骨肉瘤诱导多能干细胞模型的研究进展

doi:10.3877/cma.j.issn.2095-1221.2024.01.005

骨肉瘤是一种罕见的、高度恶性的癌症，其进展迅速且具有高度侵袭性。由于早期阶段缺乏特异性症状而经常被忽视，并且被发现时常常已经转移，导致预后不良。这主要是由于对骨肉瘤发展机制的理解不足以及缺乏能够根除肿瘤的有效治疗方法。鉴于骨肉瘤发病率低，使用肿瘤模型来研究其发病和进展，以及开发新的药物和治疗方法，对于提高患者的生存率至关重要。诱导多能干细胞（iPSCs）可以用来模拟各种疾病。定向重编程和分化策略包含整个癌症的进展，并捕获疾病发病初期最早的分子变化。iPSCs具有患者特异的遗传和表观遗传特性以及分化潜能，为开发个性化癌症治疗提供新的平台。本文将回顾骨肉瘤iPSCs模型的研究进展、特性和应用。

关键词: 骨肉瘤, 肿瘤模型, 诱导多能干细胞, 分子机制

Osteosarcoma, a rare yet highly aggressive malignancy, is characterized by swift progression and potent invasiveness. Its insidious nature, owing to the absence of distinctive early symptoms, often results in late detection and subsequent metastasis, leading to a grim prognosis. The primary factors contributing to this dismal outcome are the inadequate comprehension of the underlying mechanisms of osteosarcoma and the absence of efficacious therapies to eradicate the tumor. Despite its low prevalence, tinvestigating the pathogenesis and progression and developing novel pharmaceuticals and therapeutic approaches via tumor models hold considerable significance in enhancing the survival rates of osteosarcoma patients. Induced pluripotent stem cells (iPSCs) serve as a versatile tool to model many diseases, with directed reprogramming and differentiation strategies encapsulating the entire cancer trajectory and capturing the initial molecular alterations in the disease. Endowed with both patient-specific genetic and epigenetic attributes and differentiation potential, iPSCs offer a novel platform for evolving personalized therapies for cancer patients. This article aims to provide an overview of the research advancements, model attributes, and applications of iPSCs models in osteosarcoma.

Key words: Osteosarcoma, Tumor model, Induced pluripotent stem cells, Molecular mechanisms

表1 体外和体内骨肉瘤模型的优缺点

模型类型		优势	劣势	潜能
体外研究	细胞系	易于培养和维护^[12] 实验重现性好^[18]	不能体现肿瘤异质性缺乏肿瘤微环境相互作用有潜在的遗传变异^[12,18]	药物筛选^[19,20] 毒性评价
	3D模型	模拟肿瘤内的各种微环境，体现肿瘤异质性^[10,21]	培养技术复杂^[22,23] 重现性低耗时长且费用贵	药敏研究^[23,24] 研究癌症干细胞^[25]
体内研究	异种移植鼠模型	保持肿瘤异质性^[26] 个性化程度高	耗时长且成本高^[16] 不可大规模研究涉及复杂的道德问题	药物筛选^[27] 毒性评估治疗研究^[17,28]
	转基因小鼠模型	能够研究肿瘤发生和肿瘤进展^[17] 可用于靶基因的临床前验证	建模周期长，错误率高^[29] 维护成本高过表达^[30]或基因缺失^[31]	模仿人类骨肉瘤遗传学和生物学允许操作特定基因^[32]
	犬类自发模型	具有完整免疫系统的天然骨肉瘤模型^[33] 与人类相似的临床表现和干预措施^[26]	建模用时长、耗费大、影响因素多、肿瘤发生不一致^[34]	在生物学上与人类骨肉瘤相似^[17,26] 转化研究

