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) ›› 2022, Vol. 12 ›› Issue (01) : 34 -38. doi: 10.3877/cma.j.issn.2095-1221.2022.01.006

综述

间充质干细胞促进脐带血干细胞体外扩增的研究进展
李华1, 李晓帆2, 李乃农2,†()   
  1. 1. 350001　福州，福建医科大学附属协和医院造血干细胞移植中心　福建省血液病研究所　福建省血液病重点实验室　福建省恶性血液病临床医学研究中心；361021　厦门医学院附属第二医院科教部
    2. 350001　福州，福建医科大学附属协和医院造血干细胞移植中心　福建省血液病研究所　福建省血液病重点实验室　福建省恶性血液病临床医学研究中心
  • 收稿日期:2021-06-30 出版日期:2022-02-01
  • 通信作者: 李乃农
  • 基金资助:
    国家自然科学基金(81270641，81541024，81200400); 厦门市科技局指导性项目(3502Z20179008)

Research advances ofumbilical cord blood stem cells proliferation promoted by mesenchymal stem cells in vitro

Hua Li1, Xiaofan Li2, Nainong Li2,†()   

  1. 1. Hematopoietic Stem Cell Transplantation Center, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Clinical Research Center for hematological malignancies of Fujian province, Fujian Medical University Union Hospital, Fuzhou 350001, China; Department of Science and Education, The Second Affiliated Hospital of Xiamen Medical college, Xiamen 361021, China
    2. Hematopoietic Stem Cell Transplantation Center, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Clinical Research Center for hematological malignancies of Fujian province, Fujian Medical University Union Hospital, Fuzhou 350001, China
  • Received:2021-06-30 Published:2022-02-01
  • Corresponding author: Nainong Li
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

李华, 李晓帆, 李乃农. 间充质干细胞促进脐带血干细胞体外扩增的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(01): 34-38.

Hua Li, Xiaofan Li, Nainong Li. Research advances ofumbilical cord blood stem cells proliferation promoted by mesenchymal stem cells in vitro[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(01): 34-38.

非亲缘脐带血移植是治疗造血系统疾病的重要移植方式之一，但脐带血移植面临的最大挑战是造血干细胞（HSCs）数量不足，特别是成人患者受到脐带血干细胞数量的限制，导致造血及免疫恢复延迟，非复发死亡率升高。体外扩增脐带血HSCs （UCB-HSCs）是解决该问题的途径之一。研究发现可以通过模拟骨髓造血龛（niche）这一生态位使HSCs在体外进行自我更新增殖，而间充质干细胞（MSCs）正是造血龛的重要的组成细胞之一。本文将探讨MSCs在UCB-HSCs体外扩增中的应用。重点以MSCs促造血的特点、机制，促进脐带血干细胞增殖的各种策略以及其临床应用和前景做一综述。

关键词: 间充质干细胞, 脐带血造血干细胞, 体外扩增

Umbilical cord blood transplantation (UCBT) is one of the most important transplantation in treating hematological disorders. The biggest challenge in UCBT is the insufficient number of hematopoietic stem cells (HSCs) , especially in adult patients limited by the number of stem cells from umbilical cord blood, which leads to delayed hematopoietic and immune recovery and increases the risk of infection and early transplant-related death. In vitro expansion of umbilical cord blood HSCs (UCB-HSCs) is one of the ways to solve this problem. Studies have found that HSCs could be self-renewalin vitro by mimetic hematopoietic niches in bone marrow. Mesenchymal stem cells (MSCs) play an important role in niche. In this review, we will discuss the application of MSCs in UCB-HSCs expansion in vitro, focusing on characteristics and mechanisms of hematopoiesis promoted by MSCs, strategies of promoting the proliferation of umbilical cord blood stem cells. Clinical applications and development prospect are also reviewed.

