切换至 "中华医学电子期刊资源库"
高级检索
中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2020, Vol. 10 ›› Issue (05) : 314 -318. doi: 10.3877/cma.j.issn.2095-1221.2020.05.011

所属专题： 文献；

综述

三维培养的间充质干细胞球体的生物学特性及应用的研究进展
唐敏英1, 雷艳2, 詹世淮3, 李荣春3, 路君1, 吴仲秋4,†()   
  1. 1. 350025　福州，联勤保障部队第900医院基础医学实验室；350025　福州，联勤保障部队第900医院福建省移植生物学重点实验室
    2. 350025　福州，联勤保障部队第900医院检验科
    3. 350025　福州，联勤保障部队第900医院基础医学实验室
    4. 350025　福州，联勤保障部队第900医院超声诊断科
  • 收稿日期:2020-06-01 出版日期:2020-10-01
  • 通信作者: 吴仲秋
  • 基金资助:
    联勤保障部队第900医院院内课题战时伤病救治研究专项(2018Z05)

Advances in biological characteristics and applications of mesenchymal stem cells spheroids under three-dimensional culture

Minying Tang1, Yan Lei2, Shihuai Zhan3, Rongchun Li3, Jun Lu1, Zhongqiu Wu4,†()   

  1. 1. Basic Medical Laboratory, the 900th Hospital of Joint Logistics Support Force, Fuzhou 350025, China; Key Laboratory of Transplant Biology, the 900th Hospital of Joint Logistics Support Force, Fuzhou 350025, China
    2. Clinical Laboratory, the 900th Hospital of Joint Logistics Support Force, Fuzhou 350025, China
    3. Basic Medical Laboratory, the 900th Hospital of Joint Logistics Support Force, Fuzhou 350025, China
    4. Department of Ultrasound Diagnosis, the 900th Hospital of Joint Logistics Support Force, Fuzhou 350025, China
  • Received:2020-06-01 Published:2020-10-01
  • Corresponding author: Zhongqiu Wu
  • About author:
    Corresponding author:Wu Zhongqiu, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

唐敏英, 雷艳, 詹世淮, 李荣春, 路君, 吴仲秋. 三维培养的间充质干细胞球体的生物学特性及应用的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2020, 10(05): 314-318.

Minying Tang, Yan Lei, Shihuai Zhan, Rongchun Li, Jun Lu, Zhongqiu Wu. Advances in biological characteristics and applications of mesenchymal stem cells spheroids under three-dimensional culture[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(05): 314-318.

二维（2D）贴壁培养是间充质干细胞体外扩增的标准技术，但其局限性也很明显，比如组织特异性的结构、生物学行为及细胞间的相互作用在2D环境中缺失。三维（3D）培养是一种模拟体内生长环境的细胞培养方式，通过让细胞聚集成3D球体或者将细胞在成分结构类似于实体组织的3D结构载体上黏附、伸展和生长，从时间和空间上共同调控细胞的增殖和分化，使特性和功能得以较大程度保留。与2D培养相比，3D培养增强了细胞与细胞之间以及细胞与胞外基质之间的相互作用，更准确地模拟细胞在体内的自然微环境。3D培养也解决了MSCs在体外增殖能力减低的问题，MSCs成脂、成骨和成软骨的能力增强。MSCs球体的制备（微球体黏附培养）被认为是提高MSCs细胞疗法的优化方式之一，MSCs球体的形成能增强抗炎作用、增强血管生成、增加组织再生和修复作用并提高MSCs移植后的存活率。本文就微球体黏附培养MSCs的生物学特性及其应用进展进行综合阐述。