表1 体外和体内骨肉瘤模型的优缺点

模型类型		优势	劣势	潜能
体外研究	细胞系	易于培养和维护^[12] 实验重现性好^[18]	不能体现肿瘤异质性缺乏肿瘤微环境相互作用有潜在的遗传变异^[12,18]	药物筛选^[19,20] 毒性评价
	3D模型	模拟肿瘤内的各种微环境，体现肿瘤异质性^[10,21]	培养技术复杂^[22,23] 重现性低耗时长且费用贵	药敏研究^[23,24] 研究癌症干细胞^[25]
体内研究	异种移植鼠模型	保持肿瘤异质性^[26] 个性化程度高	耗时长且成本高^[16] 不可大规模研究涉及复杂的道德问题	药物筛选^[27] 毒性评估治疗研究^[17,28]
	转基因小鼠模型	能够研究肿瘤发生和肿瘤进展^[17] 可用于靶基因的临床前验证	建模周期长，错误率高^[29] 维护成本高过表达^[30]或基因缺失^[31]	模仿人类骨肉瘤遗传学和生物学允许操作特定基因^[32]
	犬类自发模型	具有完整免疫系统的天然骨肉瘤模型^[33] 与人类相似的临床表现和干预措施^[26]	建模用时长、耗费大、影响因素多、肿瘤发生不一致^[34]	在生物学上与人类骨肉瘤相似^[17,26] 转化研究

图1 肿瘤细胞重编程iPSCs和癌症进展的概括^[39]注：图中展示肿瘤细胞重编程为iPSCs和癌症进展的概括：1为获取人类癌细胞；2为转录因子OSKM重编程人类癌细胞；3为产生iPSCs；4 ~ 5为诱导分化以产生癌症祖细胞；6为利用癌症祖细胞来研究癌症进展的特征。通过这种方式，晚期人类癌症可以被重编程以重现早期疾病和进展，从而发现标记物、途径和治疗方法

表2 易患骨肉瘤遗传综合征iPSCs模型的研究进展

易患骨肉瘤的遗传综合征	iPSCs模型	突变基因	相关病理机制	参考文献
LFS	已建立	p53	LFS-iPSCs模型揭示了导致骨肉瘤形成的H19下调和SFRP2上调	[43,44,45]
RB	已建立	RB1	异常剪接体机制	[46,47,48]
RTS	已建立	RECQL4	与代谢方式氧化磷酸化相关	[49,50]
RAPA	未见报道	RECQL4	未见报道	/
WS	已建立	WRN	衰老相关	[51]
BS	已建立	BLM	尚不清楚	[53]
DBA	已建立	RPS19或RPL5	核糖体生物合成相关	[54,55]
PDB	已建立	TNFRSF11B	抑制破骨细胞分化相关	[52]

表2 易患骨肉瘤遗传综合征iPSCs模型的研究进展

易患骨肉瘤的遗传综合征	iPSCs模型	突变基因	相关病理机制	参考文献
LFS	已建立	p53	LFS-iPSCs模型揭示了导致骨肉瘤形成的H19下调和SFRP2上调	[43,44,45]
RB	已建立	RB1	异常剪接体机制	[46,47,48]
RTS	已建立	RECQL4	与代谢方式氧化磷酸化相关	[49,50]
RAPA	未见报道	RECQL4	未见报道	/
WS	已建立	WRN	衰老相关	[51]
BS	已建立	BLM	尚不清楚	[53]
DBA	已建立	RPS19或RPL5	核糖体生物合成相关	[54,55]
PDB	已建立	TNFRSF11B	抑制破骨细胞分化相关	[52]

