Nerve Regeneration

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Chengbin Xue - One of the best experts on this subject based on the ideXlab platform.

  • Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.
    Frontiers in cellular neuroscience, 2017
    Co-Authors: Hongkui Wang, Qi Guo, Hui Zhu, Ping Zhang, Tianmei Qian, Chengbin Xue
    Abstract:

    Peripheral nervous system owns the ability of self-Regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue Regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral Nerve Regeneration and angiogenesis post peripheral Nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic Nerve transection in SD rats. Nerve Regeneration and angiogenesis were activated at 1 day immediately after sciatic Nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both Nerve Regeneration and angiogenesis after sciatic Nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both Nerve Regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of Nerve Regeneration and angiogenesis simultaneously response to sciatic Nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral Nerve Regeneration and angiogenesis after peripheral Nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define Nerve injury-induced micro-environmental variation for achieving desired peripheral Nerve Regeneration.

  • Stem Cell and Peripheral Nerve Regeneration
    Translational Medicine Research, 2015
    Co-Authors: Chengbin Xue
    Abstract:

    The application of stem cells has always attracted great interest in the field of peripheral Nerve Regeneration. In recent years, the rapid development of neural tissue engineering makes it possible to use stem cell transplantation to repair peripheral Nerve injury. Seed/support cell or cellular source from stem cell has been known as one of the components for neural tissue engineering. The tissue-engineered Nerve grafts (TENGs) support the Regeneration of longer peripheral Nerve gaps than scaffold alone. A number of TENGs have been used experimentally to bridge long peripheral Nerve gaps in various animal models, where the desired outcome is peripheral Nerve Regeneration and functional recovery. Stem cells may improve the local microenvironment in Nerve injury sites, providing necessary conditions for axonal Regeneration. Nowadays, the types of stem cells and their application tend to diversify. Stem cells are more effective in providing necessary factors that promote peripheral Nerve Regeneration. So far, the application of stem cells for peripheral Nerve Regeneration is limited mainly because of the low survival rate of transplanted stem cells due to host immune rejection and changes in the local microenvironment. Here, we summarize the latest research progress and application strategies of stem cells in peripheral Nerve Regeneration. To push the translation of stem cell application for peripheral Nerve Regeneration into the clinic, we anticipate that a TENG with a close proximity to the regenerative microenvironment of the peripheral nervous system (PNS) will be developed.

Simon P. Frostick - One of the best experts on this subject based on the ideXlab platform.

  • Peripheral Nerve Regeneration
    European Surgery, 2005
    Co-Authors: Vishal Sahni, Simon P. Frostick
    Abstract:

    BACKGROUND: Understanding of the mechanisms underlying peripheral Nerve Regeneration represents a prerequisite for adequate design for treatment of injured peripheral Nerves. METHODS: Review of recent literature on mechanisms underlying peripheral Nerve Regeneration. RESULTS: Peripheral Nerve Regeneration is orchestrated by mechanisms involving Nerve, muscle, connective tissue and immune cells and mediators released from these cells (growth factors, interleukins, glycoproteins). Success of peripheral Nerve repair depends on patient's age, time from injury, site and extent of Nerve lesion (proximal vs. distal). Future studies will evaluate the impact of novel approaches including stem cells, growth factors and extracellular matrix glycoproteins (fibronectin, laminin). CONCLUSIONS: Peripheral Nerve Regeneration involves complex mechanisms, the understanding of which will profoundly aid treatment design.

  • Neurotrophin‐4 delivered by fibrin glue promotes peripheral Nerve Regeneration
    Muscle & Nerve, 2001
    Co-Authors: Qi Yin, Graham J. Kemp, Simon C. Wagstaff, Simon P. Frostick
    Abstract:

    Neurotrophin-4 (NT-4) is a recently identified neurotrophic factor with potential trophic effects on subpopulations of neurons. Little is known about its role in peripheral Nerve Regeneration following Nerve injury. To investigate this, 48 Sprague-Dawley rats underwent left sciatic Nerve transection and immediate repair. Fibrin glue mixed with either NT-4 or vehicle (control) was injected around the Nerve repair site. Nerve Regeneration was assessed both functionally and histomorphometrically. The results showed that the NT-4-treated group had a significant increase compared with the control in the Regeneration distance at 5 days. The sciatic function index was significantly greater in the NT-4 group from 40 to 60 days after Nerve repair. Morphometric analysis revealed that Nerves treated with NT-4 had significant improvement in the number of regenerated axons, axonal diameter, and myelin thickness. These results suggest that NT-4 is a potent factor improving rat sciatic Nerve Regeneration.

