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Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study

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World Journal of Stem Cells 2024年第1期16卷 19-32页

作者： ErdinçCivelek Serdar Kabatas Eyüp Can Savrunlu Furkan Diren Necati Kaplan Demet Ofluoğlu Erdal Karaöz Department of Neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyGaziosmanpaşa 34255IstanbulTurkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalÇorlu 59860TekirdağTurkey Department of Physical Medicine and Rehabilitation Ofluoğlu KlinikGöztepe 34728IstanbulTurkey Liv Hospital Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell)Beşiktaş34340IstanbulTurkey Department of Histology and Embryology Istinye UniversityFaculty of MedicineZeytinburnu 34010IstanbulTurkey Istinye University Center for Stem Cell and Tissue Engineering Research and PracticeBeşiktaş34340IstanbulTurkey

BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.AIM To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.METHODS A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife assault.The cut is located on the left arm,specifically below the elbow.The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage.The sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion microvesicles.This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway.The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.RESULTS The duration of the patient’s follow-up period was 180 d.An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting.Upon the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve.This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale.The results indicated that the level of improvement in motor function was classified as M5,denoting an excellent outcome.Additionally,the level of improvement in sensory function was classified as S3+,indicating a good outcome.It is noteworthy that these assessments were conducte

关键词： Mesenchymal stem cell Exosomes Radial nerve sural nerve

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Autologous transplantation with fewer fibers repairs large peripheral nerve defects

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Neural Regeneration Research 2017年第12期12卷 2077-2083页

作者： Jiu-xu Deng Dian-yin Zhang Ming Li Jian Weng Yu-hui Kou Pei-xun Zhang Na Han Bo Chen Xiao-feng Yin Bao-guo Jiang Department of Orthopedics and Trauma Peking University People's Hospital Beijing China

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves（10–30 mm long） were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification＇ phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect.

关键词： nerve regeneration peripheral nerve injury peripheral nerve defect autologous nerve graft functional recovery nerve conductionvelocity sural nerve common peroneal nerve sleeve bridging suture neural regeneration

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Preparation of human decellularized peripheral nerve allograft using amphoteric detergent and nuclease

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Neural Regeneration Research 2021年第9期16卷 1890-1896页

作者： Joo-Yul Bae Suk Young Park Young Ho Shin Shin Woo Choi Jae Kwang Kim Department of Orthopedic Surgery University of Ulsan College of MedicineGangneung Asan HospitalGangneung-siKorea Department of Orthopedic Surgery University of Ulsan College of MedicineAsan Medical CenterSeoulKorea

Animal studies have shown that amphoteric detergent and nuclease(DNase I and ribonuclease A) is the most reliable decellularization method of the peripheral nerve. However, the optimal combination of chemical reagents for decellularization of human nerve allograft needs further investigation. To find the optimal protocol to remove the immunogenic cellular components of the nerve tissue and preserve the basal lamina and extracellular matrix and whether the optimal protocol can be applied to larger-diameter human peripheral nerves, in this study, we decellularized the median and sural nerves from the cadavers with two different methods: nonionic and anionic detergents(Triton X-100 and sodium deoxycholate) and amphoteric detergent and nuclease(3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate(CHAPS), deoxyribonuclease I, and ribonuclease A). All cellular components were successfully removed from the median and sural nerves by amphoteric detergent and nuclease. Not all cellular components were removed from the median nerve by nonionic and anionic detergent. Both median and sural nerves treated with amphoteric detergent and nuclease maintained a completely intact extracellular matrix. Treatment with nonionic and anionic detergent decreased collagen content in both median and sural nerves, while the amphoteric detergent and nuclease treatment did not reduce collagen content. In addition, a contact cytotoxicity assay revealed that the nerves decellularized by amphoteric detergent and nuclease was biocompatible. Strength failure testing demonstrated that the biomechanical properties of nerves decellularized with amphoteric detergent and nuclease were comparable to those of fresh controls. Decellularization with amphoteric detergent and nuclease better remove cellular components and better preserve extracellular matrix than decellularization with nonionic and anionic detergents, even in large-diameter human peripheral nerves. In Korea, cadaveric studies are not yet legally subject to Institutional Review Board rev

