Olfactory ecto-mesenchymal stem cells possess immunoregulatory function and suppress autoimmune arthritis

Recent studies have identified olfactory ecto-mesenchymal stem cells （OE-MSCs） as a new type of resident stem cell in the olfactory lamina propria. However, it remains unclear whether OE-MSCs possess any immunoregulatory functions. In this study, we found that mouse OE-MSCs expressed higher transforming growth factor-beta and interleukin-10 levels than bone marrow-derived MSCs. In culture, OE-MSCs exerted their immunosuppressive capacity via directly suppressing effector T-cell proliferation and increasing regulatory T （Treg） cell expansion. In mice with collagen-induced arthritis, adoptive transfer of OE-MSCs markedly suppressed arthritis onset and disease severity, which was accompanied by increased Treg cells and reduced Th1/Th17 cell responses in vivo. Taken together, our findings identified a novel function of OE-MSCs in regulating T-cell responses, indicating that OE-MSCs may represent a new cell therapy for the treatment of rheumatoid arthritis and other autoimmune diseases.

Combined Transplantation of Neural Stem Cells and Olfactory Ensheathing Cells Improves the Motor Function of Rats with Intracerebral Hemorrhage

Objective To investigate the effects of combined transplantation of neural stem cells （NSC） and olfactory ensheathing cells （OEC） on the motor function of rats with intracerebral hemorrhage. Methods In three days after a rat model of caudate nucleus hemorrhage was established, NSCs and OEC, NSC, OEC （from embryos of Wistar rats） or normal saline were injected into bematomas of rats in combined transplantation group, NSC group, OEC group, and control group, respectively. Damage of neural function was scored before and in 3, 7, 14, 30 days after operation. Tissue after transplantation was observed by immunocytochemistry staining. Results The scores for the NSC, OEC and co-transplantation groups were significantly lower in 14 and 30 days after operation than in 3 days after operation （P〈0.05）. The scores for the NSC and OEC groups were significantly lower than those for the control group only in 30 days after operation （P〈0.05）, while the difference for the NSC-OEC group was significant in 14 days after operation （P〈0.05）. Immunocytochemistry staining revealed that the transplanted OEC and NSC could survive, migrate and differentiate into neurons, astrocytes, and oligodendrocytes. The number of neural precursor cells was greater in the NSC and combined transplantation groups than in the control group. The number of neurons differentiated from NSC was significantly greater in the co-transplantation group than in the NSC group. Conclusion Co-transplantation of NSC and OEC can promote the repair of injured tissue and improve the motor fimction of rats with intracerebral hemorrhage.

Transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury:A Web of Science-based literature analysis

OBJECTIVE： To identify global research trends in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. DATA RETRIEVAL： We performed a bibliometric analysis of studies on transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury published from 2002 to 2011 and retrieved from the Web of Science, using the key words spinal cord injury along with either neural stem cell, Schwann cell or olfactory ensheathing cell. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on neural stem cells, Schwann cells or olfactory ensheathing cells for spinal cord injury indexed in the Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial materials and news items; and （c） published between 2002 and 2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） corrected papers. MAIN OUTCOME MEASURES： （1）Annual publication output, distribution by journal, distribution by institution and top-cited articles on neural stem cells; （2） annual publication output, distribution by journal, distribution by institution and top-cited articles on Schwann cells; （3） annual publication output, distribution by journal, distribution by institution and top-cited articles on olfactory ensheathing cells. RESULTS： This analysis, based on articles indexed in the Web of Science, identified several research trends among studies published over the past 10 years in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. The number of publications increased over the 10-year period examined. Most papers appeared in journals with a focus on neurology, such as Journal of Neurotrauma, Experimental Neurology and Gila. Research institutes publishing on the use of neural stem cells to repair spinal cord injury were mostly in the USA and Canada. Those publishing on the use of Schwann cells were mostly in the USA and Canada as well. Those publishing on the use of olfactory ensheathing cells were mostly in the UK, the USA and Canada. CONCLUSION： On the basis of the large number of studies around the world, cell transplantation has proven to be the most promising therapeutic approach for spinal cord injury.

