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| 1 | 脊髓损伤的病理改变及修复策略显示文摘脊髓损伤造成神经组织坏死,传导通路中断,损伤平面以下运动和感觉功能丧失,导致瘫痪甚至死亡.脊髓损伤的病理变化极其复杂,早期主要为分子基因水平的改变,亚急性期主要为细胞组织水平的变化.这些变化引发继发性损伤,致使组织坏死、神经元死亡、轴突断裂并形成由瘢痕组织包裹的囊性空洞,抑制轴突再生.目前临床上仅能通过手术减压或者使用药物对症干预,无法从根本上改善受损神经的功能.脊髓损伤后功能难以恢复有多方面的原因:炎症反应贯穿脊髓损伤全过程,炎症介质导致损伤区域的神经元及胶质细胞变性坏死,轴突因瓦勒变性而萎缩;神经元再生能力弱,轴突再生乏力,并且瘢痕组织导致轴突无法穿越损伤区域与远端的轴突形成联系.本文就脊髓损伤后的病理改变进行综述并探讨修复策略. | 李建平 何留民 吴武田 | 2022 | 中国科学:生命科学2022，52，10： | 8 |
| 2 | Stem cell-based therapy for human diseases显示文摘Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated.Stem cell-based therapy,including human pluripotent stem cells(hPsCs)and multipotent mesenchymal stem cells(MSCs),has recently emerged as a key player in regenerative medicine.hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body,including three germ layers.MsCs are multipotent progenitor cells possessing self-renewal ability(limited in vitro)and differentiation potential into mesenchymal lineages,according to the International Society for Cell and Gene Therapy(ISCT).This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow(BM),adipose tissue(AT),or the umbilical cord(UC)for the treatment of human diseases,including neurological disorders,pulmonary dysfunctions,metabolic/endocrine-related diseases,reproductive disorders,skin burns,and cardiovascular conditions.Moreover,we discuss our own clinical trial experiences on targeted therapies using MsCs in a clinical setting,and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications,with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications.The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment,AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration,and UC-MsCs are potentially good candidates for pulmonary disease and acute respiratory distress svndrometreatment. | Duc M.Hoang Phuong T.Pham Trung Q.Bach Anh T.L.Ngo Quyen T.Nguyen Trang T.K.Phan Giang H.Nguyen Phuong T.T.Le Van T.Hoang Nicholas R.Forsyth Michael Heke Liem Thanh Nguyen | 2022 | Signal Transduction and Targeted Therapy2022，7，9： | 7 |
| 3 | Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury显示文摘Human umbilical cord mesenchymal stem cells(hUC-MSCs)are a promising candidate for spinal cord injury(SCI)repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources.However,modest clinical efficacy hampered the progression of these cells to clinical translation.This discrepancy may be due to many variables,such as cell source,timing of implantation,route of administration,and relevant efficacious cell dose,which are critical factors that affect the efficacy of treatment of patients with SCI.Previously,we have evaluated the safety and efficacy of 4×10^(6) hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models.To search for a more accurate dose range for clinical translation,we compared the