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Biofabrication Sep 2022Electroceuticals provide promising opportunities for peripheral nerve regeneration, in terms of modulating the extensive endogenous tissue repair mechanisms between... (Review)
Review
Electroceuticals provide promising opportunities for peripheral nerve regeneration, in terms of modulating the extensive endogenous tissue repair mechanisms between neural cell body, axons and target muscles. However, great challenges remain to deliver effective and controllable electroceuticals via bioelectronic implantable device. In this review, the modern fabrication methods of bioelectronic conduit for bridging critical nerve gaps after nerve injury are summarized, with regard to conductive materials and core manufacturing process. In addition, to deliver versatile electrical stimulation, the integration of implantable bioelectronic device is discussed, including wireless energy harvesters, actuators and sensors. Moreover, a comprehensive insight of beneficial mechanisms is presented, including up-to-dateand clinical evidence. By integrating conductive biomaterials, 3D engineering manufacturing process and bioelectronic platform to deliver versatile electroceuticals, the modern biofabrication enables comprehensive biomimetic therapies for neural tissue engineering and regeneration in the new era.
Topics: Biocompatible Materials; Nerve Regeneration; Nerve Tissue; Peripheral Nerves; Tissue Engineering
PubMed: 35995036
DOI: 10.1088/1758-5090/ac8baa -
Disease Models & Mechanisms Jan 2023The peripheral nervous system plays an important role in cancer progression. Studies in multiple cancer types have shown that higher intratumoral nerve density is... (Review)
Review
The peripheral nervous system plays an important role in cancer progression. Studies in multiple cancer types have shown that higher intratumoral nerve density is associated with poor outcomes. Peripheral nerves have been shown to directly regulate tumor cell properties, such as growth and metastasis, as well as affect the local environment by modulating angiogenesis and the immune system. In this Review, we discuss the identity of nerves in organs in the periphery where solid tumors grow, the known mechanisms by which nerve density increases in tumors, and the effects these nerves have on cancer progression. We also discuss the strengths and weaknesses of current in vitro and in vivo models used to study nerve-cancer interactions. Increased understanding of the mechanisms by which nerves impact tumor progression and the development of new approaches to study nerve-cancer interactions will facilitate the discovery of novel treatment strategies to treat cancer by targeting nerves.
Topics: Humans; Neoplasms; Nerve Tissue
PubMed: 36621886
DOI: 10.1242/dmm.049729 -
Cells Dec 2021Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian,...
Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular-nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics.
Topics: Animals; Cystadenocarcinoma, Serous; Disease Models, Animal; Female; Ganglia, Spinal; Mice, Inbred C57BL; Nerve Tissue; Ovarian Neoplasms; PTEN Phosphohydrolase; Sensory Receptor Cells; Tumor Suppressor Protein p53; Ultrasonography; Mice
PubMed: 34944001
DOI: 10.3390/cells10123491 -
Muscle & Nerve Aug 2021After initial investigation of patients presenting with symptoms suggestive of neuropathy, a clinical decision is made for a minority of patients to undergo further... (Review)
Review
After initial investigation of patients presenting with symptoms suggestive of neuropathy, a clinical decision is made for a minority of patients to undergo further assessment with nerve biopsy. Many nerve biopsies do not demonstrate a definitive pathological diagnosis and there is considerable cost and morbidity associated with the procedure. This highlights the need for appropriate selection of patients, nerves and neuropathology techniques. Additionally, concomitant muscle and skin biopsies may improve the diagnostic yield in some cases. Several advances have been made in diagnostics in recent years, particularly in genomics. The indications for nerve biopsy have consequently changed over time. This review explores the current indications for nerve biopsies and some of the issues surrounding its use. Also included are comments on alternative diagnostic modalities that may help to supplant or reduce the use of nerve biopsy as a diagnostic test. These primarily include extraneural biopsy and neuroimaging techniques such as magnetic resonance neurography and nerve ultrasound. Finally, we propose an algorithm to assist in deciding when to perform nerve biopsies.