1	Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons[J]. Int J Cancer, 2009, 125(1):229-234.
2	Bian J, Liu Y, Zhao X, et al. Research progress in the mechanism and treatment of osteosarcoma[J]. Chin Med J (Engl), 2023, 136(20):2412-2420.
3	周鹏程. 基于能量代谢相关基因的骨肉瘤分型及机制研究[D]. 吉林大学, 2023.
4	王文剑，姚阳，余文熙，等.1593例骨肉瘤流行病及治疗的回顾性分析[J]. 中华骨科杂志, 2018, 38(18):1097-1107.
5	Lindsey BA, Markel JE, Kleinerman ES. Osteosarcoma overview[J]. Rheumatol Ther, 2017, 4(1):25-43.
6	廖健宏，秦琼. 骨肉瘤发病相关因素的研究进展[J]. 癌症进展, 2020, 18(14):1413-1416, 1423.
7	Arora R D, Shaikh H. Osteogenic sarcoma[M]. Treasure Island (FL): StatPearls Publishing, 2024.
8	陈祉璇,姜亚飞,华莹奇,等.精准医学时代骨肉瘤诊疗的研究进展[J]. 中国肿瘤临床, 2019, 46(17):914-918.
9	曹莉莉,朱岩,樊根涛,等.骨肉瘤的治疗进展[J]. 中国骨与关节杂志, 2020, 9(10):771-778.
10	黄少兵. 3D组织工程建立快速原位骨肉瘤动物模型的实验研究[D]. 南华大学, 2020.
11	Sarker DB, Xue Y, Mahmud F, et al. Interconversion of cancer cells and induced pluripotent stem cells[J]. Cells, 2024, 13(2):125. doi: 10.3390/cells13020125.
12	邹昌业,苏乔,李武国,等.人源骨肉瘤原代细胞的分离及其CDX模型和PDX模型的构建[J]. 骨科临床与研究杂志, 2019, 4(5):286-290.
13	符策岗,曾艳,赵红卫,等. 小鼠骨肉瘤模型构建的关键[J]. 中国比较医学杂志, 2016, 26(1):73-75.
14	符策岗,赵红卫,刘扬,等. 骨肉瘤动物模型新进展[J]. 中国实验动物学报, 2015, 23(2):216-220.
15	廖宇昕,蔡郑东. 骨肉瘤动物模型的构建及其应用现状[J]. 中国骨与关节杂志, 2012, 1(3):300-303, 321.
16	范伟,谭毅,安洪.骨肉瘤动物模型研究概述[J]. 中国实验动物学杂志, 2002, 12(3):186-189.
17	Pu F, Guo H, Shi D, et al. The generation and use of animal models of osteosarcoma in cancer research[J]. Genes Dis, 2024, 11(2):664-674.
18	Gillet JP, Varma S, Gottesman MM. The clinical relevance of cancer cell lines[J]. J Natl Cancer Inst, 2013, 105(7):452-458.
19	张铖.研究骨肉瘤耐药性的实验室模型——P糖蛋白阳性的小鼠骨肉瘤细胞系[J]. 国外医学（创伤与外科基本问题分册）, 1996, (4): 244-245.
20	许小涛,刘先洲. 人骨肉瘤多药耐药细胞模型建立及生物学形状分析[J]. 医药导报, 2004, 23(10):716-718.
21	Zanoni M, Cortesi M, Zamagni A, et al. Modeling neoplastic disease with spheroids and organoids[J]. J Hematol Oncol, 2020, 13(1):97. doi: 10.1186/s13045-020-00931-0.
22	Tan L, Wang Y, Hu X, et al. Advances of osteosarcoma models for drug discovery and precision medicine[J]. Biomolecules, 2023, 13(9):1362. doi: 10.3390/biom13091362.
23	Pavlou M, Shah M, Gikas P, et al. Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model[J]. Acta Biomater, 2019, 96:247-257.
24	Roy M, Alix C, Bouakaz A, et al. Tumor spheroids as model to design acoustically mediated drug therapies: a review[J]. Pharmaceutics, 2023, 15(3):806. doi: 10.3390/pharmaceutics15030806.
25	Ozturk S, Gorgun C, Gokalp S, et al. Development and characterization of cancer stem cell-based tumoroids as an osteosarcoma model[J]. Biotechnol Bioeng, 2020, 117(8):2527-2539.
26	杨澜波,史占军. 骨肉瘤动物模型研究进展[J]. 临床骨科杂志, 2009, 12(5):568-571.
27	Chen F, Zhang Z, Shen R, et al. Generation and characterization of patient-derived xenografts from patients with osteosarcoma[J]. Tissue Cell, 2022, 79:101911. doi: 10.1016/j.tice.2022.101911.
28	Kito F, Oyama R, Sakumoto M, et al. Establishment and characterization of novel patient-derived osteosarcoma xenograft and cell line[J]. In Vitro Cell Dev Biol Anim, 2018, 54(7):528-536.
29	Walkley CR, Qudsi R, Sankaran VG, et al. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease[J]. Genes Dev, 2008, 22(12):1662-1676.
30	Huang P, McKee TD, Jain RK, et al. Green fluorescent protein (GFP)-expressing tumor model derived from a spontaneous osteosarcoma in a vascular endothelial growth factor (VEGF)-GFP transgenic mouse[J]. Comp Med, 2005, 55(3):236-243.
31	Liao N, Koehne T, Tuckermann J, et al. Osteoblast-specific inactivation of p53 results in locally increased bone formation[J]. PLoS One, 2021, 16(11):e249894. doi: 10.1371/journal.pone.0249894.
32	Ferrena A, Wang J, Zhang R, et al. SKP2 knockout in Rb1/p53-deficient mouse models of osteosarcoma induces immune infiltration and drives a transcriptional program with a favorable prognosis[J]. Mol Cancer Ther, 2024, 23(2):223-234.
33	Jarvis S, Koumadoraki E, Madouros N, et al. Non-rodent animal models of osteosarcoma: a review[J]. Cancer Treat Res Commun, 2021, 27:100307. doi: 10.1016/j.ctarc.2021.100307.
