripheral nerve injuries. The addition of biologically active scaffolds into the lumen of conduits to mimic the endoneurium of peripheral nerves may increase the final outcome of artificial nerve devices. Furthermore, the control of the orientation of the collagen fibers may provide some longitudinal guidance architecture providing a higher level of mesoscale tissue structure. OBJECTIVE: To evaluate the regenerative capabilities of chitosan conduits enriched with extracellular matrix-based scaffolds to bridge a critical gap of 15 mm in the rat sciatic nerve. METHODS: The right sciatic nerve of female Wistar Hannover rats was repaired with chitosan tubes functionalized with extracellular matrix-based scaffolds fully hydrated or stabilized and rolled to bridge a 15 mm nerve gap. Recovery was evaluated by means of electrophysiology and algesimetry tests and histological analysis 4 months after injury. RESULTS: Stabilized constructs enhanced the success of regeneration compared with fully hydrated scaffolds. Moreover, fibronectin-enriched scaffolds increased muscle reinnervation and number of myelinated fibers compared with laminin-enriched constructs. CONCLUSION: A mixed combination of collagen and fibronectin may be a promising internal filler for neural conduits for the repair of peripheral nerve injuries, and their stabilization may increase the quality of regeneration over long gaps.

scholarly journals Sciatic nerve regeneration induced by glycosaminoglycan and laminin mimetic peptide nanofiber gels

RSC Advances ◽  
2016 ◽  
Vol 6 (112) ◽  
pp. 110535-110547 ◽  
Author(s):  
Busra Mammadov ◽  
Melike Sever ◽  
Mevhibe Gecer ◽  
Fatih Zor ◽  
Sinan Ozturk ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Bioactive Peptide ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Mimetic Peptide ◽  
The Usa ◽  
Sciatic Nerve Regeneration

Bioactive peptide gels enhance the regeneration of peripheral nerve injuries, which affect 20 million patients in the USA.

A PERIPHERAL NERVE INJURY MODEL UTILIZING A SIMPLE TISSUE SPARING APPROACH TO THE RABBIT SCIATIC NERVE

2018 ◽  
Vol 21 (01) ◽  
pp. 1850002
Author(s):  
Andrew J. Miller ◽  
Jacob Tulipan ◽  
Mark Wang ◽  
Pedro Beredjiklian ◽  
Andrzej Fertala ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Rabbit Model ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Muscle Sparing ◽  
Tissue Sparing ◽  
Injury Models

Background & Aims: Peripheral nerve injury models require a reproducible surgical technique that provides a simple and extensile peripheral nerve exposure. We present a muscle sparing apprach to the sciatic nerve in a rabbit model. A combination of general anestheia, sedative and perioperative analgesics was given to minimize animal discomfort. Methods: A posterior lateral dissection of the rabbit hind leg was performed to expose the proximal sciatic nerve. This facilitated an extensile dissection of both the proximal and distal sciatic nerve. Results: The described dissection is atraumatic, bloodless, and yields minimal postoperative morbidity on the rabbit. All rabbits received standard postoperative care in compliance with all regulatory agencies. A full vetinarian staff was available to manage the animals postoperatively. Conclusion: We found that our technique is a reproducible and easy to perform surgical approach with basic surgical setup. Our animal model provides an opportunity to evaluate and study peripheral nerve injuries peripheral nerve injuries.

Peripheral Nerve Injuries of the Shoulder in the Athlete

1990 ◽  
Vol 9 (2) ◽  
pp. 331-342 ◽  
Author(s):  
Francis X. Mendoza ◽  
Kenneth Main
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries

scholarly journals Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons

2011 ◽  
Vol 106 (5) ◽  
pp. 2450-2470 ◽  
Author(s):  
Francisco J. Alvarez ◽  
Haley E. Titus-Mitchell ◽  
Katie L. Bullinger ◽  
Michal Kraszpulski ◽  
Paul Nardelli ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Cell Body ◽  
Peripheral Nerve Injury ◽  
Motor Coordination ◽  
Electrophysiological Study ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Ia Afferent ◽  
Axon Collaterals

Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75–95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons.

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