Key words: Mesenchymal stem cells, Umbilical cord blood-hematopoietic stem cells, In vitro expansion
1
Shouval R, Fein JA, Labopin M, et al. Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis[J]. Lancet Haematol, 2019, 6(11):e573-e584.
2
Barker JN, Kurtzberg J, Ballen K, et al. Optimal practices in unrelated donor cord blood transplantation for hematologic malignancies[J]. Biol Blood Marrow Transplant, 2017, 23(6):882-896.
3
Rocha V, Wagner JE Jr, Sobocinski KA, et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources[J]. N Engl J Med, 2000, 342(25):1846-1854.
4
Mehta RS, Dave H, Bollard CM, et al. Engineering cord blood to improve engraftment after cord blood transplant[J]. Stem Cell Investig, 2017, 4:41.
5
Dehn J, Spellman S, Hurley CK, et al. Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR[J]. Blood, 2019, 134(12):924-934.
6
Ghafouri-Fard S, Niazi V, Taheri M, et al. Effect of small molecule on ex vivo expansion of cord blood hematopoietic stem cells: A concise review[J]. Front Cell Dev Biol, 2021, 9:649115.doi: 10.3389/fcell.2021.649115.
7
Kadekar D, Kale V, Limaye L. Differential ability of MSCs isolated from placenta and cord as feeders for supporting ex vivo expansion of umbilical cord blood derived CD34(+) cells[J]. Stem Cell Res Ther, 2015, 6:201.doi: 10.1186/s13287-015-0194-y.
8
Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses[J]. Exp Hematol, 2000, 28(8):875-884.
9
Mendez-Ferrer S, Michurina TV, Ferraro F, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche[J]. Nature, 2010, 466(7308):829-834.
10
Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells[J]. Science, 2009, 324(5935):1673-1677.
11
Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells[J]. Nature, 2014, 505(7483):327-334.
12
Szade K, Gulati GS, Chan CKF, et al. Where hematopoietic stem cells live: the bone marrow niche[J]. Antioxid Redox Signal, 2018, 29(2):191-204.
13
Rendra E, Scaccia E, Bieback K. Recent advances in understanding mesenchymal stromal cells[J]. F1000Res, 2020, 9:F1000 Faculty Rev-156. doi:10.12688/f1000research.21862.1.
14
Friedenstein AJ. Stromal mechanisms of bone marrow: cloning in vitro and retransplantation in vivo[J]. Haematol Blood Transfus, 1980, 25:19-29.
15
Klein C, Strobel J, Zingsem J, et al. Ex vivo expansion of hematopoietic stem- and progenitor cells from cord blood in coculture with mesenchymal stroma cells from amnion, chorion, Wharton's jelly, amniotic fluid, cord blood, and bone marrow[J]. Tissue Eng Part A, 2013, 19(23-24):2577-2585.
16
Orticelli V, Papait A, Vertua E, et al. Human amniotic mesenchymal stromal cells support the ex vivo expansion of cord blood hematopoietic stem cells[J]. Stem Cells Transl Med, 2021, 10(11):1516-1529.
17
Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement[J]. Cytotherapy, 2006, 8(4):315-317.
18
Stik G, Crequit S, Petit L, et al. Extracellular vesicles of stromal origin target and support hematopoietic stem and progenitor cells[J]. J Cell Biol, 2017, 216(7):2217-2230.
19
Zhang Y, Chai C, Jiang XS, et al. Co-culture of umbilical cord blood CD34+ cells with human mesenchymal stem cells[J]. Tissue Eng, 2006, 12(8):2161-2170.
20
Lu LL, Liu YJ, Yang SG, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials[J]. Haematologica, 2006, 91(8):1017-1026.
21
Friedman R, Betancur M, Boissel L, et al. Umbilical cord mesenchymal stem cells: adjuvants for human cell transplantation[J]. Biol Blood Marrow Transplant, 2007, 13(12):1477-1486.
22
Szydlak R. Biological, chemical and mechanical factors regulating migration and homing of mesenchymal stem cells[J]. World J Stem Cells, 2021, 13(6):619-631.
23
Su G, Liu L, Yang L, et al. Homing of endogenous bone marrow mesenchymal stem cells to rat infarcted myocardium via ultrasound-mediated recombinant SDF-1alpha adenovirus in microbubbles[J]. Oncotarget, 2018, 9(1):477-487.
24
Frenette PS, Pinho S, Lucas D, et al. Mesenchymal stem cell: keystone of the hematopoietic stem cell niche and a stepping-stone for regenerative medicine[J]. Annu Rev Immunol, 2013, 31:285-316.
25
石蕊，徐曼，苏永峰，等. Notch信号介导共培养脐带间充质干细胞和造血干细胞的相互作用[J]. 细胞与分子免疫学杂志, 2012, 28(8):793-796.
26