关键词： median nerve sural nerve nuclease detergent human decellularized nerve graft

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Natural history of sensory nerve recovery after cutaneous nerve injury following foot and ankle surgery

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Neural Regeneration Research 2015年第1期10卷 99-103页

作者： Lu Bai Yan-ni Han Wen-tao Zhang Wei Huang Hong-lei Zhang Department of Sports Medicine Shenzhen Hospital of Peking University Department of Medical Ultrasonics Shenzhen Hospital of Peking University

Cutaneous nerve injury is the most common complication following foot and ankle surgery. However, clinical studies including long-term follow-up data after cutaneous nerve injury of the foot and ankle are lacking. In the current retrospective study, we analyzed the clinical data of 279 patients who underwent foot and ankle surgery. Subjects who suffered from apparent paresthesia in the cutaneous sensory nerve area after surgery were included in the study. Pa- tients received oral vitamin B^2 and methylcobalamin. We examined final follow-up data of 17 patients, including seven with sural nerve injury, five with superficial peroneal nerve injury, and five with plantar medial cutaneous nerve injury. We assessed nerve sensory function using the Medical Research Council Scale. Follow-up immediately, at 6 weeks, 3, 6 and 9 months, and 1 year after surgery demonstrated that sensory function was gradually restored in most patients within 6 months. However, recovery was slow at 9 months. There was no significant difference in sensory function between 9 months and 1 year after surgery. Painful neuromas occurred in four patients at 9 months to 1 year. The results demonstrated that the recovery of sensory func- tion in patients with various cutaneous nerve injuries after foot and ankle surgery required at least 6 months.

关键词： nerve regeneration natural history cutaneous nerve injury foot and ankle sural nerve superficial peroneal nerve medial plantar nerve neurosensory function neural regeneration

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Versatility of Reverse sural Fasciocutaneous Flap for Reconstruction of Distal Lower Limb Soft tissue Defects

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2014年第3期34卷 382-386页

作者：潘海涛郑启新杨述华吴斌刘建湘 Department of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology

Summary： In this study we present our experiences with the reverse sural fasciocutaneous flap to reconstruct the distal lower limb soft tissue defects caused by traumatic injuries. These flap graftings were carried out from Oct. 2010 to Dec. 2012 in our department. The series consisted of 36 patients, including 21 men and 15 women with an average age of 46.2 years （14-83 years） and with a medium followp period of 18 months （12-24 months）. Of all the cases of acute trauma, there were 10 eases of trauma of distal tibia, 9 cases of trauma of perimalleolus, and 17 cases of trauma of midfoot and forefoot. Related risk factors in the patients were diabetes （2 cases）, advanced age （〉65 years, 3 cases） and ciga- rette smoking （6 cases）. The reverse flow sural island flap irrigation depended on lower perforators of the peroneal artery. The fasciocutaneous pedicle was 3-4 cm in width and the anatomical structures consisted of the superficial and deep fascia, the sural nerve, short saphenous vein, superficial sural artery together with an islet of subcutaneous cellular tissue and skin. The most proximal border of the flap was only 1.5 cm away from the popliteal skin crease and the pivot point was 5-7 cm above the tip of the lateral malleolus. All the flaps survived. No arterial crisis occurred in any case. The venous congestion occurred in 2 cases and got better after raising the limbs and bloodletting. Only in an old man, 1.5 cm necrosis of distal margin of his flap occurred and finally healed after continuous dressing change. One-stage skin grafting was performed, and all the donor sites were sutured and successfully healed. It was concluded that the reverse sural fasciocutaneous flap is safe and reliable to extend to the proximal third even near the popliteal skin crease. We also concluded this flap can be safely and efficiently used to treat patients with large and far soft-tissue defects from the distal leg to the forefoot with more versatility and it is easier to reach the recipient sites.

