肺成体干细胞体外培养模型的研究进展
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国家重点研发计划(2018YFD0900603)


Advances of in vitro culture models derived from lung adult stem cells
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    摘要:

    目前,肺体外培养模型有肺类器官和肺芯片两种主要手段。肺类器官是离体的肺上皮干细胞在体外特定的三维培养环境中生长,自发形成具有自我更新能力的干细胞簇并成功分化出功能细胞。肺芯片是利用人工活性膜为细胞提供组织分层结构,模拟微环境和机械力的仿生微流体芯片。由于原有二维培养模式缺乏精确的微结构和功能,组织体外培养模型作为模拟肺部发育、稳态、损伤和再生机制的研究工具,为肺部纤维化、癌症等疾病的探索提供了新的手段和可能。本文就肺成体干细胞两种体外培养模型的分类、研发历史、建立方法、实际应用、优缺点等方面进行综述,期望为器官移植和再生、药物筛选等应用提供参考。

    Abstract:

    Due to the lack of precise microstructure and functions of the two-dimensional culture model, the in vitro culture models of lung organoids and lung-on-chips, as two main research tools to mimic lung development, homeostasis, injury, and regeneration, allow further exploration of pulmonary fibrosis, lung cancer, and other diseases. Lung organoid refers to isolated lung epithelial stem cells growing in a three-dimensional environment in vitro to form mini-clusters of cells that self-renew, self-reorganize, and differentiate into functional cell types. Based on the microfluidic chip technology, lung-on-chips use porous flexible membrane made of poly to provide tissue-layered structures for cells and simulate microenvironment and mechanical forces. We reviewed the classification, research and development history, establishment methods, practical applications, advantages and disadvantages of two main in vitro culture models derived from lung adult stem cells, hoping to provide a reference for organ transplantation and regeneration and drug screening.

