脐带来源的华通氏胶间充质干细胞的分离、特性及应用前景

doi:10.3969/j.issn.1004-616x.2022.03.011

摘要/Abstract

摘要： 间充质干细胞(MSCs)的来源非常广泛。虽然各种组织来源的MSCs生物学特性不尽相同，但在标准培养条件下该类细胞均可以贴壁生长；细胞群体中有 95%以上的细胞表达典型的间充质标记分子，如 CD73、CD90 和 CD105，但缺乏造血标记分子CD14、CD19、CD34、CD45和CD79a的表达；特别是均具有分化为成脂细胞、成骨细胞和成软骨细胞的能力。这些性质是国际细胞治疗协会给出的定义该类细胞的最低标准。脐带间充质干细胞是指来源于新生儿脐带组织中的多能干细胞。目前来看，从脐带不同解剖学部位(区室)获得的MSCs的生物学性质也存在差异，其中从脐带华通氏胶中分离获得的华通氏胶间充质干细胞，在增殖能力、分化潜能、免疫调节能力等方面均明显优于其他区室来源的间充质干细胞，是用于组织器官损伤修复及免疫调节的一种理想的“种子”细胞，被认为具有更好的临床应用前景。本文围绕近年来华通氏胶间充质干细胞的分离建系、增殖特性、分化潜能以及临床应用方面的研究进展进行了综述，其中重点介绍了化学诱导分化方案的建立和优化，认为与通过遗传改变诱导重编程方法相比，化学诱导分化方法具有更好的临床应用潜力。

关键词: 脐带, 华通氏胶, 间充质干细胞, 分化潜能, 分离, 增殖特性

中图分类号:

R329.2+8

丁赛, 张红霞, 朱海英. 脐带来源的华通氏胶间充质干细胞的分离、特性及应用前景[J]. 癌变·畸变·突变, 2022, 34(3): 233-236.