Effects of olfactory ensheathing cells on the proliferation and differentiation of neural stem cells

BACKGROUND： Olfactory ensheathing cells can promote oriented differentiation and proliferation of neural stem cells by cell-secreted neural factors. OBJECTIVE： To observe the effect of olfactory ensheathing cells on the differentiation and proliferation of neural stem cells. DESIGN, TIME AND SETTING： Cytology was performed at the Department of Neurology, Tongji Medical College, Huazhong University of Science and Technology, China, from September 2007 to October 2008. MATERIALS： Mouse anti-nestin polyclonal antibody （Chemicon, USA）, mouse anti-glial fibrillary acidic protein （GFAP） IgG1, mouse anti-2＇, 3＇-cyclic nucleotide 3＇-phosphodiesterase （CNPase） IgG1, mouse anti-Tubulin Class-Ill IgG1 （Neo Markers, USA）, Avidin-labeled Cy3 （KPL, USA）, and goat anti-mouse IgGl： fluorescein isothiocyanate （FITC） （Serotec, UK） were used in this study. METHODS：Tissues were isolated from the embryonic olfactory bulb and subependymal region of Wistar rats. Serum-free DMEM/F12 culture media was used for co-culture experiments. Neural stem cells were incubated in serum-free or 5% fetal bovine serum-containing DMEM/F12 as controls. MAIN OUTCOME MEASURES： After 7 days of co-culture, neural stem cells and olfactory ensheathing cells underwent immunofluorescent staining for nestin, tubulin, glial fibrillary acidic protein, and CNPase. RESULTS： Olfactory ensheathing cells promoted proliferation and differentiation of neural stem cells into neuron-like cells, astrocytes and oligodendrocytes. The proportion of neuron-like cells was 78.2%, but the proportion of neurons in 5% fetal bovine serum DMEM/F12 was 48.3%. In the serum-free DMEM/F12, neural stem cells contracted, unevenly adhered to the glassware wall, or underwent apoptosis at 7 days. CONCLUSION： Olfactory ensheathing cells promote differentiation of neural stem cells mainly into neuron-like cells, and accelerate proliferation of neural stem cells. The outcome is better compared with serum-free medium or medium containing 5% fetal bovine serum.

Intranasal Administration of Conditioned Medium from Cultured Mesenchymal Stem Cells Improves Cognitive Impairment in Olfactory Bulbectomized Mice

Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-β (Aβ) and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show some of AD features, so they have been used to research as AD model. Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, including neuronal cells. In this study, we intranasally administrated the conditioned medium derived from cultured umbilical cord (UC) MSCs. The intranasal administration of the MSCs medium restored the cognitive impairment observed in OBX mice. In addition, the decreased number of choline acetyltransferase-positive cells in the medial septum was restored by the conditioned medium administration. In conclusion, MSCs-derived conditioned medium may have protective effects of cholinergic neurons in the medial septum, thereby rescuing the cognitive impairment of OBX.

Expression and subcellular localization of cysteine- and glycine-rich protein-2 in rat undifferentiated olfactory stem cells