Kim A, Shim S, Kim MJ, et al. Mesenchymal stem cell-mediated Notch2 activation overcomes radiation-induced injury of the hematopoietic system[J]. Sci Rep, 2018, 8(1):9277.doi:10.1038/s41598-018-27666-w.
27
Lo Iacono M, Russo E, Anzalone R, et al. Wharton's Jelly mesenchymal stromal cells support the expansion of cord blood-derived CD34(+) cells mimicking a hematopoietic niche in a direct cell-cell contact culture system[J]. Cell Transplant, 2018, 27(1):117-129.
28
Batsali AK, Pontikoglou C, Koutroulakis D, et al. Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton's jelly and bone marrow-derived mesenchymal stem cells[J]. Stem Cell Res Ther, 2017, 8(1):102.doi:10.1186/s13287-017-0555-9.
29
Kadereit S, Deeds LS, Haynesworth SE, et al. Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34(+)/CD38(-) early progenitors cultured over human MSCs as a feeder layer[J]. Stem Cells, 2002, 20(6):573-582.
30
Wang JF, Wang LJ, Wu YF, et al. Mesenchymal stem/progenitor cells in human umbilical cord blood as support for ex vivo expansion of CD34(+) hematopoietic stem cells and for chondrogenic differentiation[J]. Haematologica, 2004, 89(7):837-844.
31
Lin HD, Fong CY, Biswas A, et al. Allogeneic human umbilical cord Wharton's jelly stem cells increase several-fold the expansion of human cord blood CD34+ cells both in vitro and in vivo[J]. Stem Cell Res Ther, 2020, 11(1):527.
32
Li Q, Zhao D, Chen Q, et al. Wharton's jelly mesenchymal stem cell-based or umbilical vein endothelial cell-based serum-free coculture with cytokines supports the ex vivo expansion/maintenance of cord blood hematopoietic stem/progenitor cells[J]. Stem Cell Res Ther, 2019, 10(1):376.
33
Oubari F, Amirizade N, Mohammadpour H, et al. The important role of FLT3-L in ex vivo expansion of hematopoietic stem cells following co-culture with mesenchymal stem cells[J]. Cell J, 2015, 17(2):201-210.
34
Ferreira MS, Jahnen-Dechent W, Labude N, et al. Cord blood-hematopoietic stem cell expansion in 3D fibrin scaffolds with stromal support[J]. Biomaterials, 2012, 33(29):6987-6997.
35
Huang X, Zhu B, Wang X, et al. Three-dimensional co-culture of mesenchymal stromal cells and differentiated osteoblasts on human bio-derived bone scaffolds supports active multi-lineage hematopoiesis in vitro: functional implication of the biomimetic HSC niche[J]. Int J Mol Med, 2016, 38(4):1141-1151.
36
Darvish M, Payandeh Z, Soleimanifar F, et al. Umbilical cord blood mesenchymal stem cells application in hematopoietic stem cells expansion on nanofiber three-dimensional scaffold[J]. J Cell Biochem, 2019, 25. doi:10.1002/jcb.28487.
37
Tavakol DN, Tratwal J, Bonini F, et al. Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis[J]. Biomaterials, 2020, 232:119665.doi:10.1016/j.biomaterials.2019.119665.
38
Futrega K, Atkinson K, Lott WB, et al. Spheroid coculture of hematopoietic stem/progenitor cells and monolayer expanded mesenchymal stem/stromal cells in polydimethylsiloxane microwells modestly improves in vitro hematopoietic stem/progenitor cell expansion[J]. Tissue Eng Part C Methods, 2017, 23(4):200-218.
39
Thery C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines[J]. J Extracell Vesicles, 2018, 7(1):1535750.doi:10.1080/20013078.2018.1535750.
40
Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of exosome composition[J]. Cell, 2019, 177(2):428-445.e418.
41
Borger V, Bremer M, Ferrer-Tur R, et al. Mesenchymal stem/stromal cell-derived extracellular vesicles and their potential as novel immunomodulatory therapeutic agents[J]. Int J Mol Sci, 2017, 18(7):1450. doi:10.3390/ijms18071450.
42
Abels ER, Breakefield XO. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake[J]. Cell Mol Neurobiol, 2016, 36(3):301-312.
43
Abreu SC, Lopes-Pacheco M, Weiss DJ, et al. Mesenchymal stromal cell-derived extracellular vesicles in lung diseases: current status and perspectives[J]. Front Cell Dev Biol, 2021, 9:600711.doi:10.3389/fcell.2021.600711.
44
Ghebes CA, Morhayim J, Kleijer M, et al. Extracellular vesicles derived from adult and fetal bone marrow mesenchymal stromal cells differentially promote ex vivo expansion of hematopoietic stem and progenitor cells[J]. Front Bioeng Biotechnol, 2021, 9:640419.doi: 10.3389/fbioe.2021.640419.
45