关键词： sural nerve reverse island flap distal lower limb soft tissue defects

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TYPES　OF　CONVERGENT　NEURONS　OF　DORSAL　HORN　IN　THE　SPINAL　CORD　FROM　SOMATIC　AND　VISCERAL　INPUTS　IN　SPINAL　RATS

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Journal of Pharmaceutical Analysis 1995年第1期9卷 25-28页

作者： Zhu Zhongliang Jiang Sainan Niu HanZhang(Department of Physiology,Xi’an Medical University,Xi’an 710061)

The technique of stretching urinary bladder of rats was applied in order to analyze thedorsal horn convergent neurons from somatic and visceral inputs.A sundered and fifty-seven neurons were found in the dorsal horns,and LTM, WDR,NS was distinguished.Their numbers were 58(36.94%),86(54.78%),and 13(8.28%)respectively.Thirty-two of them were somatic-visceralcouvergent neurons(SVCN).The Physiological characteristics of SVCN,suck as latentes,numbersof spikes,conductive velocities from somatic and visceral inputs as well as receptive fields were studied.The SVCN in the experiment were classfied into 2 subgroups according to the their differentphysiological features: AC-V,C-V.All of the recorded SVCN were involved in C fibers.It indicatesthat SVCN play an important role in modulating senses,especially sense of pain.

关键词： sural nerve urinary bladder spinal cord convergent neuron

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The mechanisms underlying that injury of skin afferents does not produce neuropathic pain:the role of BDNF

The mechanisms underlying that injury of skin afferents does...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Li-Jun ZHOU Wen-Jie REN Yi ZHONG Tao YANG Xian-Guo LIU~(1 *) Pain Research Center and Department of Physiology Zhongshan Medicine School of Sun Yat-sen University Guangzhou 510089 China

＜正＞Objective Although a large body of evidence has shown that peripheral nerve injury usually induces neuropathic pain,there are also clinical studies demonstrating that injury of the sural nerve,which mainly innervates skin,fails to do so.The underlying mechanism,however,is largely unknown.Brain-derived neurotrophic factor（BDNF）,which is essential for late-phase LTP（L-LTP） in hippocampus,plays an important role in sensory neurotransmission in nociceptive pathways at both spinal and supraspinal levels.Our recent work has demonstrated that BDNF is critical for spinal L-LTP of C-fiber evoked field potentials.In the present study,we investigated whether electrical stimulation or injury of the tibial nerve,innervating both muscle and skin or the sural nerve,innervating mainly skin has different effects on producing neuropathic pain and on inducing LTP of C-fiber-evoked field potentials in spinal dorsal horn.The role of BDNF in the spinal LTP induced by electrical stimulation of the tibial nerve or the sural nerve was evaluated.Methods Pain behavior test,field potential recorded by electrophysiological in vivo and with immunohistochemistry by injection of Fluorogold. Results In the present work we found that injury of the tibial nerve innervating both muscle and skin but not of the sural nerve produced a lasting mechanical allodynia in adult rats;High frequency stimulation（HFS） or injury of the tibial nerve induced L-LTP of C-fiber evoked field potentials in spinal dorsal horn,lasting for more than 5 h,while HFS or injury of the sural nerve only induced early-phase LTP（E-LTP）,lasting less than 3 h.Furthermore,HFS of the tibial nerve induced L-LTP of C-fiber responses evoked by stimulation of the sural nerve and the heterosynaptic L-LTP was completely prevented by spinal application of TrkB-Fc（a BDNF scavenger）.Spinal application of BDNF at a dose as low as 10 pg/ml enabled HFS of the sural nerve to produce homosynaptic L-LTP.Importantly,our immunohistochemical results revealed that the number of BDNF-expressing neuron

关键词： sural nerve brain-derived neurotrophic factor neuropathic pain long-term potentiation spinal dorsal horn

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