effects of three different doses of hUC-MSCs-low(0.25×10^(6) cells/kg),medium(1×10^(6) cells/kg)and high(4×10^(6) cells/kg)-on subacute SCI repair through an elaborate combination of behavioral analyses,anatomical analyses,magnetic resonance imaging-diffusion tensor imaging(MRI-DTI),biotinylated dextran amine(BDA)tracing,electrophysiology,and quantification of mRNA levels of ion channels and neurotransmitter receptors.Our study demonstrated that the medium dose,but not the low dose,is as efficient as the high dose in producing the desired therapeutic outcomes.Furthermore,partial restoration of theγ-aminobutyric acid type A(GABAA)receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord.Overall,this study revealed that intrathecal implantation of 1×10^(6) hUC-MSCs/kg is an alternative approach for treating subacute SCI. | Ting-Ting Cao Huan Chen Mao Pang Si-Si Xu Hui-Quan Wen Bin Liu Li-Min Rong Mang-Mang Li | 2022 | Neural Regeneration Research2022，17，8： | 5 |
| 4 | 尿液细胞来源iPSCs-NSCs联合3D打印支架移植修复大鼠急性脊髓损伤的研究显示文摘目的探讨尿液细胞(UC)来源重编程诱导性多能干细胞(iPSCs)分化的神经干细胞(NSCs)联合3D打印支架移植修复大鼠急性脊髓损伤(ASCI)的作用。方法将UC诱导分化为iPSCs,通过ALP活性检测、HE染色观察畸胎瘤形成及免疫荧光检测全能性蛋白OCT4、NANOG、TRA-1-81、TRA-1-60的表达验证iPSCs全能性。将iPSCs向NSCs分化,免疫荧光染色检测巢蛋白(Nestin)、神经胶质原纤维酸性蛋白(GFAP)和β-微管蛋白(β-tubulinⅢ)的表达。制备3D打印支架。选择成年雄性SD大鼠42只,按随机数字表法分为模型组、支架模型组、iPSCs-NSCs组,每组14只。采用改良Allens法建立大鼠ASCI模型,1周后模型组于损伤处滴入DMEM培养液0.2 ml,支架模型组于损伤处植入载DMEM培养液的2~3 mm支架,iPSCs-NSCs组于损伤处植入载iPSCs-NSCs的2~3 mm支架。1、2、4、6、8周后采用开放领域运动测试(BBB)评分评价3组大鼠关节协调功能。8周后采用Tarlov和Rivlin评分评价3组大鼠后肢运动功能,生物信号采集处理系统观察大鼠运动、感觉诱发电位潜伏期和振幅;取伤段脊髓组织做病理检查,观察脊髓组织病理改变。结果成功提取UC并诱导分化为iPSCs,ALP染色呈阳性,HE染色显示畸胎瘤形成;免疫荧光染色显示全能性蛋白OCT4、NANOG、TRA-1-81、TRA-1-60表达。成功诱导iPSCs分化为NSCs,GFAP和β-tubulinⅢ表达良好表明细胞分化能力良好。成功打印3D支架,电镜显示内部呈三维立体疏松多孔结构。干预2、4、6、8周后,iPSCs-NSCs组大鼠BBB评分均高于模型组和支架模型组(均P<0.05);干预8周后,iPSCs-NSCs组大鼠Tarlov和Rivlin评分均高于模型组和支架模型组,运动和感觉诱发电位潜伏期均短于模型组和支架模型组,运动和感觉诱发电位振幅均大于模型组和支架模型组(均P<0.05)。HE染色显示模型组大鼠脊髓组织受损,组织水肿明显,细胞稀疏;支架模型组大鼠脊髓组织受损程度轻于模型组,组织水肿,细胞稀疏;iPSCs-NSCs组大鼠脊髓组织生长良好,细胞致密,空泡减小,组织水肿消失。结论UC来源iPSCs-NSCs联合3D打印支架移植可促进ASCI大鼠运动和感觉功能的恢复及受损节段脊神经纤维生长。 | 李长明 邵荣学 邓小梅 赵士杰 王拓 全仁夫 | 2021 | 浙江医学2021，43，3： | 3 |
| 5 | Expression and regulatory network of long noncoding RNA in rats after spinal cord hemisection injury显示文摘Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of right side hemisection of the spinal cord at T10,we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed.We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2,the two expression trends with the most significant difference.Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury.There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25.The co-expression network showed that the co-expressed genes were mainly enriched in cell division,inflammatory response,FcγR-mediated cell phagocytosis signaling pathway,cell cycle and apoptosis.The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury.There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2.The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction.The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways.These findings provide a new direction for the clinical treatment of spinal cord injury. | Wei Liu Jin-Cheng Tao Sheng-Ze Zhu Chao-Lun Dai Ya-Xian Wang Bin Yu Chun Yao Yu-Yu Sun | 2022 | Neural Regeneration Research2022，17，10： | 1 |
| 6 | 3D支架载尿液细胞来源IPSCs-NSCs移植对急性脊髓损伤大鼠的修复作用观察显示文摘目的将尿液细胞来源重编程诱导性多能干细胞(IPSCs)分化为神经干细胞(NSCs),与3D打印脊髓支架(简称3D支架)共培养后观察其对急性脊髓损伤(SCI)大鼠的修复作用。方法将尿液细胞来源IPSCs分化为NSCs,免疫荧光检测结果显示IPSCs-NSCs中的胶质纤维酸性蛋白(GFAP)和微管蛋白(β-tubulinⅢ)阳性表达,证实细胞分化能力良好。提取新生SD大鼠海马组织,制备Hd-NSCs并进行鉴定。制备3D支架,电镜显示内部呈三维立体疏松多孔结构。选择成年雄性SD大鼠56只,随机分为4组各14只,均建立SCI模型。建模1周后,IPSCs-NSCs组植入载IPSCs-NSCs的3D支架,Hd-NSCs组植入载Hd-NSCs的3D支架,模型组植入DMEM培养液0.2 mL,支架模型组植入载DMEM培养液的3D支架。比较各组术后2~8周开放领域运动测试(BBB)评分,术后8周Tarlov、Rivlin评分及运动、感觉诱发电位;术后8周处死,HE染色观察受损节段脊髓组织病理改变。结果IPSCs-NSCs组、Hd-NSCs组术后2~8周BBB评分及术后8周Tarlov评分、Rivlin评分、运动和感觉诱发电位振幅均高于模型组、支架模型组,术后8周运动和感觉诱发电位潜伏期均短于模型组、支架模型组(P均<0.05);IPSCs-NSCs组、Hd-NSCs组上述指标比较差异均无统计学意义(P均>0.05)。结论3D支架载尿液细胞来源重编程IPSCs-NSCs移植可改善急性SCI大鼠的运动及感觉功能、促进损伤处的脊神经纤维生长,其效果与海马来源的NSCs相当。 | 李长明 邵荣学 邓小梅 赵士杰 王拓 全仁夫 | 2020 | 山东医药2020，60，35： | 1 |
| 7 | 3D打印支架联合iPSCs-NSCs移植对大鼠急性脊髓损伤的修复作用研究显示文摘目的研究3D打印支架联合诱导性多潜能干细胞分化的神经干细胞(iPSCs-NSCs)移植对大鼠急性脊髓损伤的修复作用。方法制备3D打印支架,将人尿液细胞来源的iPSCs分化为NSCs。选择成年雌性SD大鼠56只,采用随机数字表法分为空白组(A组)、模型组(B组)、支架对照组(C组)、支架联合iPSCs-NSCs组(D组)4组,每组14只。除A组外,其余3组采用可控性皮质脊髓撞击仪复制急性脊髓损伤大鼠模型,1周后给予不同干预措施。术后8周,通过Basso-Beattie-Bresnahan(BBB)评分、Tarlov评分和Rivlin评分评价各组大鼠后肢的运动功能,采用诱发电位仪检测各组大鼠的运动诱发电位(MEP)、感觉诱发电位(SEP);取受损节段脊髓组织做病理切片,HE染色,镜下观察脊髓组织病理改变。结果与A组比较,B组大鼠术后不同时间BBB评分及术后8周Tarlov、Rivlin评分均明显降低,MEP、SEP潜伏期明显延长,振幅明显缩小,差异均有统计学意义(P<0.05);与B组比较,D组大鼠术后不同时间BBB评分及术后8周Tarlov、Rivlin评分均明显升高,MEP、SEP潜伏期明显缩短,振幅明显增大,差异均有统计学意义(P<0.05),C组与B组各项指标比较差异均无统计学意义(P>0.05);D组各项指标改善程度均明显优于C组,2组比较差异有统计学意义(P<0.05)。病理观察结果显示,D组脊神经生长良好,各组织生长间隙缩小,空泡减少,组织水肿消失。结论相对于单纯植入3D打印支架,3D打印支架联合iPSCs-NSCs移植能明显减轻急性脊髓损伤模型大鼠的脊髓组织空洞,促进脊髓神经纤维再生及运动、感觉功能的恢复。 | 李长明 邓小梅 全仁夫 | 2022 | 甘肃中医药大学学报2022，39，2： | 0 |
| 8 | 生物支架联合干细胞移植治疗脊髓损伤的研究进展显示文摘脊髓损伤是一种由外伤等原因引起的神经损伤性疾病,可导致患者损伤部位以下感觉和运动功能部分或全部丧失。目前脊髓损伤的治疗方法包括手术治疗、药物治疗、高压氧疗、脉冲电疗等,虽然这些方法能延缓脊髓损伤的进展,但对神经功能的改善效果并不理想。近年来有学者提出,干细胞移植能在一定程度上促进神经功能恢复,对于脊髓损伤患者的康复具有重要意义,但如何将干细胞高效地应用于脊髓损伤的治疗,仍是一项巨大的挑战。研究表明,将干细胞种植于生物支架后再移植于脊髓损伤部位,可显著提高干细胞存活率,促进损伤脊髓的恢复。但由不同生物材料制作而成的支架的移植效果存在差异,选择合适的生物支架对于促进脊髓损伤后的功能恢复具有重要意义。本研究通过总结国内外相关文献,分析干细胞移植治疗脊髓损伤的优势与不足,探讨生物支架联合干细胞移植治疗脊髓损伤的应用前景。 | 李涛 谭龙旺 | 2022 | 广西医学2022，44，23： | 0 |
| 9 | 人脐带间充质干细胞在脊髓损伤修复中的研究进展显示文摘脊髓损伤发病率和致残率高,至今尚无完全修复损伤脊髓的治疗方法。随着干细胞移植技术的发展,有望从根本上修复损伤的脊髓。而在所有干细胞中,人脐带间充质干细胞可能是最佳的移植选择。动物研究已证实人脐带间充质干细胞具有巨大的脊髓损伤修复潜力,但临床转化并不顺利。本文将着重讨论人脐带间充质干细胞对脊髓损伤的神经修复机制,以及临床最佳移植途径、剂量、时机和临床安全性、有效性。 | 李永超 冯晓飞 苏启航 谭军 李立钧 | 2023 | 同济大学学报(医学版)2023，44，5： | 0 |
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