BACKGROUND： As a member of the LIM protein family Ⅱ, cysteine- and glycine-rich protein-2 （CRP2） has been demonstrated to play a role in the regulation of growth and differentiation of eukaryotic cells. Our previous study has demonstrated that CRP2 can be detected in the embryonic rat inner ear but not in the adult rat inner ear. However, at present, the expression of LIM protein family H members in stem or precursor cells has not been described. OBJECTIVE： To determine the expression and sub-cellular localization of CRP2 in olfactory stem cells. DESIGN, TIME AND SETTING： An experiment with repeated measures was performed in the Laboratory of Otorhinolaryngology, Head and Neck Surgery, Xijing Hospital, the Fourth Military Medical University from February 2008 to April 2008. MATERIALS： Olfactory stem cells, and rabbit-anti-CRP2 polyclonal antibody were prepared and kept in our laboratory. METHODS： Reverse transcription polymerase chain reaction and Western blot analysis were used to detect expression of CRP2 in olfactory stem cells. Immunocytochemistry was also used to localize CRP2 in olfactory stem cells. MAIN OUTCOME MEASURES： The expression and sub-cellular localization of CRP2 in rat olfactory stem cells. RESULTS： CRP2 expression was found in olfactory stem cells, and CRP2 was distributed in both the nucleus and the cytoplasm. CONCLUSION： Confirmation of the expression and distribution of CRP2 in olfactory stem cells.

Adult neural stem cells in the mammalian central nervous system

Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.

Adult neural stem cell dysfunction in the subventricular zone of the lateral ventricle leads to diabetic olfactory defects

Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.

Adult stem cells in neural repair: Current options, limitations and perspectives

Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseasesthat defy doctors and researchers around the world. Stem cells can be divided into three main groups:(1) embryonic stem cells;(2) fetal stem cells; and(3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, pluripotent or multipotent. Adult stem cells, also known as somatic cells, are found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain. They can differentiate into unipotent cells of the residing tissue, generally for the purpose of repair. These cells represent an excellent choice in regenerative medicine, every patient can be a donor of adult stem cells to provide a more customized and efficient therapy against various diseases, in other words, they allow the opportunity of autologous transplantation. But in order to start clinical trials and achieve great results, we need to understand how these cells interact with the host tissue, how they can manipulate or be manipulated by the microenvironment where they will be transplanted and for how long they can maintain their multipotent state to provide a full regeneration.

Ocular stem cells:a narrative review of current clinical trials

·Stem cells are undifferentiated cells showcasing a remarkable capacity of self-replenishing and differentiating into mature cells.Their ability to proliferate connotes that a designated stem cell source is capable of generating an unrestricted number of mature cells.The ever-increasing comprehension of position,activity,and function of ocular stem cells has led to rapid progress and incessant improvement of possible procedures and therapies.A narrative review was conducted to summarize the current evidence on clinical trials and respective literature,regarding current evolution in the field of ocular regenerative medicine.We tried to ascertain the safety of experimental and clinical procedures,their effectiveness,and the ethical repercussion of their use.

ADAM10 facilitates rapid neural stem cell cycling and proper positioning within the subventricular zone niche via JAMC/RAP1Gap signaling

The mechanisms that regulate neural stem cell(NSC)lineage progression and maintain NSCs within diffe rent domains of the adult neural stem cell niche,the subventricular zone are not well defined.Quiescent NSCs are arranged at the apical ventricular wall,while mitotically activated NSCs are found in the basal,vascular region of the subventricular zone.Here,we found that ADAM 10(a disintegrin and metalloproteinase 10)is essential in NSC association with the ventricular wall,and via this adhesion to the apical domain,ADAM10 regulates the switch from quiescent and undiffe rentiated NSC to an actively prolife rative and differentiating cell state.Processing of JAMC(junctional adhesion molecule C)by ADAM 10 increases Rap1 GAP activity.This molecular machinery promotes NSC transit from the apical to the basal compartment and subsequent lineage progression.Understanding the molecular mechanisms responsible for regulating the proper positioning of NSCs within the subventricular zone niche and lineage progression of NSCs could provide new targets for drug development to enhance the regenerative prope rties of neural tissue.

MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

不同胚层来源成体干细胞修复周围神经损伤

背景:成体干细胞疗法是周围神经损伤修复与再生领域的研究热点之一。中胚层被视为成体干细胞的理想来源,间充质干细胞具有获得率高、来源广、增殖快等优异性能。而外胚层来源成体干细胞,尤其是神经嵴干细胞,具有神经源性,越来越受到研究人员的关注。目的:对来自外胚层和中胚层的多功能成体干细胞在周围神经损伤修复与再生中的作用及机制进行简要综述,探究不同来源成体干细胞的研究进展与应用前景,并结合临床研究,探讨成体干细胞疗法潜在的应用价值以及亟待解决的问题。方法:第一作者于2024年2月应用计算机在PubMed和SinoMed数据库检索2001年12月至2024年2月相关文献,以“ectodermal stem cells,mesenchymal stem cells,peripheral nerve injury,repair,regeneration”为英文检索词,以“外胚层干细胞、间充质干细胞、周围神经损伤、修复、再生”为中文检索词,最终纳入69篇文献进行分析论述。结果与结论:①外胚层来源成体干细胞具有优异的分化和再生潜能,尤其是毛囊神经嵴干细胞、嗅干细胞、牙外胚层干细胞等,具有神经源性,可在体外表达神经特异性标志物,但目前缺少临床试验研究。②中胚层来源成体干细胞种类多、易获得及纯化,其中骨髓间充质干细胞和脐带间充质干细胞在周围神经损伤修复的应用疗效及安全性方面有相关临床试验支持,能改善感觉及运动神经传导,且在随访中未出现并发症和明显不良反应。骨髓间充质干细胞的获取需行侵入性外科手术且要求患者与捐赠者骨髓配型吻合,应用受到一定限制;而脐带间充质干细胞虽无需侵入性获取,但分离较困难且表型不稳定。③内胚层来源成体干细胞常难以在体外生长,应用受限,目前应用于临床的可能性低。④综合来看,骨髓间充质干细胞仍为周围神经损伤干细胞治疗的首选细胞,适用于无外科手术禁忌且符合配型要求的情况,其次为脐带间充质干细胞,辅以分离方法的改进和表型稳定性的提高策略。⑤牙外胚层干细胞以及脂肪间充质干细胞具有较高应用潜能,有待进一步临床试验,其他外胚层、中胚层来源成体干细胞各以其优异特性在动物及细胞实验研究中具有显著优势。

嗅觉训练在造血干细胞移植患者中的应用研究

目的探讨嗅觉训练对行造血干细胞移植患者移植(HSCT)前后嗅觉水平、营养状况及自我感觉负担的影响。方法便利选取2021年6月-2022年3月在我院拟行HSCT的86例患者作为研究对象,按照随机数字表法分为观察组43例和对照组43例。2组患者均实施HSCT中心常规护理,观察组在常规护理基础上进行嗅觉训练。比较2组患者的嗅觉功能得分、血清白蛋白(ALB)、体重下降率、自我感觉负担量表(SPBS)得分。结果86例患者全部完成本研究。(1)干预6周后,观察组气味察觉阈(T)得分为(8.36±2.58)分,高于对照组(6.76±3.15)分,观察组气味辨别能力(D)得分为(57.41±13.27)分,高于对照组(51.26±13.41)分,观察组嗅觉水平总得分为(29.55±5.00)分,高于对照组(26.14±6.68)分,2组比较差异均有统计学意义(P<0.05)。但观察组气味识别(I)能力(40.98±24.32)分,低于对照组(41.37±24.73)分,2组比较差异无统计学意义(P>0.05)。(2)干预6周后,观察组血清白蛋白检测结果为(39.33±3.82)g/L,高于对照组(36.72±4.57)g/L,观察组体重下降率≥5%为15例,<5%为28例,对照组体重下降率≥5%为25例,<5%为18例,2组比较差异有统计学意义(P<0.05)。(3)干预后6周,观察组患者自我感觉负担得分为(27.90±7.72)分,低于对照组(30.94±6.98)分,2组比较差异有统计学意义(P<0.05)。结论对行HSCT患者进行嗅觉训练,可有效提高其整体嗅觉功能及ALB数值;降低患者体重下降率及自我感觉负担。

Neurogenesis in the adult olfactory bulb

Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricles. Cells of the subventricular zone divide and migrate via the rostral migratory stream to the olfactory bulb where they differentiate into granule and pefiglomerular cells. With the discovery of large-sca^e neurogenesis in the adult brain, there have been significant efforts to identify the mechanisms that control this process as well as the role of these cells in neuronal functioning. Although many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. In this review we highlight the main studies investigating factors that regulate neurogenesis in the subventricular zone, neuronal migration to the olfactory bulb, neuronal integration into the existing bulbar network and shortly discuss the functional meaning of this process.