关键词: 间充质干细胞, 三维培养, 血管生成, 组织修复, 骨组织再生

Traditionally, two-dimensional (2D) adherent culture conditions have been used as a standard technique for in vitro expansion of mesenchymal stem cells (MSCs) , but their limitations are also obvious, such as the absence of tissue-specific structures, biological behavior and cellular interactions in the two-dimensional environment. In contrast, 3D cell culture is regarded as a mode simulating the growth environment in vivo. By aggregating cells into 3D spheres or attaching, extending, and growing on three-dimensional structural vectors whose components are similar to solid tissue, cell proliferation and differentiation are regulated in both time- and space-dependent manners. Thus, the characteristics and functions of cells cultured in 3D can be better preserved. The 3D spheroid culture enhances cell-cell and cell-extracellular matrix (ECM) interactions and closely mimics the natural microenvironment of a tissue as compared with traditional 2D monolayer culture. In addition, 3D culture also solves the problem of decreased proliferation of MSCs in vitro, and the capabilities of adipogenesis, osteogenesis and chondrogenesis of MSC spheroids were significantly enhanced in 3D culture. In conclusion, the preparation of MSCs spheroids (microsphere adhesion culture) is considered as one of the optimal ways to improve MSCs-based cell therapy. The application of 3D MSCs spheroids can enhance anti-inflammatory effect, promote angiogenesis, increase tissue regeneration and repair, and improve the survival rate of MSCs after transplantation. In this review, we discuss the biological characteristics and applications of MSCs spheroids under three-dimensional culture.

