尿源性干细胞及细胞外囊泡在组织损伤修复中的作用

doi:10.12307/2021.149

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (31): 5046-5052.doi: 10.12307/2021.149

• 干细胞综述 stem cell review • 上一篇下一篇

尿源性干细胞及细胞外囊泡在组织损伤修复中的作用

崔田宁1，刘涛1，肖向阳1，王帅2，张霓霓2，黄桂林2

1遵义医科大学，贵州省遵义市 563000；2遵义医科大学附属口腔医院颌面外科，贵州省遵义市 563000

收稿日期:2020-11-24 修回日期:2020-11-30 接受日期:2021-01-09 出版日期:2021-11-08 发布日期:2021-04-25
通讯作者: 黄桂林，博士，教授，硕士生导师，遵义医科大学附属口腔医院颌面外科，贵州省遵义市 563000
作者简介:崔田宁，女，1995年生，河南省新乡市人，汉族，遵义医科大学在读硕士，主要从事放射性组织(涎腺)损伤修复研究及口腔颌面外科疾病的诊治
基金资助:
国家自然科学基金项目(81760201，81960204)，项目负责人：黄桂林；国家自然科学基金项目(81860198)，项目负责人：张霓霓

Effect of urinary-derived stem cells and extracellular vesicles in tissue damage repair

Cui Tianning1, Liu Tao1, Xiao Xiangyang1, Wang Shuai2, Zhang Nini2, Huang Guilin2

1Zunyi Medical University, Zunyi 563000, Guizhou Province, China; 2Department of Dentofacial Surgery, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China

Received:2020-11-24 Revised:2020-11-30 Accepted:2021-01-09 Online:2021-11-08 Published:2021-04-25
Contact: Huang Guilin, MD, Professor, Master’s supervisor, Department of Dentofacial Surgery, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
About author:Cui Tianning, Master candidate, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
Supported by:
the National Natural Science Foundation of China, No. 81760201, 81960204 (to HGL); the National Natural Science Foundation of China, No. 81860198 (to ZNN)

摘要/Abstract

摘要：

文题释义：

尿源性干细胞：是从健康成人尿液中分离、提取培养得到的具有强大增殖能力、多向分化能力的一种细胞群体，不仅稳定地高表达间充质干细胞特异性表面标志物，还能表达胚胎干细胞特异性标志物，在细胞疗法和组织再生中具有广泛的可行性。
类器官：是干细胞衍生的一种三维微器官，与来源组织和器官高度相似；将分离的成人干细胞或所需器官培养的单细胞悬浮液，嵌入到细胞外基质水凝胶中来建立类器官，目前已制造出肝脏、胰脏、胃、心脏、肾脏甚至乳腺等在内的各种类器官。
背景：间充质干细胞及其细胞外囊泡在促进组织损伤修复与再生的应用研究中取得了很大进展，为将来无细胞治疗策略提供了临床应用前景。
目的：综述尿源性干细胞及其细胞外囊泡在泌尿系统、骨骼系统、神经系统中的修复作用，以及存在的问题及其应用前景。
方法：检索PubMed、万方数据库，以“尿源性干细胞，细胞外囊泡，组织损伤修复(膀胱、骨、神经等)”和“urine-derived stem cells，extracellular vesicles，tissue damage repair(bladder；bone；nerve tissue)”为中、英文检索词，检索的时间范围为1989至2020年。通过阅读文题和摘要进行初步筛选；排除中英文文献重复性研究以及内容不相关的文献，最后纳入62篇文献进行综述。
结果与结论：尿源性干细胞是从尿液中提取的具有多向分化潜能的细胞群，其生物学特性与间充质干细胞及胚胎干细胞类似。尿源性干细胞衍生细胞外囊泡是一种新的无细胞治疗策略，目前广泛应用于泌尿系统、骨骼系统、神经系统的组织修复。然而现阶段仍处于小型动物的实验研究，还需要进行大量的临床研究以证实其用于组织工程的安全性和可行性，因此尿源性干细胞及其细胞外囊泡将成为再生医学领域中的研究热点。
https://orcid.org/0000-0002-9328-7121(崔田宁)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 干细胞, 尿源性干细胞, 细胞外囊泡, 组织损伤, 修复, 泌尿组织, 肾脏, 骨骼, 神经组织, 综述