    参考文献
    [1] Tata PR, Rajagopal J. Plasticity in the lung:making and breaking cell identity. Development, 2017, 144(5):755-766.
    [2] Wang YX, Tang N. The diversity of adult lung epithelial stem cells and their niche in homeostasis and regeneration. Sci China Life Sci, 2021, 64(12):2045-2059.
    [3] Corrò C, Novellasdemunt L, Li VSW. A brief history of organoids. Am J Physiol Cell Physiol, 2020, 319(1):C151-C165.
    [4] Aros CJ, Pantoja CJ, Gomperts BN. Wnt signaling in lung development, regeneration, and disease progression. Commun Biol, 2021, 4(1):601.
    [5] Ferretti R, Baldassarre A, Billy E, et al. Tumor cell invasion into Matrigel:optimized protocol for RNA extraction. BioTechniques, 2021, 70(6):327-335.
    [6] Wu QR, Liu JF, Wang XH, et al. Organ-on-a-chip:recent breakthroughs and future prospects. Biomed Eng Online, 2020, 19(1):9.
    [7] Huh D, Matthews BD, Mammoto A, et al. Reconstituting organ-level lung functions on a chip. Science, 2010, 328(5986):1662-1668.
    [8] Nawroth JC, Barrile R, Conegliano D, et al. Stem cell-based Lung-on-Chips:the best of both worlds? Adv Drug Deliv Rev, 2019, 140:12-32.
    [9] Shrestha J, Razavi Bazaz S, Aboulkheyr Es H, et al. Lung-on-a-chip:the future of respiratory disease models and pharmacological studies. Crit Rev Biotechnol, 2020, 40(2):213-230.
    [10] 陈镜龙. 肺上皮干细胞研究进展. 国际儿科学杂志, 2020, 47(4):239-243. Chen JL. Advances in lung epithelial stem cells. Int J Pediatr, 2020, 47(4):239-243(in Chinese).
    [11] Jacob A, Vedaie M, Roberts DA, et al. Derivation of self-renewing lung alveolar epithelial type Ⅱ cells from human pluripotent stem cells. Nat Protoc, 2019, 14(12):3303-3332.
    [12] Rock JR, Onaitis MW, Rawlins EL, et al. Basal cells as stem cells of the mouse Trachea and human airway epithelium. PNAS, 2009, 106(31):12771-12775.
    [13] Van Der Velden JL, Wagner DE, Lahue KG, et al. TGF-β1-induced deposition of provisional extracellular matrix by tracheal basal cells promotes epithelial- to-mesenchymal transition in a c-Jun NH2-terminal kinase-1-dependent manner. Am J Physiol Lung Cell Mol Physiol, 2018, 314(6):L984-L997.
    [14] Evans MJ, Van Winkle LS, Fanucchi MV, et al. Cellular and molecular characteristics of basal cells in airway epithelium. Exp Lung Res, 2001, 27(5):401-415.
    [15] Morrisey EE. Basal cells in lung development and repair. Dev Cell, 2018, 44(6):653-654.
    [16] McGraw MD, Kim SY, Reed C, et al. Airway basal cell injury after acute diacetyl (2,3-butanedione) vapor exposure. Toxicol Lett, 2020, 325:25-33.
    [17] Bilodeau C, Shojaie S, Goltsis O, et al. TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds. NPJ Regen Med, 2021, 6(1):12.
    [18] Rock JR, Onaitis MW, Rawlins EL, et al. Basal cells as stem cells of the mouse Trachea and human airway epithelium. PNAS, 2009, 106(31):12771-12775.
    [19] You YJ, Richer EJ, Huang T, et al. Growth and differentiation of mouse tracheal epithelial cells:selection of a proliferative population. Am J Physiol Lung Cell Mol Physiol, 2002, 283(6):L1315-L1321.
    [20] Tadokoro T, Wang Y, Barak LS, et al. IL-6/STAT3 promotes regeneration of airway ciliated cells from basal stem cells. PNAS, 2014, 111(35):E3641-E3649.
    [21] Tata PR, Mou HM, Pardo-Saganta A, et al. Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature, 2013, 503(7475):218-223.
    [22] Danahay H, Pessotti AD, Coote J, et al. Notch2 is required for inflammatory cytokine-driven goblet cell Metaplasia in the lung. Cell Rep, 2015, 10(2):239-252.
    [23] Rock JR, Gao X, Xue Y, et al. Notch-dependent differentiation of adult airway basal stem cells. Cell Stem Cell, 2011, 8(6):639-648.
    [24] Suzuki T, Ito Y, Sakai Y, et al. Generation of human bronchial organoids for SARS-CoV-2 research. bioRxiv, 2020.
    [25] Reynolds SD, Malkinson AM. Clara cell:progenitor for the bronchiolar epithelium. Int J Biochem Cell Biol, 2010, 42(1):1-4.
    [26] Rokicki W, Rokicki M, Wojtacha J, et al. The role and importance of club cells (Clara cells) in the pathogenesis of some respiratory diseases. Kardiochir Torakochirurgia Pol, 2016, 13(1):26-30.
    [27] Guha A, Deshpande A, Jain A, et al. Uroplakin 3a+ cells are a distinctive population of epithelial progenitors that contribute to airway maintenance and post-injury repair. Cell Rep, 2017, 19(2):246-254.
    [28] McQualter JL, Yuen KR, Williams B, et al. Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung. PNAS, 2010, 107(4):1414-1419.
    [29] Lee JH, Tammela T, Hofree M, et al. Anatomically and functionally distinct lung mesenchymal populations marked by Lgr5 and Lgr6. Cell, 2017, 170(6):1149-1163.e12.
    [30] Li J, Wang Z, Chu QQ, et al. The strength of mechanical forces determines the differentiation of alveolar epithelial cells. Dev Cell, 2018, 44(3):297-312.e5.
    [31] Wang YJ, Tang Z, Huang HW, et al. Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate. PNAS, 2018, 115(10):2407-2412.
    [32] Chen Q, Liu YR. Heterogeneous groups of alveolar type Ⅱ cells in lung homeostasis and repair. Am J Physiol Cell Physiol, 2020, 319(6):C991-C996.
    [33] Nabhan AN, Brownfield DG, Harbury PB, et al. Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells. Science, 2018, 359(6380):1118-1123.