Key words: Mesenchymal stem cells, Three-dimensional culture, Angiogenesis, Tissue repair, Bone tissue regeneration
1
Abbasi-Malati Z, Roushandeh AM, Kuwahara Y, et al. Mesenchymal stem cells on horizon: a new arsenal of therapeutic agents[J]. Stem cell Rev Rep, 2018, 14(4):484-499.
2
Cesarz Z, Tamama K. Spheroid culture of mesenchymal stem cells[J]. Stem Cells Int, 2016, 2016:9176357. doi:10.1155/2016/9176357.
3
Ravi M, Paramesh V, Kaviya SR, et al. 3D cell culture systems: Advantages and applications[J]. J Cell Physiol, 2015, 230(1):16-26.
4
Knight E, Przyborski S. Advances in 3D cell culture technologies enabling tissue-like structures to be created in vitro[J]. J Anat, 2015, 227(6):746-756.
5
詹世淮，雷艳，黄梁浒, 等. 三维细胞培养技术应用于肿瘤细胞的研究进展[J/CD]. 中华细胞与干细胞杂志(电子版), 2016, 6(4):248-251.
6
Williams EK, García JR, Mannino RG, et al. Enabling mesenchymal stromal cell immunomodulatory analysis using scalable platforms[J]. Integr Biol (Camb), 2019, 11(4):154-162.
7
Choi J, Lee EK, Choo J, et al. Micro 3D cell culture systems for cellular behavior studies:culture matrices, devices, substrates, and in-situ sensing methods[J]. Biotechnol J, 2015, 10(11):1682-1688.
8
Jakubikova J, Cholujova D, Hideshima T, et al. A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche: biologic and clinical applications[J]. Oncotarget, 2016, 7(47): 77326-77341.
9
Bellotti C, Duchi S, Bevilacqua A, et al. Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entrylevel equipment[J]. Cytotechnology, 2016, 68(6):2479-2490.
10
Zhou Y, Chen H, Li H, et al. 3D culture increases pluripotent gene expression in mesenchymal stem cells through relaxation of cytoskeleton tension[J]. J Cell Mol Med, 2017, 21(6):1073-1084.
11
Mo MH, Zhou Y, Li S, et al. Three-dimensional culture reduces cell size by increasing vesicle excretion[J]. Stem cells, 2018, 36(2):286-292.
12
Bae YJ, Kwon YR, Kim HJ, et al. Enhanced differentiation of mesenchymal stromal cells by three-dimensional culture and azacitidine[J]. 2017, 52(1):18-24.
13
Shekaran A, Sim E, Tan KY, et al. Enhanced in vitro osteogenic differentiation of human fetal MSCs attached to 3D microcarriers versus harvested from 2D monolayers[J]. BMC Biotechnol, 2015, 15:102.
14
Chatterjea A, LaPointe VL, Barradas A, et al. Cell aggregation enhances bone formation by human mesenchymal stromal cells[J]. Eur Cell Mater, 2017, 33:121-129.
15
Tietze S, Kräter M, Jacobi A, et al. Spheroid culture of mesenchymal stromal cells results in morphorheological properties appropriate for improved microcirculation[J]. Adv Sci, 2019, 6(8):1802104.
16
Saleh F, Carstairs A, Etheridge SL, et al. Real-time analysis of endogenous wnt signalling in 3D mesenchymal stromal cells[J]. Stem Cells Int, 2016, 2016:7132529.
17
Su N, Gao PL, Wang K, et al. Fibrous scaffolds potentiate the paracrine function of mesenchymal stem cells: a new dimension in cell-material interaction[J]. Biomaterials, 2017, 141:74-85.
18
Carter K, Lee HJ, Na KS, et al. Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo[J]. Acta Biomater, 2019, 99:247-257.
19
Bartosh TJ, Ylostalo JH. Efficacy of 3D culture priming is maintained in human mesenchymal stem cells after extensive expansion of the cells[J]. Cells, 2019, 8(9):1031.
20
Tietze S, Kräter M, Jacobi A, et al. Spheroid culture of mesenchymal stromal cells results in morphorheological properties appropriate for improved microcirculation[J]. Adv Sci (Weinh), 2019, 6(8):1802104.
21
Li Y, Guo G, Li L, et al. Three-dimensional spheroid culture of human umbilical cord mesenchymal stem cells promotes cell yield and stemness maintenance[J]. Cell Tissue Res, 2015, 360(2):297-307.
22
Follin B, Juhl M, Cohen S, et al. Increased paracrine immunomodulatory potential of mesenchymal stromal cells in three-dimensional culture[J]. Tissue Eng Part B Rev, 2016, 22(4):322-329.
23