  • Neurotrophins, neurones and peripheral Nerve Regeneration
    Journal of Hand Surgery (European Volume), 1998
    Co-Authors: Graham J. Kemp, Simon P. Frostick
    Abstract:

    Successful peripheral Nerve Regeneration requires optimal conditions both in the macro-environment and micro-environment. Many methods have been used to improve the macro-environment for the regenerating Nerve. However, much less is known about the micro-environment, and in particular the complex neurochemical interactions involved. Several neurotrophic factors have been shown to play an essential trophic role in the development, maintenance and regulation of neuronal function. These include Nerve growth factor (NGF) and several recently identified members of the NGF family, namely brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5) and neurotrophin-6 (NT-6). In this review we summarize recent studies of the effects of these neurotrophins on neurones, especially their effects on motor neurones and their axonal outgrowth. We discuss prospects for the future and point out what remains to be understood about the role of neurotrophins to enhance peripheral Nerve Regeneration.

Gregory R. D. Evans - One of the best experts on this subject based on the ideXlab platform.

  • Strategic sequences" in adipose-derived stem cell Nerve Regeneration.
    Microsurgery, 2013
    Co-Authors: Alan D. Widgerow, Ara A. Salibian, Emil Kohan, Tadeu Sartiniferreira, Hassaan Afzel, Thanh Tham, Gregory R. D. Evans
    Abstract:

    Background: Peripheral Nerve injuries (PNI) are a major source of morbidity worldwide. The development of cellular regenerative therapies has the potential to improve outcomes of Nerve injuries. However, an ideal therapy has yet to be found. The purpose of this study is to examine the current literature key points of regenerative techniques using human adipose-derived stem cells (hADSCs) for Nerve Regeneration and derive a comprehensive approach to hADSC therapy for PNI. Methods: A literature review was conducted using the electronic database PubMed to search for current experimental approaches to repairing PNI using hADSCs. Key search elements focused on specific components of Nerve Regeneration paradigms, including (1) support cells, (2) scaffolds, and (3) Nerve conduits. Results: Strategic sequences were developed by optimizing the components of different experimental regenerative therapies. These sequences focus on priming hADSCs within a specialized growth medium, a hydrogel matrix base, and a collagen Nerve conduit to achieve neuromodulatory Nerve Regeneration. hADSCs may exert their neuroregenerative influence through paracrine effects on surrounding Schwann cells in addition to physical interactions with injured tissue. Conclusions: hADSCs may play a key role in Nerve Regeneration by acting primarily as support for local neurotrophic mediation and modulation of Nerve growth rather than that of a primary neuronal differentiation agent. V C 2013 Wiley Periodicals, Inc. Microsurgery 00:000‐000, 2013. The standard method of treatment of peripheral Nerve injuries (PNI) with autologous Nerve grafts has limitations, including donor site morbidity and suboptimal functional recovery. Tissue engineering provides an interesting alternative to current treatments and several variations of therapies have been studied, including Nerve conduits, regenerative stimulants, and cellular components. However, intervening to change the natural physiologic course at this level requires a proper understanding of the timing and mechanisms of the events that occur during degeneration and regrowth after PNI. Nerve injury is accompanied by a sequence of events that precede the final outcome of Nerve healing. 1 This outcome ranges from almost complete Nerve Regeneration to degeneration, Nerve loss, neuroma formation, and incomplete or absent Nerve Regeneration. Each sequence within this Nerve injury process is accompanied by biologic events that may influence the ongoing regenerative process. Thus, any strategy relating to Nerve Regeneration should consider these sequences individually and cumulatively as the process of Regeneration unfolds. From this standpoint, it is pertinent to deconstruct PNI into sequences relating to degeneration, initial Regeneration, and possible intervention strategies that may limit, speed up, or facilitate such sequences. This approach enables us to examine the process at different time frames and to plan combined approaches that consider most of these components when designing a comprehensive regenerative device. Human adipose tissue-derived stem cells (hADSCs) are a heterogeneous group of multipotent progenitor cells that can be harvested autogenously in high numbers with low donor site morbidity and have been used in several studies to promote Nerve Regeneration. 2‐6 This review focuses on the utilization of hADSCs as neurotrophic mediators, stimulating Nerve Regeneration from environmental cues rather than promoting the in vitro neuronal differentiation of hADSCs. The goal of this approach is to create an effective method of promoting Nerve Regeneration while minimizing the manipulation of autologous cells to move toward a transnational therapy.

  • Neuromodulatory Nerve Regeneration: adipose tissue-derived stem cells and neurotrophic mediation in peripheral Nerve Regeneration.
    Journal of neuroscience research, 2013
    Co-Authors: Alan D. Widgerow, Ara A. Salibian, Shadi Lalezari, Gregory R. D. Evans
    Abstract:

