Gene transfer to schwann cells after peripheral nerve injury: A delivery system for therapeutic agents

1998 ◽  
Vol 43 (2) ◽  
pp. 205-211 ◽  
Author(s):  
Jesper Sørensen ◽  
Georg Haase ◽  
Christian Krarup ◽  
Helene Gilgenkrantz ◽  
Axel Kahn ◽  
...  
2013 ◽  
Vol 119 (3) ◽  
pp. 720-732 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Ranjan Gupta ◽  
Allan D. Levi

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.


1987 ◽  
Vol 165 (4) ◽  
pp. 1218-1223 ◽  
Author(s):  
V H Perry ◽  
M C Brown ◽  
S Gordon

Using mAbs and immunocytochemistry we have examined the response of macrophages (M phi) after crush injury to the sciatic or optic nerve in the mouse and rat. We have established that large numbers of M phi enter peripheral nerves containing degenerating axons; the M phi are localized to the portion containing damaged axons, and they phagocytose myelin. The period of recruitment of the M phi in the peripheral nerve is before and during the period of maximal proliferation of the Schwann cells. In contrast, the degenerating optic nerve attracts few M phi, and the removal of myelin is much slower. These results show the clearly different responses of M phi to damage in the central and peripheral nervous systems, and suggest that M phi may be an important component of subsequent repair as well as myelin degradation.


2006 ◽  
Vol 23 (12) ◽  
pp. 1883-1894 ◽  
Author(s):  
Olivier Alluin ◽  
François Feron ◽  
Christophe Desouches ◽  
Erick Dousset ◽  
Jean-François Pellissier ◽  
...  

Author(s):  
Samyak Pandey ◽  
Jayesh Mudgal

AbstractInjury to the peripheral nerve is traditionally referred to acquired nerve injury as they are the result of physical trauma due to laceration, stretch, crush and compression of nerves. However, peripheral nerve injury may not be completely limited to acquired physical trauma. Peripheral nerve injury equally implies clinical conditions like Guillain-Barré syndrome (GBS), Carpal tunnel syndrome, rheumatoid arthritis and diabetes. Physical trauma is commonly mono-neuropathic as it engages a single nerve and produces focal damage, while in the context of pathological conditions the damage is divergent involving a group of the nerve causing polyneuropathy. Damage to the peripheral nerve can cause a diverse range of manifestations from sensory impairment to loss of function with unpredictable recovery patterns. Presently no treatment option provides complete or functional recovery in nerve injury, as nerve cells are highly differentiated and inert to regeneration. However, the regenerative phenotypes in Schwann cells get expressed when a signalling cascade is triggered by neurotrophins. Neurotrophins are one of the promising biomolecules that are released naturally post-injury with the potential to exhibit better functional recovery. Pharmacological intervention modulating the expression of these neurotrophins such as brain-derived neurotrophic factor (BDNF) and pituitary adenylyl cyclase-activating peptide (PACAP) can prove to be a significant treatment option as endogenous compounds which may have remarkable innate advantage showing maximum ‘biological relevance’. Graphical abstract


2020 ◽  
Vol 40 (32) ◽  
pp. 6165-6176 ◽  
Author(s):  
Chelsey B. Reed ◽  
Luciana R. Frick ◽  
Adam Weaver ◽  
Mariapaola Sidoli ◽  
Elizabeth Schlant ◽  
...  

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