Immunohistochemical assessment of rat nerve isografts and immunosuppressed allografts

Hellenbrand, Daniel J.; Kaeppler, Katie E.; Ehlers, Mark; Thompson, C. Ray; Zurko, Joanna; Buchholz, Morgan M; Springer, Alexandra R; Thompson, Daniel L.; Ibrahim, Rami K; Hanna, Amgad S.

doi:10.1080/01616412.2016.1248626

Cited by 6 publications

(3 citation statements)

References 56 publications

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“…They have found better nerve regeneration in large-diameter nerve grafts than in small-diameter nerve grafts, whereas with regard to the length of the grafted nerve, short nerve allografts give higher axon counts than long ones, the same as with autografts [108]. Recently published data suggest that even though cyclosporin A is effective at reducing graft rejection, axon regeneration is still superior in autografts versus immunosuppressed allografts [109]. Furthermore, cyclosporin A effectively prevented postoperative epineurial fibrosis on rat sciatic nerves after peripheral nerve surgery with no adverse effects after topical application [102].…”

Section: Cyclosporin Amentioning

confidence: 98%

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

Mekaj¹

2017

Peripheral Nerve Regeneration - From Surgery to New Therapeutic Approaches Including Biomaterials and Cell-Based Therapies Deve

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Peripheral nerve injuries are frequent and represent a significant pathology of the peripheral nervous system because, despite operative techniques and successful microsurgical repair, in most cases, the nerve repair is followed by scar formation. Numerous investigations have been carried out with the aim of finding pharmacological substances that can prevent scar formation and speed up the regeneration of repaired nerves. This chapter is dedicated to the efforts of many researchers to find different pharmacological agents with local effects on the improvement of nerve regeneration. Numerous experiments have been carried out in mice and rabbits using hyaluronic acid, tacrolimus, cyclosporin A, melatonin, vitamin B12, methylprednisolone, riluzole and potassium and calcium channel blockers. In the experimental animal studies, topical pharmacological agents were used at the site of peripheral nerve repair. The effect of these substances is most commonly studied in sciatic nerve injury in experimental animals. Their effects were evaluated using a variety of methods, such as morphological, biomechanical, electrophysiological and functional evaluation, and the above-mentioned substances, have been shown to have neuroprotective and neuroregenerative properties though different mechanisms.

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Section: Cyclosporin Amentioning

confidence: 98%

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

Mekaj¹

2017

Peripheral Nerve Regeneration - From Surgery to New Therapeutic Approaches Including Biomaterials and Cell-Based Therapies Deve

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“…Established long-term rat allografts in immunocompromised or immunosuppressed hosts have been shown to be protected by normal permeability barriers, which were assumed to be from donor perineurium and endoneurial vasculature (Zalewski et al 1993). However, lymphocyte infiltration into nerve allografts through compromised barriers will occur in immunocompetent hosts (Gulati 1998;Hellenbrand et al 2016).…”

Section: The Immune Response To Peripheral Nerve Graftsmentioning

confidence: 99%

The Immune Response and Implications for Nerve Repair

Roberton

2021

Peripheral Nerve Tissue Engineering and Regeneration

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This chapter aims to provide an overview of the host response to allografts or tissue-engineered constructs containing allogeneic cells in peripheral nerve repair, and potential approaches for promoting the survival of nerve grafts. A large body of current research aims to improve surgical approaches for nerve repair beyond that of the autograft. Potential approaches include nerve allografts, or tissue-engineered nerve constructs which could provide an unlimited source of donor tissue for nerve injury repair. This field requires an interdisciplinary approach to the design of novel therapies, and consideration of the immune response to transplants should not be overlooked. There are many benefits of including living donor cells within transplanted nerve conduits which can improve axonal guidance, vascularization, and promote the release of growth factors to increase regeneration. It is most likely that donor cells or tissues will be of allogeneic origin, with associated implications for eliciting an immune response on transplantation. The following sections provide a summary of the immune response to nerve grafts for consideration in the development of approaches to nerve repair, including some approaches currently under investigation for preventing rejection of transplants.

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“… 18 Allogeneic nerve transplantation could be an ideal option to bridge long gaps in the injured nerve, but the paucity of basic information of the cellular mechanisms of rejection and standard preclinical studies identifying immunosuppressive regimens have hampered the development of nerve transplantation. 19 , 20 Some past attempts to understand the immunologic basis for rejection of allogeneic nerve transplants have been undertaken, but the comprehensive characterization of these cellular mechanisms remains understudied. 21 - 23 In addition, once a feasible model of allogeneic nerve transplantation has been established, a detailed understanding of the cellular mechanisms will assist in the identification of a suitable immunosuppressive therapy.…”

mentioning

confidence: 99%

Cellular Mechanisms of Rejection of Optic and Sciatic Nerve Transplants: An Observational Study

Yonar

Uehara

Banouni

et al. 2020

Transplantation Direct

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Background. Organ transplantation is a standard therapeutic strategy for irreversible organ damage, but the utility of nerve transplantation remains generally unexplored, despite its potential benefit to a large patient population. Here, we aimed to establish a feasible preclinical mouse model for understanding the cellular mechanisms behind the rejection of peripheral and optic nerves. Methods. We performed syngenic and allogenic transplantation of optic and sciatic nerves in mice by inserting the nerve grafts inside the kidney capsule, and we assessed the allografts for signs of rejection through 14 d following transplantation. Then, we assessed the efficacy of CTLA4 Ig, Rapamycin, and anti-CD3 antibody in suppressing immune cell infiltration of the nerve allografts. Results. By 3 d posttransplantation, both sciatic and optic nerves transplanted from BALB/c mice into C57BL/6J recipients contained immune cell infiltrates, which included more CD11b+ macrophages than CD3+ T cells or B220+ B cells. Ex vivo immunogenicity assays demonstrated that sciatic nerves demonstrated higher alloreactivity in comparison with optic nerves. Interestingly, optic nerves contained higher populations of anti-inflammatory PD-L1+ cells than sciatic nerves. Treatment with anti-CD3 antibody reduced immune cell infiltrates in the optic nerve allograft, but exerted no significant effect in the sciatic nerve allograft. Conclusions. These findings establish the feasibility of a preclinical allogenic nerve transplantation model and provide the basis for future testing of directed, high-intensity immunosuppression in these mice.

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Immunohistochemical assessment of rat nerve isografts and immunosuppressed allografts

Abstract: Autografts have long been the gold standard for treating major nerve injuries and these data suggest that even though CSA is effective at reducing graft rejection, axon regeneration is still superior in autografts versus immunosuppressed allografts.

Cited by 6 publications

References 56 publications

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

The Immune Response and Implications for Nerve Repair

Cellular Mechanisms of Rejection of Optic and Sciatic Nerve Transplants: An Observational Study

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