Research progress on the treatment of spinal cord injury with cellular transplantation

Spinal cord injury（SCI） is a severe trauma to the central nervous system（CNS）. This article reviews recent advances in cellular transplantation to treat SCI. Transplanted cells can supply new neurons to replace injured ones, promote regeneration of axons and myelin sheath, modulate the inflammatory response, and thus promote recovery from traumatic injury of the CNS. Cellular transplantation is a promising potential method for the treatment of SCI.

Neural stem cells:mechanisms and modeling

In the adult brain,neural stem cells have been found in two major niches:the hippocampus and the olfactory bulb.Neurons derived from these stem cells contribute to learning,memory,and the autonomous repair of the brain under pathological conditions.Hence,the physi-ology of adult neural stem cells has become a signifi-cant component of research on synaptic plasticity and neuronal disorders.In addition,the recently developed induced pluripotent stem cell technique provides a powerful tool for researchers engaged in the patho-logical and pharmacological study of neuronal disor-ders.In this review,we briefly summarize the research progress in neural stem cells in the adult brain and in the neuropathological application of the induced pluripotent stem cell technique.

神经干细胞联合神经营养因子-3基因修饰的嗅鞘细胞移植对创伤性脑损伤大鼠神经功能的影响及机制

目的 探讨神经干细胞(NSCs)与神经营养因子-3(NT-3)基因修饰的嗅鞘细胞(OECs)联合移植对大鼠创伤性颅脑损伤(TBI)后神经功能的影响及机制。方法 将100只Sprague Dawley雄性大鼠按照随机数字表法分为假手术组、模型组、NSCs组、OECs组、联合治疗组,每组20只。模型组、NSCs组、OECs组、联合治疗组大鼠采用改良Feeney法构建TBI模型。造模1 d后,将不同的试剂注入各组大鼠损伤灶进行细胞移植,模型组大鼠注入10μL生理盐水,OECs组大鼠注入10μL NT-3基因修饰的OECs悬液,NSCs组大鼠注入10μL NSCs悬液,联合治疗组大鼠注入5μL NT-3基因修饰的OECs细胞悬液和5μL NSCs悬液,注射完成后继续常规饲养。分别于移植后1、7、14、28 d,各组随机取10只大鼠,采用改良神经功能缺损评分(mNSS)评估各组大鼠的神经功能缺损程度。移植后7 d,采用酶联免疫吸附试验法检测大鼠脑组织中白细胞介素(IL)-6、IL-1β及神经生长因子(NGF)水平。移植后28 d,采用苏木精-伊红染色法观察大鼠脑组织病理学改变,采用免疫组织化学染色法检测大鼠脑组织中NGF表达。结果 移植后1、7、14、28 d,模型组、NSCs组、OECs组、联合治疗组大鼠mNSS评分显著高于假手术组(P<0.05);移植后7、14 d,NSCs组、OECs组、联合治疗组大鼠mNSS评分显著低于模型组(P<0.05);移植后7、14 d,NSCs组、OECs组、联合治疗组大鼠mNSS评分比较差异无统计学意义(P>0.05);移植后28 d,NSCs组、OECs组、联合治疗组大鼠mNSS评分显著低于模型组,联合治疗组大鼠mNSS评分显著低于NSCs组和OECs组(P<0.05);移植后28 d,NSCs组与OECs组大鼠mNSS评分比较差异无统计学意义(P>0.05)。移植后28 d,假手术组大鼠脑组织结构完整,核仁明显,细胞排列有序;模型组大鼠损伤灶周围脑组织形态不规则,细胞肿胀,排列紊乱,可见坏死细胞及细胞核固缩,存在炎症细胞浸润;相较于模型组,NSCs组及OECs组大鼠脑组织细胞肿胀,排列紊乱,细胞核固缩、炎症浸润现象稍有改善;相较于模型组、NSCs组及OECs组,联合治疗组大鼠脑组织细胞排列相对规整,细胞肿胀减轻,核仁清晰。模型组大鼠脑组织中IL-6、IL-1β表达水平显著高于假手术组(P<0.05),联合治疗组大鼠IL-6、IL-1β表达水平显著低于模型组、NSCs组、OECs组(P<0.05),NSCs组、OECs组大鼠脑组织中IL-6、IL-1β水平显著低于模型组(P<0.05)。NSCs组、OECs组、联合治疗组大鼠脑组织中NGF阳性表达细胞数及NGF水平显著高于假手术组、模型组(P<0.05);假手术组与模型组大鼠脑组织中NGF阳性表达细胞数和NGF水平比较差异无统计学意义(P>0.05);联合治疗组大鼠脑组织中NGF阳性表达细胞数及NGF水平显著高于NSCs组、OECs组(P<0.05);NSCs组与OECs组大鼠脑组织中NGF阳性表达细胞数及NGF水平比较差异无统计学意义(P>0.05)。结论 NSCs和NT-3基因修饰的OECs联合移植治疗可显著减轻TBI大鼠神经功能缺损程度,提高NGF表达水平,减轻炎症反应,从而起到神经保护作用。