34	周光新,赵建宁. 骨肉瘤动物模型研究进展[C]//中国抗癌协会,中华医学会肿瘤学分会.第五届中国肿瘤学术大会暨第七届海峡两岸肿瘤学术会议、国际肿瘤细胞与基因治疗学会会议、第二届中日肿瘤介入治疗学术会议论文集.石家庄, 2008:926-928.
35	Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4):663-676.
36	Liu M, Tu J, Gingold JA, et al. Cancer in a dish: progress using stem cells as a platform for cancer research[J]. Am J Cancer Res, 2018, 8(6):944-954.
37	Zhu D, Kong CSL, Gingold JA. Induced pluripotent stem cells and induced pluripotent cancer cells in cancer disease modeling[J]. Adv Exp Med Biol, 2018, 1119:169-183.
38	Gingold J, Zhou R, Lemischka IR, et al. Modeling cancer with pluripotent stem cells[J]. Trends Cancer, 2016, 2(9):485-494.
39	Kim J, Zaret KS. Reprogramming of human cancer cells to pluripotency for models of cancer progression[J]. EMBO J, 2015, 34(6):739-747.
40	Crespo M, Vilar E, Tsai SY, et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing[J]. Nat Med, 2017, 23(7):878-884.
41	Raya A, Rodríguez-Pizà I, Guenechea G, et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells[J]. Nature, 2009, 460(7251):53-59.
42	Wang P, Na J. Mechanism and methods to induce pluripotency[J]. Protein Cell, 2011, 2(10):792-799.
43	Lee DF, Su J, Kim HS, et al. Modeling familial cancer with induced pluripotent stem cells[J]. Cell, 2015, 161(2):240-254.
44	Zhou R, Xu A, Tu J, et al. Modeling osteosarcoma using Li-Fraumeni syndrome patient-derived induced pluripotent stem cells[J]. J Vis Exp, 2018, (136):57664. doi: 10.3791/57664.
45	Kim H, Yoo S, Zhou R, et al. Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism[J]. Proc Natl Acad Sci U S A, 2018, 115(47):E11128-E11137.
46	Vincent A, Khetan V, Rishi P, et al. Generation of a human induced pluripotent stem cell line (VRFi001-A) from orbital adipose tissue of a bilateral retinoblastoma patient with heterozygous RB1 gene deletion[J]. Stem Cell Res, 2018, 29:42-45.
47	Zeng S, Liu L, Ouyang Q, et al. Generation of induced pluripotent stem cells (iPSCs) from a retinoblastoma patient carrying a c.2663G>A mutation in RB1 gene[J]. Stem Cell Res, 2016, 17(2):208-211.
48	Tu J, Huo Z, Yu Y, et al. Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies[J]. Proc Natl Acad Sci U S A, 2022, 119(16):e2117857119.doi: 10.1073/pnas.2117857119.
49	Jewell BE, Liu M, Lu L, et al. Generation of an induced pluripotent stem cell line from an individual with a heterozygous RECQL4 mutation[J]. Stem Cell Res, 2018, 33:36-40.
50	Jewell BE, Xu A, Zhu D, et al. Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome[J]. PLoS Genet, 2021, 17(12):e1009971. doi: 10.1371/journal.pgen.1009971.
51	Cheung HH, Liu X, Canterel-Thouennon L, et al. Telomerase protects werner syndrome lineage-specific stem cells from premature aging[J]. Stem Cell Reports, 2014, 2(4):534-546.
52	Jeong J, Lee D, Park BC, et al. Establishment of a TNFRSF11B knock-out human induced pluripotent stem cell line (KSCBi002-B-2) via CRISPR/Cas9 system[J]. Stem Cell Res, 2023, 71:103167. doi: 10.1016/j.scr.2023.103167.
53	Gatinois V, Desprat R, Becker F, et al. iPSC line derived from a Bloom syndrome patient retains an increased disease-specific sister-chromatid exchange activity[J]. Stem Cell Res, 2020, 43:101696.doi: 10.1016/j.scr.2019.101696.
54	Garçon L, Ge J, Manjunath SH, et al. Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients[J]. Blood, 2013, 122(6):912-921.
55	Doulatov S, Vo LT, Macari ER, et al. Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors[J]. Sci Transl Med, 2017, 9(376):eaah5645. doi: 10.1126/scitranslmed.aah5645.
56	Pang LK, Pena M, Zhao R, et al. Modeling of osteosarcoma with induced pluripotent stem cells[J]. Stem Cell Res, 2020, 49:102006. doi: 10.1016/j.scr.2020.102006.
57	Lin YH, Jewell BE, Gingold J, et al. Osteosarcoma: molecular pathogenesis and iPSC modeling[J]. Trends Mol Med, 2017, 23(8):737-755.
58	Birch JM, Hartley AL, Tricker KJ, et al. Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families[J]. Cancer Res, 1994, 54(5):1298-1304.