Abstract: BACKGROUND: Mesenchymal stem cells and their extracellular vesicles have made great progress in promoting the repair and regeneration of tissue injury, which provides a promising clinical application for future cell-free therapeutic strategies.
OBJECTIVE: To review the repair of urinary-derived stem cells and their extracellular vesicles in the urinary system, the skeletal system, the nervous system, as well as the problems and prospects.
METHODS: PubMed and Wanfang databases were searched using “urine-derived stem cells, extracellular vesicles, tissue damage repair (bladder; bone; nerve tissue)” as Chinese and English search terms. The retrieve time range was from 1989 to 2020. By reading titles and abstracts for initial screening, repetitive studies and articles with irrelevant contents in English and Chinese literature were excluded. Finally, 62 articles were reviewed.
RESULTS AND CONCLUSION: Urine-derived stem cells are a group of cells with multi-directional differentiation potential extracted from urine, and their biological characteristics were similar to mesenchymal stem cells and embryonic stem cells. Extracellular vesicles derived from urine-derived stem cells are a kind of new cell free treatment strategy, which is currently widely used in tissue repair in the urinary system, skeletal system and nervous system. At present, it is still in the small animal experimental study; however, a large number of trials are required to confirm the safety and feasibility of tissue engineering. Thus, the urine-derived stem cells and extracellular vesicles will become a hot spot in the field of regenerative medicine.

Key words: stem cells, urine-derived stem cells, extracellular vesicles, tissue damage, repair, urinary tissue, kidney, bone, nerve tissue, review

中图分类号:

崔田宁, 刘涛, 肖向阳, 王帅, 张霓霓, 黄桂林. 尿源性干细胞及细胞外囊泡在组织损伤修复中的作用[J]. 中国组织工程研究, 2021, 25(31): 5046-5052.

Cui Tianning, Liu Tao, Xiao Xiangyang, Wang Shuai, Zhang Nini, Huang Guilin. Effect of urinary-derived stem cells and extracellular vesicles in tissue damage repair[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(31): 5046-5052.

图/表（结果） 1

参考文献

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引言

材料方法

讨论

近10年来，大量研究表明尿源性干细胞及其细胞外囊泡已被用作新型非创伤性来源细胞，在生物组织工程和再生修复学中具有广泛的可行性，尤其是在泌尿组织工程中，并且还可以作为通过重新编程进行疾病建模的原始细胞。但是，由于尚未对尿源性干细胞及其细胞外囊泡的生物学特性进行全面研究，因此在将其应用于临床治疗之前，还需要进一步进行基础研究和实验动物研究，也有一些问题尚待解决。首要问题是关于细胞行为，几乎没有证据表明尿源性干细胞可以移植到组织(特别是人体)中并在体内分化。在大多数动物体内实验中，只有微量被标记的尿源性干细胞能被检测，在使用生物相容性和可生物降解支架后可能会促进细胞植入，但是即使尿源性干细胞及其细胞外囊泡保留在该组织中，其真正的分化能力仍有待证明；次要问题是关于注射时间、给药途径和剂量也是关键因素等，这些因素可能对细胞治疗的有效性至关重要[61]。
目前大量实验研究表明，尿源性干细胞及其细胞外囊泡参与了许多组织生物学过程，不但能降低组织损伤和改善许多器官的组织修复和功能，而且由于其具有旁分泌作用，对泌尿系统、骨组织、神经组织、肌组织损伤等均能表现出较好的治疗效果，为组织工程和再生医学策略开辟了多种新途径[62]。近来发现间充质干细胞衍生的胞外囊泡可通过减少炎症反应，促进细胞增殖、抑制细胞凋亡和促进血管生成等来增强组织再生和修复，特别是细胞外囊泡免疫原性低又便于保存和运输，还具有通过预处理增加治疗潜力等优势。此外，通过干细胞永生化培养技术，可以实现大规模细胞外囊泡制备的可能。因此，基于以上这些发现，尿源性干细胞来源的细胞外囊泡也有望在再生医学领域中成为一种新的无细胞治疗策略。
结论：尽管尿源性干细胞及其细胞外囊泡在组织工程学中已取得了巨大的进展，但大多数研究人员主要通过兔和鼠动物研究而不是大型动物来进行实验，另外仍需要进行大量的临床研究以证实其用于组织工程的安全性和可行性。可预见的是，尿源性干细胞及其细胞外囊泡在再生医学领域的影响持续增加，在未来几年都将成为生物医学中的研究热点。
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

尿源性干细胞及细胞外囊泡在组织损伤修复中的作用

Effect of urinary-derived stem cells and extracellular vesicles in tissue damage repair

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