Xie H, Sun L, Zhang L, et al. Mesenchymal stem cell-derived microvesicles support ex vivo expansion of cord blood-derived CD34(+) cells[J]. Stem Cells Int, 2016, 2016:6493241.doi: 10.1155/2016/6493241.
46
Pashoutan Sarvar D, Karimi MH, Movassaghpour A, et al. The effect of mesenchymal stem cell-derived microvesicles on erythroid differentiation of umbilical cord blood-derived CD34(+) Cells[J]. Adv Pharm Bull, 2018, 8(2):291-296.
47
Aqmasheh S, Shamsasenjan K, Khalaf Adeli E, et al. Effect of mesenchymal stem cell-derived microvesicles on megakaryocytic differentiation of CD34(+) hematopoietic stem cells[J]. Adv Pharm Bull, 2020, 10(2):315-322.
48
Jalnapurkar S, Moirangthem RD, Singh S, et al. Microvesicles secreted by nitric oxide-primed mesenchymal stromal cells boost the engraftment potential of hematopoietic stem cells[J]. Stem Cells, 2019, 37(1):128-138.
49
Chen T, Zhang P, Fan W, et al. Co-transplantation with mesenchymal stem cells expressing a SDF-1/HOXB4 fusion protein markedly improves hematopoietic stem cell engraftment and hematogenesis in irradiated mice[J]. Am J Transl Res, 2014, 6(6):691-702.
50
Ajami M, Soleimani M, Abroun S, Atashi A. Comparison of cord blood CD34+ stem cell expansion in coculture with mesenchymal stem cells overexpressing SDF-1 and soluble /membrane isoforms of SCF[J]. J Cell Biochem, 2019, 120(9):15297-15309.
51
Chen W, Li M, Su G, et al. Co-transplantation of hematopoietic stem cells and Cxcr4 gene-transduced mesenchymal stem cells promotes hematopoiesis[J]. Cell Biochem Biophys, 2015, 71(3):1579-1587.
52
Kiani AA, Abdi J, Halabian R, et al. Over expression of HIF-1alpha in human mesenchymal stem cells increases their supportive functions for hematopoietic stem cells in an experimental co-culture model[J]. Hematology, 2014, 19(2):85-98.
53
Arai F, Suda T. Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche. Ann N Y Acad Sci. 2007, 1106:41-53.
54
Galan-Diez M, Kousteni S. The osteoblastic niche in hematopoiesis and hematological myeloid malignancies[J]. Curr Mol Biol Rep, 2017, 3(2):53-62.
55
Barreto-Duran E, Mejia-Cruz CC, Jaramillo-Garcia LF, et al. 3D multicellular spheroid for the study of human hematopoietic stem cells: synergistic effect between oxygen levels, mesenchymal stromal cells and endothelial cells[J]. J Blood Med, 2021, 12:517-528.
56
Teixeira FG, Salgado AJ. Mesenchymal stem cells secretome: current trends and future challenges[J]. Neural Regen Res, 2020, 15(1):75-77.
57
Romanov YA, Volgina NE, Balashova EE, et al. Human umbilical cord mesenchymal stromal cells support viability of umbilical cord blood hematopoietic stem cells but not the "Stemness" of their progeny in co-culture[J]. Bull Exp Biol Med, 2017, 163(4):523-527.
58
de Lima M, McNiece I, Robinson SN, et al. Cord-blood engraftment with ex vivo mesenchymal-cell coculture[J]. N Engl J Med, 2012, 367(24):2305-2315.
59
Mehta RS, Saliba RM, Cao K, et al. Ex Vivo mesenchymal precursor cell-expanded cord blood transplantation after reduced-intensity conditioning regimens improves time to neutrophil recovery[J]. Biol Blood Marrow Transplant, 2017, 23(8):1359-1366.
60
Congrains A, Bianco J, Rosa RG, et al. 3D scaffolds to model the hematopoietic stem cell niche: applications and perspectives[J]. Materials (Basel), 2021, 14(3):569. doi:10.3390/ma14030569.
[1] 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.
[2] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 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.
[7] 崔燕妮, 任颜, 梁凤婷, 覃艳红, 王宏伟. 脐带血源性产品Omidubicel的临床研发进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 178-182.
[8] 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.
[9] 陈玉婷, 周影, 陆雅斐, 江滨. 缺氧预处理间充质干细胞的功能及机制研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(02): 115-120.
[10] 符莞孟, 王晓黎, 刘玉, 张潍, 张菊. 干细胞治疗多囊卵巢综合征的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(02): 108-114.
[11] 雷双银, 习剑鑫, 贺羽轩, 姚静宜, 石博雅, 马杰, 池光范, 李美英. 间充质干细胞源外泌体在神经退行性疾病治疗中的应用与进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(02): 93-100.
[12] 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.
[13] 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.
[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