59	Hisada M, Garber JE, Fung CY, et al. Multiple primary cancers in families with Li-Fraumeni syndrome[J]. J Natl Cancer Inst, 1998, 90(8):606-611.
60	Zhou R, Xu A, Gingold J, et al. Li-Fraumeni syndrome disease model: a platform to develop precision cancer therapy targeting oncogenic p53[J]. Trends Pharmacol Sci, 2017, 38(10):908-927.
61	Siitonen HA, Sotkasiira J, Biervliet M, et al. The mutation spectrum in RECQL4 diseases[J]. Eur J Hum Genet, 2009, 17(2):151-158.
62	Broaddus E, Topham A, Singh AD. Survival with retinoblastoma in the USA: 1975-2004[J]. Br J Ophthalmol, 2009, 93(1):24-27.
63	Yu CL, Tucker MA, Abramson DH, et al. Cause-specific mortality in long-term survivors of retinoblastoma[J]. J Natl Cancer Inst, 2009, 101(8):581-591.
64	Wong FL, Boice JD Jr, Abramson DH, et al. Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk[J]. JAMA, 1997, 278(15):1262-1267.
65	Temming P, Arendt M, Viehmann A, et al. Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: a report from the German reference center[J]. Pediatr Blood Cancer, 2017, 64(1):71-80.
66	Gutierrez GM, Kong E, Sabbagh Y, et al. Impaired bone development and increased mesenchymal progenitor cells in calvaria of RB1−/− mice[J]. Proc Natl Acad Sci U S A, 2008, 105(47):18402-18407.
67	Ottaviani G, Jaffe N. The etiology of osteosarcoma[J]. Cancer Treat Res, 2009, 152:15-32.
68	Toguchida J, Ishizaki K, Sasaki MS, et al. Preferential mutation of paternally derived RB gene as the initial event in sporadic osteosarcoma[J]. Nature, 1989, 338(6211):156-158.
69	Lu L, Jin W, Wang LL. RECQ DNA helicases and osteosarcoma[J]. Adv Exp Med Biol, 2020, 58:37-54.
70	Larizza L, Roversi G, Volpi L. Rothmund-Thomson syndrome[J]. Orphanet J Rare Dis, 2010, 5:2.doi: 10.1186/1750-1172-5-2.
71	Lu L, Jin W, Liu H, et al. RECQ DNA helicases and osteosarcoma[J]. Adv Exp Med Biol, 2014, 804:129-145.
72	Wang LL, Gannavarapu A, Kozinetz CA, et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome[J]. J Natl Cancer Inst, 2003, 95(9):669-674.
73	Mehollin-Ray AR, Kozinetz CA, Schlesinger AE, et al. Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status[J]. AJR Am J Roentgenol, 2008, 191(2):W62-W66.
74	Ng AJ, Walia MK, Smeets MF, et al. The DNA helicase recql4 is required for normal osteoblast expansion and osteosarcoma formation[J]. PLoS Genet, 2015, 11(4):e1005160. doi: 10.1371/journal.pgen.1005160.
75	Goto M, Miller RW, Ishikawa Y, et al. Excess of rare cancers in Werner syndrome (adult progeria)[J]. Cancer Epidemiol Biomarkers Prev, 1996, 5(4):239-246.
76	Goto M. Werne's syndrome: from clinics to genetics[J]. Clin Exp Rheumatol, 2000, 18(6):760-766.
77	Cheung H, Rennert OM. Chapter 13-Werner syndrome induced pluripotent stem cells, a study of pathologic aging[M]//Birbrair A. Recent Advances in iPSC Disease Modeling, Volume 1. Academic Press, 2020:275-291.
78	Shimamoto A, Kagawa H, Zensho K, et al. Reprogramming suppresses premature senescence phenotypes of werner syndrome cells and maintains chromosomal stability over long-term culture: e112900[J]. PloS one, 2014, 9(11):e112900. doi: 10.1371/journal.pone.0112900.
79	German J, Sanz MM, Ciocci S, et al. Syndrome-causing mutations of theBLMgene in persons in the Bloom's syndrome registry[J]. Hum Mutat, 2007, 28(8):743-753.
80	Cunniff C, Bassetti JA, Ellis NA. Bloom's syndrome: clinical spectrum, molecular pathogenesis, and cancer predisposition[J]. Mol Syndromol, 2017, 8(1):4-23.
81	Vlachos A, Ball S, Dahl N, et al. Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference[J]. Br J Haematol, 2008, 142(6):859-876.
82	Lipton JM, Federman N, Khabbaze Y, et al. Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry[J]. J Pediatr Hematol Oncol, 2001, 23(1):39-44.
83	Batanian JR, Cavalli LR, Aldosari NM, et al. Evaluation of paediatric osteosarcomas by classic cytogenetic and CGH analyses[J]. Mol Pathol, 2002, 55(6):389-393.
84	Bridge JA. Cytogenetic and molecular cytogenetic techniques in orthopaedic surgery[J]. J Bone Joint Surg Am, 1993, 75(4):606-614.