Ylostalo JH, Bazhanov N, Mohammadipoor A, et al. Production and administration of therapeutic mesenchymal stem/stromal cell (MSC) spheroids primed in 3-D cultures under xeno-free conditions[J]. J Vis Exp, 2017, (121):55126.
24
Bartosh TJ, Ylöstalo JH, Bazhanov N, et al. Dynamic compaction of human mesenchymal stem/precursor cells into spheres self-activates caspase dependent IL1 signaling to enhance secretion of modulators of inflammation and immunity (PGE2, TSG6, and STC1)[J]. Stem Cells, 2013, 31(11):2443-2456.
25
Samsonraj RM, Raghunath M, Nurcombe V, et al. Concise review: multifaceted characterization of human mesenchymal stem cells for use in regenerative medicine[J]. Stem Cells Transl Med, 2017, 6(12):2173-2185.
26
Xu Y, Shi TP, Xu AX, et al. 3D spheroid culture enhances survival and therapeutic capacities of MSCs injected into ischemic kidney[J]. J Cell Mol Med, 2016, 20(7):1203-1213.
27
Rettinger CL, Fourcaudot AB, Hong SJ, et al. In vitro characterization of scaffold-free three-dimensional mesenchymal stem cell aggregates[J]. Cell Tissue Res, 2014, 358(2):395-405.
28
Petrenko y, Syková E, Kubinová S. The therapeutic potential of three-dimensional multipotent mesenchymal stromal cell spheroids[J]. Stem Cell Res Ther, 2017, 8(1):94.
29
Lam AT, Sim EJ, Shekaran, et al. Sub-confluent culture of human mesenchymal stromal cells on biodegradable polycaprolactone mircrocarriers enhances bone healing of rat calvarial defect[J]. Cytotherapy, 2019, 21(6):631-642.
30
Sobacchi C, Erreni M, Strina D et al. 3D bone biomimetic scaffolds for basic and translational studies with mesenchymal stem cells[J]. Int J Mol Sci, 2018, 19(10):3150.
31
Chen L, Wu J, Wu C, et al. Three-dimensional co-culture of peripheral blood-derived mesenchymal stem cells and endothelial progenitor cells for bone regeneration[J]. J Biomed Nanotechnol, 2019, 15(2):248-260.
32
Kim TH, Choi JH, Jun Y, et al. 3D-cultured human placenta-derived mesenchymal stem cell spheroids enhance ovary function by inducing folliculogenesis[J]. Sci Rep, 2018, 8(1):15313.
33
徐竹，诸葛启钊，黄李洁. 干细胞3D支架的研究进展[J]. 中国生物工程杂志, 2017, 37(9):112-117.
34
Yu H, Cauchois G, Louvet N, et al. Comparison of MSCs properties in two different hydrogels. Impact of mechanical properties[J]. Biomed Mater Eng, 2017, 28(s1):S193-S200.
[1] 林昌盛, 战军, 肖雪. 上皮性卵巢癌患者诊疗中基因检测及分子靶向药物治疗[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 505-510.
[2] 全勇, 冉新泽, 胡梦佳, 陈芳, 陈乃成, 廖伟年, 陈默, 申明强, 陈石磊, 王崧, 王军平. 低氧习服在小鼠造血干细胞急性放射损伤修复中的作用观察[J]. 中华损伤与修复杂志(电子版), 2023, 18(04): 293-298.
[3] 张原, 李小龙, 王亚鹏. 胰腺癌中ANGPTL2蛋白与免疫抑制细胞浸润的关系及临床意义[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 145-148.
[4] 唐英俊, 李华娟, 王赛妮, 徐旺, 刘峰, 李羲, 郝新宝, 黄华萍. 人脐带间充质干细胞治疗COPD小鼠及机制分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 476-480.
[5] 李埝, 赵建军, 张建勇, 赵睿桢. hAMSCs调控MAPK信号通路对急性肺损伤AQP1的影响[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 156-163.
[6] 李晔, 何洁, 胡锦秀, 王金祥, 田川, 潘杭, 陈梦蝶, 赵晓娟, 叶丽, 张敏, 潘兴华. 高活性间充质干细胞干预猕猴卵巢衰老的研究[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 210-219.
[7] 龙慧玲, 林蜜, 邵婷. 三维球体间充质干细胞培养技术的研究进展及其应用[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 229-234.
[8] 刘文慧, 吴涛, 张曦. 间充质干细胞联合血小板生成素受体激动剂在异基因造血干细胞移植后血小板恢复中的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 242-246.
[9] 王红敏, 谢云波, 王彦虎, 王福生. 间充质干细胞治疗新冠病毒感染的临床研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 247-256.
[10] 秦富豪, 郑正, 江滨. 间充质干细胞在克罗恩病肛瘘治疗中的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 172-177.
[11] 袁久莉, 刘丹, 李林藜, 刘晋宇. 毛囊间充质干细胞的基础研究及临床应用[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 189-192.
[12] 杨蕴钊, 周诚, 石美涵, 赵静, 白雪源. 人羊水间充质干细胞对膜性肾病大鼠的治疗作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 181-186.
[13] 宋艳琪, 任雪景, 王文娟, 韩秋霞, 续玥, 庄凯婷, 肖拓, 蔡广研. 间充质干细胞对顺铂诱导的小鼠急性肾损伤中细胞铁死亡的作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 187-193.
[14] 陈客宏. 干细胞外泌体防治腹膜透析腹膜纤维化新技术研究[J]. 中华肾病研究电子杂志, 2023, 12(03): 180-180.
[15] 梁宇同, 丁旭, 马国慧, 黄艳红. 间充质干细胞在宫腔粘连治疗中的研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(05): 596-599.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号