    Peripheral Nerve injury requiring Nerve gap reconstruction remains a major problem. In the quest to find an alternative to autogenous Nerve graft procedures, attempts have been made to differentiate mesenchymal stem cells into neuronal lineages in vitro and utilize these cellular constructs for Nerve Regeneration. Unfortunately, this has produced mixed results, with no definitive procedure matching or surpassing traditional Nerve grafting procedures. This review presents a different approach to Nerve Regeneration. The literature was reviewed to evaluate current methods of using adipose-derived stem cells (ADSCs) for peripheral Nerve Regeneration in in vivo models of animal peripheral Nerve injury. The authors present cited evidence for directing Nerve Regeneration through paracrine effects of ADSCs rather than through in vitro Nerve Regeneration. The paracrine effects rely mainly, but not solely, on the elaboration of Nerve growth factors and neurotrophic mediators that influence surrounding host cells to orchestrate in vivo Nerve Regeneration. Although this paradigm has been indirectly referred to in a host of publications, few major efforts for this type of neuromodulatory Nerve Regeneration have been forthcoming. The ADSCs are initially “primed” in vitro using specialized controlled medium (not for neuronal differentiation but for sustainability) and then incorporated into a hydrogel base matrix designed for this purpose. This core matrix is then introduced into a natural collagen-based Nerve conduit. The prototype design concepts, evidence for paracrine influences, and regulatory hurdles that are avoided using this approach are discussed. V C 2013 Wiley Periodicals, Inc.

Shelly E. Sakiyama-elbert - One of the best experts on this subject based on the ideXlab platform.

  • Matrices, scaffolds & carriers for cell delivery in Nerve Regeneration.
    Experimental neurology, 2018
    Co-Authors: Ze Zhong Wang, Shelly E. Sakiyama-elbert
    Abstract:

    Nerve injuries can be life-long debilitating traumas that severely impact patients' quality of life. While many acellular neural scaffolds have been developed to aid the process of Nerve Regeneration, complete functional recovery is still very difficult to achieve, especially for long-gap peripheral Nerve injury and most cases of spinal cord injury. Cell-based therapies have shown many promising results for improving Nerve Regeneration. With recent advances in neural tissue engineering, the integration of biomaterial scaffolds and cell transplantation are emerging as a more promising approach to enhance Nerve Regeneration. This review provides an overview of important considerations for designing cell-carrier biomaterial scaffolds. It also discusses current biomaterials used for scaffolds that provide permissive and instructive microenvironments for improved cell transplantation.

  • Controlled release of Nerve growth factor enhances sciatic Nerve Regeneration
    Exp Neurol, 2003
    Co-Authors: A C Lee, V M Yu, J B Lowe 3rd, D A Hunter, M. J. Brenner, Susan E. Mackinnon, Shelly E. Sakiyama-elbert
    Abstract:

    Based on previous studies demonstrating the potential of growth factors to enhance peripheral Nerve Regeneration, we developed a novel growth factor delivery system to provide sustained delivery of Nerve growth factor (NGF). This delivery system uses heparin to immobilize NGF and slow its diffusion from a fibrin matrix. This system has been previously shown to enhance neurite outgrowth in vitro, and in this study, we evaluated the ability of this delivery system to enhance Nerve Regeneration through conduits. We tested the effect of controlled NGF delivery on peripheral Nerve Regeneration in a 13-mm rat sciatic Nerve defect. The heparin-containing delivery system was studied in combination with three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with positive controls (isografts) and negative controls (fibrin alone, NGF alone, and empty conduits). Nerves were harvested at 6 weeks postoperatively for histomorphometric analysis. Axonal Regeneration in the delivery system groups revealed a marked dose-dependent effect. The total number of Nerve fibers at both the mid-conduit level and in the distal Nerve showed no statistical difference for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The results of this study demonstrate that the incorporation of a novel delivery system providing controlled release of growth factors enhances peripheral Nerve Regeneration and represents a significant contribution toward enhancing Nerve Regeneration across short Nerve gaps.

  • Bioactive delivery systems for Nerve Regeneration
    Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and, 2002
    Co-Authors: Shelly E. Sakiyama-elbert
    Abstract:

    The goal of this research is to develop drug delivery systems that can be controlled by cellular activity during Nerve Regeneration. We utilize heparin-binding affinity to sequester growth factors within heparin-containing fibrin matrices. These affinity-immobilized growth factors can be released based on active, cellular degradation of the matrix rather than by passive, diffusion-based release and allow us to control growth factor delivery over the entire time course of tissue Regeneration. This approach to bioactive delivery has been shown to promote Nerve Regeneration comparable to Nerve allograft in rat sciatic Nerve transection models.

Hongkui Wang - One of the best experts on this subject based on the ideXlab platform.

  • Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.
    Frontiers in cellular neuroscience, 2017
    Co-Authors: Hongkui Wang, Qi Guo, Hui Zhu, Ping Zhang, Tianmei Qian, Chengbin Xue
    Abstract:

    Peripheral nervous system owns the ability of self-Regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue Regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral Nerve Regeneration and angiogenesis post peripheral Nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic Nerve transection in SD rats. Nerve Regeneration and angiogenesis were activated at 1 day immediately after sciatic Nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both Nerve Regeneration and angiogenesis after sciatic Nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both Nerve Regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of Nerve Regeneration and angiogenesis simultaneously response to sciatic Nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral Nerve Regeneration and angiogenesis after peripheral Nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define Nerve injury-induced micro-environmental variation for achieving desired peripheral Nerve Regeneration.