参考文献

[1] SRIRAMULU S, BANERJEE A, DI LIDDO R, et al. Concise review on clinical applications of conditioned medium derived from human umbilical cord-mesenchymal stem cells (UC-MSCs)[J]. Int J Hematol Oncol Stem Cell Res, 2018, 12(3): 230-234.
[2] STEFA\U0144SKA K, O\U017CEGOWSKA K, HUTCHINGS G, et al. Human wharton's jelly-cellular specificity, stemness potency, animal models, and current application in human clinical trials[J]. J Clin Med, 2020, 9(4): 1102.
[3] 李艳琪, 王洪一, 姚尧, 等. 人脐带源间充质干细胞分离培养方法的改进[J]. 中国组织工程研究, 2014, 18(10): 1609-1614.
[4] HENDIJANI F. Explant culture: an advantageous method for isolation of mesenchymal stem cells from human tissues[J]. Cell Prolif, 2017, 50(2): e12334.
[5] 马锡慧, 冯凯, 石炳毅. 人脐带间充质干细胞生物学特性及其研究进展[J]. 中国组织工程研究与临床康复, 2011, 15(32): 6064-6067.
[6] HUA J, GONG J, MENG H, et al. Comparison of different methods for the isolation of mesenchymal stem cells from umbilical cord matrix:proliferation and multilineage differentiation as compared to mesenchymal stem cells from umbilical cord blood and bone marrow[J]. Cell Biol Int, 2013, 38(2): 198-210.
[7] SUBRAMANIAN A, FONG C Y, BISWAS A, et al. Comparative characterization of cells from the various compartments of the human umbilical cord shows that the wharton's jelly compartment provides the best source of clinically utilizable mesenchymal stem cells[J]. PLoS One, 2015, 10(6): e0127992.
[8] 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.
[9] BHARTI D, SHIVAKUMAR S B, PARK J K, et al. Comparative analysis of human Wharton's jelly mesenchymal stem cells derived from different parts of the same umbilical cord[J]. Cell Tissue Res, 2018, 372(1): 51-65.
[10] KARAHUSEYINOGLU S, CINAR O, KILIC E, et al. Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys[J].Stem Cells, 2007, 25(2): 319-331.
[11] VANGSNESS C T Jr, STERNBERG H, HARRIS L. Umbilical cord tissue offers the greatest number of harvestable mesenchymal stem cells for research and clinical application: a literature review of different harvest sites[J]. Arthroscopy, 2015, 31(9): 1836-1843.
[12] SOBOLEWSKI K, BAŃKOWSKI E, CHYCZEWSKI L, et al. Collagen and glycosaminoglycans of wharton's jelly[J]. Biol Neonate, 1997, 71(1):11-21.
[13] AFSHARI A, SHAMDANI S, UZAN G, et al. Different approaches for transformation of mesenchymal stem cells into hepatocyte-like cells[J]. Stem Cell Res Ther, 2020, 11(1): 54.
[14] ZHANG Y N, LIE P C, WEI X. Differentiation of mesenchymal stromal cells derived from umbilical cord Wharton's jelly into hepatocyte-like cells[J]. Cytotherapy, 2009, 11(5): 548-558.
[15] ZHENG G, LIU Y, JING Q, et al. Differentiation of human umbilical cord- derived mesenchymal stem cells into hepatocytes in vitro[J]. Biomed Mater Eng, 2015, 25(1 Suppl): 145-157.
[16] CHAO K C, CHAO K F, FU Y S, et al. Islet-like clusters derived from mesenchymal stem cells in Wharton's Jelly of the human umbilical cord for transplantation to control type 1 diabetes[J]. PLoS One, 2008, 3(1):e1451.
[17] WANG H S, HUNG S C, PENG S T, et al. Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord[J]. Stem Cells, 2004, 22(7): 1330-1337.
[18] CONCONI M T, BURRA P, DI LIDDO R, et al. CD105(+) cells from Wharton's jelly show in vitro and in vivo myogenic differentiative potential[J]. Int J Mol Med, 2006, 18(6): 1089-1096.
[19] WU K H, ZHOU B, LU S H, et al. In vitro and in vivo differentiation of human umbilical cord derived stem cells into endothelial cells[J]. J Cell Biochem, 2007, 100(3): 608-616.
[20] FU Y S, SHIH Y T, CHENG Y C, et al. Transformation of human umbilical mesenchymal cells into neurons in vitro[J]. J Biomed Sci, 2004, 11(5): 652-660.
[21] MITCHELL K E, WEISS M L, MITCHELL B M, et al. Matrix cells from Wharton's jelly form neurons and Glia[J]. Stem Cells, 2003, 21(1): 50-60.
[22] NAN C R, GUO L, ZHAO Z M, et al. Tetramethylpyrazine induces differentiation of human umbilical cord-derived mesenchymal stem cells into neuron-like cells in vitro[J]. Int J Oncol, 2016, 48(6): 2287-2294.
[23] LIANG J, WU S, ZHAO H, et al. Human umbilical cord mesenchymal stem cells derived from Wharton ??s jelly differentiate into cholinergiclike neurons in vitro[J]. Neurosci Lett, 2013, 532: 59-63.
[24] HU Y, LIANG J, CUI H P, et al. Wharton's jelly mesenchymal stem cells differentiate into retinal progenitor cells[J]. Neural Regen Res, 2013, 8(19): 1783-1792.
[25] HUANG P, LIN L M, WU X Y, et al. Differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells into germ-like cells in vitro[J]. J Cell Biochem, 2010, 109(4): 747-754.
[26] DENG Y N, YI S H, WANG G Y, et al. Umbilical cord- derived mesenchymal stem cells instruct dendritic cells to acquire tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1[J]. Stem Cells Dev, 2014, 23(17): 2080-2092.
[27] 胡明智, 张晶莹, 杨国安, 等. miR-1-5p修饰脐带间充质干细胞对系统性红斑狼疮T淋巴细胞亚群的免疫调节[J]. 中国组织工程研究, 2021, 25(31): 4928-4938.
[28] SALEH M, FOTOOK KIAEI S Z, KAVIANPOUR M. Application of Wharton jelly-derived mesenchymal stem cells in patients with pulmonary fibrosis[J]. Stem Cell Res Ther, 2022, 13(1): 71.
[29] GAUTHAMAN K, FONG C Y, SUGANYA C A, et al. Extra-embryonic human Wharton's jelly stem cells do not induce tumorigenesis, unlike human embryonic stem cells[J]. Reprod Biomed Online, 2012, 24(2):235-246.
[30] PALADINO F V, SARDINHA L R, PICCINATO C A, et al. Intrinsic variability present in wharton's jelly mesenchymal stem cells and T cell responses may impact cell therapy[J]. Stem Cells Int, 2017, 2017:8492797.
[31] LUO S, XIAO S, AI Y, et al. Changes in the hepatic differentiation potential of human mesenchymal stem cells aged in vitro[J]. Ann Transl Med, 2021, 9(21): 1628.