Topics: Humans; Muscle, Skeletal; Nerve Tissue; Neurosurgical Procedures; Peripheral Nervous System Diseases; Skin; Sural Nerve
PubMed: 33629393
DOI: 10.1002/mus.27201 -
Nature Communications Dec 2022The role of non-neuronal glial cells in the regulation of adipose sympathetic nerve activity and adipocyte functions such as white adipose tissue lipid lipolysis is...
The role of non-neuronal glial cells in the regulation of adipose sympathetic nerve activity and adipocyte functions such as white adipose tissue lipid lipolysis is poorly understood. Here, we combine chemo/optogenetic manipulations of medio-basal hypothalamic astrocytes, real-time fiber photometry monitoring of white adipose tissue norepinephrine (NE) contents and nerve activities, electrophysiological recordings of local sympathetic inputs to inguinal white adipose tissue (iWAT), and adipose tissue lipid lipolytic assays to define the functional roles of hypothalamic astrocytes in the regulation of iWAT sympathetic outflow and lipolysis. Our results show that astrocyte stimulation elevates iWAT NE contents, excites sympathetic neural inputs and promotes lipolysis. Mechanistically, we find that sympathetic paravertebral ganglia (PG) partake in those astrocyte effects. We also find that astrocyte stimulation excites pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH), and chemogenetic inhibition of POMC neurons blunts the effects induced by astrocyte stimulation. While we cannot exclude potential roles played by other cell populations such as microglia, our findings in this study reveal a central astrocyte-peripheral adipocyte axis modulating sympathetic drive to adipose tissues and adipocyte functions, one that might serve as a target for therapeutic intervention in the treatment of obesity.
Topics: Mice; Animals; Adipocytes, White; Nerve Tissue; Lipids
PubMed: 36477150
DOI: 10.1038/s41467-022-35258-6 -
International Journal of Molecular... Mar 2021Regardless of the nerve defect length, nerve injury is a debilitating condition for the affected patient that results in loss of sensory and motor function. These... (Review)
Review
Regardless of the nerve defect length, nerve injury is a debilitating condition for the affected patient that results in loss of sensory and motor function. These functional impairments can have a profound impact on the patient's quality of life. Surgical approaches for the treatment of short segment nerve defects are well-established. Autologous nerve transplantation, considered the gold standard, and the use of artificial nerve grafts are safe and successful procedures for short segment nerve defect reconstruction. Long segment nerve defects which extend 3.0 cm or more are more problematic for repair. Methods for reconstruction of long defects are limited. Artificial nerve grafts often fail to regenerate and autologous nerve grafts are limited in length and number. Cadaveric processed/unprocessed nerve allografts are a promising alternative in nerve surgery. This review gives a systematic overview on pre-clinical and clinical approaches in nerve allograft transplantation.
Topics: Humans; Nerve Tissue; Peripheral Nerve Injuries; Transplantation, Homologous
PubMed: 33805321
DOI: 10.3390/ijms22073515 -
Current Opinion in Biotechnology Dec 2021Neural implants enable bidirectional communications with nervous tissue and have demonstrated tremendous potential in research and clinical applications. To obtain high... (Review)
Review
Neural implants enable bidirectional communications with nervous tissue and have demonstrated tremendous potential in research and clinical applications. To obtain high fidelity and stable information exchange, we need to minimize the undesired host responses and achieve intimate neuron-device interaction. This paper highlights the key bio-integrative strategies aimed at seamless integration through intelligent device designs to minimize the immune responses, as well as incorporate bioactive elements to actively modulate cellular reactions. These approaches span from surface modification and bioactive agent delivery, to biomorphic and biohybrid designs. Many of these strategies have shown effectiveness in functional outcome measures, others are exploratory but with fascinating potentials. The combination of bio-integrative strategies may synergistically promote the next generation of neural interfaces.