[1]	蒋鹏飞, 程尼涛. 侵犯左肺及心包的巨大胸壁软骨肉瘤一例[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 296-298.
[2]	刘楚, 张建勇. 以骨肉瘤成分为主的肺癌肉瘤1例并文献复习[J]. 中华肺部疾病杂志(电子版), 2022, 15(05): 762-764.
[3]	谢冰冰, 谢曼婷, 向秋玲. 诱导多能干细胞在遗传性心肌病细胞模型中的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(05): 315-320.
[4]	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.
[5]	刘晓梅, 张露, 刘旭, 梁蝶. 巨噬细胞迁移抑制因子靶向miR-127-3p对人肾癌细胞生物学行为的影响[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(02): 76-83.
[6]	胡敏洁, 王思贤, 王永煜. 人诱导多能干细胞及其在血管相关疾病模型中的应用[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(03): 167-175.
[7]	李卓林, 贾如雪, 吴亚婷, 张胜行, 王水良. 肿瘤转移的分子机制及靶向干预研究新进展[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(01): 51-58.
[8]	王浩年, 孙备, 陈华. 胆管内乳头状肿瘤的诊治策略[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 140-144.
[9]	金玺, 孙康, 郭建, 孔梅. 结直肠癌肝转移发生机制的研究进展[J]. 中华结直肠疾病电子杂志, 2023, 12(02): 163-166.
[10]	姜金玉, 张东蕾, 何伟. 蓝光照射氧化损伤模型在眼部疾病中应用的研究进展[J]. 中华眼科医学杂志(电子版), 2022, 12(03): 168-172.
[11]	汪东生, 吴理达, 顾雨春. 细胞基因疗法在视网膜退行性疾病中的应用和挑战[J]. 中华眼科医学杂志(电子版), 2022, 12(03): 129-133.
[12]	李坚, 陶勇, 郦舒伊, 张小花, 胡勇平. 细胞因子与眼科疾病的研究进展[J]. 中华眼科医学杂志(电子版), 2022, 12(02): 115-119.
[13]	许慧中, 颜庆华, 吴晓宏, 陈军辉, 向定朝. 颅骨Paget's病恶变一例报道并文献复习[J]. 中华神经创伤外科电子杂志, 2022, 08(05): 315-317.
[14]	邱明宪, 康肖, 王磊. LncRNA NEAT1靶向miR-185-5p调控骨肉瘤的机制研究[J]. 中华老年骨科与康复电子杂志, 2023, 09(04): 233-239.
[15]	黄涔, 朱跃坤. 慢传输型便秘分子机制研究及临床应用现状[J]. 中华消化病与影像杂志(电子版), 2024, 14(01): 82-89.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Advances in induced pluripotent stem cell models of osteosarcoma

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Advances in induced pluripotent stem cell models of osteosarcoma