    [34] Barkauskas CE, Cronce MJ, Rackley CR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest, 2013, 123(7):3025-3036.
    [35] Shiraishi K, Shichino S, Ueha S, et al. Mesenchymal-epithelial interactome analysis reveals essential factors required for fibroblast-free alveolosphere formation. iScience, 2019, 11:318-333.
    [36] Youk J, Kim T, Evans KV, et al. Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2. Cell Stem Cell, 2020, 27(6):905-919.e10.
    [37] Kathiriya JJ, Wang CQ, Zhou MQ, et al. Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells. Nat Cell Biol, 2022, 24(1):10-23.
    [38] Kobayashi Y, Tata A, Konkimalla A, et al. Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis. Nat Cell Biol, 2020, 22(8):934-946.
    [39] Delorey TM, Ziegler CGK, Heimberg G, et al. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature, 2021, 595(7865):107-113.
    [40] Verheyden JM, Sun X. A transitional stem cell state in the lung. Nat Cell Biol, 2020, 22(9):1025-1026.
    [41] Co JY, Margalef-Català M, Li XN, et al. Controlling epithelial polarity:a human enteroid model for host-pathogen interactions. Cell Rep, 2019, 26(9):2509-2520.e4.
    [brosis. Nat Commun, 2020, 11(1):3559.
    [65] Basil MC, Katzen J, Engler AE, et al. The cellular and physiological basis for lung repair and regeneration:past, present, and future. Cell Stem Cell, 2020, 26(4):482-502.
    [66] Shi RS, Radulovich N, Ng C, et al. Organoid cultures as preclinical models of non-small cell lung cancer. Clin Cancer Res, 2020, 26(5):1162-1174.
    [67] Dost AFM, Moye AL, Vedaie M, et al. Organoids model transcriptional hallmarks of oncogenic KRAS activation in lung epithelial progenitor cells. Cell Stem Cell, 2020, 27(4):663-678.e8.ipotent stem cells residing at the bronchioalveolar- duct junction. Nat Genet, 2019, 51(4):728-738.
    [46] Zuo W, Zhang T, Wu DZ, et al. p63+Krt5+ distal airway stem cells are essential for lung regeneration. Nature, 2015, 517(7536):616-620.
    [47] Zacharias WJ, Frank DB, Zepp JA, et al. Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor. Nature, 2018, 555(7695):251-255.
    [48] Vaughan AE, Brumwell AN, Xi Y, et al. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature, 2015, 517(7536):621-625.
    [49] Kathiriya JJ, Brumwell AN, Jackson JR, et al. Distinct airway epithelial stem cells hide among club cells but mobilize to promote alveolar regeneration. Cell Stem Cell, 2020, 26(3):346-358.e4.
    [50] Huh D, Kim HJ, Fraser JP, et al. Microfabrication of human organs-on-chips. Nat Protoc, 2013, 8(11):2135-2157.
    [51] Douville NJ, Zamankhan P, Tung YC, et al. Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model. Lab Chip, 2011, 11(4):609-619.
    [52] Huh D, Leslie DC, Matthews BD, et al. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci Transl Med, 2012, 4(159):159ra147.
    [53] Jain A, Barrile R, Van Der Meer AD, et al. Primary human lung alveolus-on-a-chip model of intravascular thrombosis for assessment of therapeutics. Clin Pharmacol Ther, 2018, 103(2):332-340.
    [54] Felder M, Trueeb B, Stucki AO, et al. Impaired wound healing of alveolar lung epithelial cells in a breathing lung-on-a-chip. Front Bioeng Biotechnol, 2019, 7:3.
    [55] Huh D, Fujioka H, Tung YC, et al. Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems. PNAS, 2007, 104(48):18886-18891.
    [56] Sellgren KL, Butala EJ, Gilmour BP, et al. A biomimetic multicellular model of the airways using primary human cells. Lab Chip, 2014, 14(17):3349-3358.
    [57] Nesmith AP, Agarwal A, McCain ML, et al. Human airway musculature on a chip:an in vitro model of allergic asthmatic bronchoconstriction and bronchodilation. Lab Chip, 2014, 14(20):3925-3936.
    [58] Benam KH, Novak R, Nawroth J, et al. Matched- comparative modeling of normal and diseased human airway responses using a microengineered breathing lung chip. Cell Syst, 2016, 3(5):456-466.e4.
    [59] 魏昕钰, 李明虓, 张灵倩, 等. 用于代谢气体分析的化学改性微流控肺泡芯片. 传感器与微系统, 2021, 40(6):20-23. Wei XY, Li MX, Zhang LQ, et al. Chemical modified alveolus-on-a-chip microfluidic device for metabolites gas analysis. Transducer Microsyst Technol, 2021, 40(6):20-23(in Chinese).
    [60] Song JW, Paek J, Park KT, et al. A bioinspired microfluidic model of liquid plug-induced mechanical airway injury. Biomicrofluidics, 2018, 12(4):042211.
    [61] Hassell BA, Goyal G, Lee E, et al. Human organ chip models recapitulate orthotopic lung cancer growth, therapeutic responses, and tumor dormancy in vitro. Cell Rep, 2017, 21(2):508-516.
    [62] Si LL, Bai HQ, Rodas M, et al. Human organs-on-chips as tools for repurposing approved drugs as potential influenza and COVID19 therapeutics in viral pandemics. bioRxiv, 2020.
    [63] Chen YW, Huang SX, De Carvalho ALRT, et al. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biol, 2017, 19(5):542-549.
    [64] Strunz M, Simon LM, Ansari M, et al. Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fi
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李童,杨劲树,杨卫军. 肺成体干细胞体外培养模型的研究进展[J]. 生物工程学报, 2022, 38(9): 3255-3266

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  • 收稿日期:2022-01-11
  • 录用日期:2022-03-22
  • 在线发布日期: 2022-09-24
  • 出版日期: 2022-09-25
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