Topics: Nerve Tissue; Neurons; Prostheses and Implants
PubMed: 34710753
DOI: 10.1016/j.copbio.2021.10.003 -
Theranostics 2023Severe injuries or diseases affecting the peripheral and central nervous systems can result in impaired organ function and permanent paralysis. Conventional... (Review)
Review
Severe injuries or diseases affecting the peripheral and central nervous systems can result in impaired organ function and permanent paralysis. Conventional interventions, such as drug administration and cell-based therapy, exhibit limited effectiveness due to their inability to preserve post-implantation cell survival and impede the deterioration of adjacent tissues. Exosomes have recently emerged as powerful tools for tissue repair owing to their proteins and nucleic acids, as well as their unique phospholipid properties, which facilitate targeted delivery to recipient cells. Engineering exosomes, obtained by manipulating the parental cells or directly functionalizing exosomes, play critical roles in enhancing regenerative repair, reducing inflammation, and maintaining physiological homeostasis. Furthermore, exosomes have been shown to restore neurological function when used in combination with biomaterials. This paper primarily focuses on the engineering strategies and delivery routes of exosomes related to neural research and emphasizes the theranostic application of optimized exosomes in peripheral nerve, traumatic spinal cord, and brain injuries. Finally, the prospects of exosomes development and their combination with other approaches will be discussed to enhance our knowledge on their theranostic effectiveness in neurological diseases.
Topics: Exosomes; Precision Medicine; Cell- and Tissue-Based Therapy; Nerve Tissue; Biocompatible Materials; Tissue Engineering
PubMed: 37554270
DOI: 10.7150/thno.84971 -
Acta Biomaterialia Mar 2017Unlike other tissue types, like epithelial tissue, which consist of cells with a much more homogeneous structure and function, the nervous tissue spans in a complex... (Review)
Review
UNLABELLED
Unlike other tissue types, like epithelial tissue, which consist of cells with a much more homogeneous structure and function, the nervous tissue spans in a complex multilayer environment whose topographical features display a large spectrum of morphologies and size scales. Traditional cell cultures, which are based on two-dimensional cell-adhesive culture dishes or coverslips, are lacking topographical cues and mainly simulate the biochemical microenvironment of the cells. With the emergence of micro- and nano-fabrication techniques new types of cell culture platforms are developed, where the effect of various topographical cues on cellular morphology, proliferation and differentiation can be studied. Different approaches (regarding the material, fabrication technique, topographical characteristics, etc.) have been implemented. The present review paper aims at reviewing the existing body of literature on the use of artificial micro- and nano-topographical features to control neuronal and neuroglial cells' morphology, outgrowth and neural network topology. The cell responses-from phenomenology to investigation of the underlying mechanisms- on the different topographies, including both deterministic and random ones, are summarized.
STATEMENT OF SIGNIFICANCE
There is increasing evidence that physical cues, such as topography, can have a significant impact on the neural cell functions. With the aid of micro-and nanofabrication techniques, new types of cell culture platforms are developed and the effect of surface topography on the cells has been studied. The present review article aims at reviewing the existing body of literature reporting on the use of various topographies to study and control the morphology and functions of cells from nervous tissue, i.e. the neuronal and the neuroglial cells. The cell responses-from phenomenology to investigation of the underlying mechanisms- on the different topographies, including both deterministic and random ones, are summarized.
Topics: Animals; Biocompatible Materials; Cell Shape; Humans; Nerve Tissue; Neurites; Neuroglia; Surface Properties
PubMed: 28069509
DOI: 10.1016/j.actbio.2017.01.023 -
Cell Stem Cell Sep 2021Epidermal stem cells display remarkable capacities to restore the barrier upon skin injury. In this issue of Cell Stem Cell, Huang et al. (2021) use innovative...
Epidermal stem cells display remarkable capacities to restore the barrier upon skin injury. In this issue of Cell Stem Cell, Huang et al. (2021) use innovative high-resolution intravital imaging to identify a vital function of sensory nerves in regulating a subset of epidermal stem cells for wound repair.
Topics: Epidermal Cells; Nerve Tissue; Stem Cells; Wound Healing
PubMed: 34478625
DOI: 10.1016/j.stem.2021.08.009