骨髓间充质干细胞与嗅鞘细胞联合移植治疗脊髓损伤的早期观察

[目的]探讨自体骨髓间充质细胞和异体嗅鞘细胞共培养及其联合移植修复脊髓损伤的可行性，为临床治疗提供一种新方法。[方法]无菌条件下采集自体骨髓间充质细胞和胎龄4～6个月的引产胎儿的嗅鞘细胞，分别培养至传代后再共培养，将共培养的混合细胞通过手术直视下移植至脊髓损伤部位。[结果]8例脊髓损伤患者接受自体骨髓间充质细胞和异体嗅鞘细胞联合移植，并获得1～6个月的随访，所有接受细胞移植的8例患者术后均无不良反应，其中1例术后1个月开始出现双下肢深浅感觉恢复，其余7例比细胞移植前无明显改善。[结论]自体骨髓间充质细胞和异体嗅鞘细胞共培养两者之间无相互抑制现象，近期观察二者联合移植修复脊髓损伤是安全的。

大鼠嗅粘膜原代培养细胞的分类及细胞社会学特性研究

目的 :探讨嗅粘膜的细胞社会学特性 ,为嗅粘膜混合细胞移植治疗中枢神经系统损伤提供可行性研究资料。方法 :自成年大鼠鼻中隔活体剪取部分嗅粘膜制成细胞悬液接种于玻璃培养皿 ,用含 10 %胎牛血清的F12培养基培养 ,动态观察细胞的贴壁、生长及分化过程 ,并用波形蛋白 (vimentin)、层粘连蛋白 (laminin)、巢蛋白 (nestin)、神经元特异性烯醇化酶 (neuronspecificenolase,NSE)、胶质纤维酸性蛋白 (glialfibrillaryacidicprotein ,GFAP)及神经生长因子受体 p75(nervegrowthfactorreceptorp75,NGFRp75)抗体作免疫细胞化学染色 ,对阳性细胞进行形态学鉴定。结果 :体外培养的嗅粘膜细胞中包含成纤维细胞、神经干细胞、嗅细胞和嗅鞘细胞等 ,不同类型细胞的形态及生长特性存在差异。结论 :嗅粘膜细胞之间具有协调的细胞社会学关系 ;成体嗅粘膜混合细胞群移植治疗中枢神经系统损伤的可行性具有细胞社会学基础。