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) ›› 2023, Vol. 13 ›› Issue (05) : 288 -298. doi: 10.3877/cma.j.issn.2095-1221.2023.05.005

论著

影响扩张型心肌病干细胞移植疗效的差异miRNA表达分析
范家铭, 杨秭莹†(), 冯振辉, 陈一欢, 王雨桐, 沈振亚†()   
  1. 215006　苏州大学附属第一医院心脏大血管外科
  • 收稿日期:2023-08-26 出版日期:2023-10-01
  • 通信作者: 杨秭莹, 沈振亚
  • 基金资助:
    国家自然科学基金资助项目(92168203); 博习培育计划项目(BXQN2023006，202131); 江苏省科研项目(M2022010, 21KJB310003); 苏州市医学研究项目(SKY2022131，KJXW2021001)

Analysis of differential miRNA expression related to the efficacy of stem cell transplantation in dilated cardiomyopathy

Jiaming Fan, Ziying Yang†(), Zhenhui Feng, Yihuan Chen, Yutong Wang, Zhenya Shen†()   

  1. Department of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University, Suzhou 215006, China
  • Received:2023-08-26 Published:2023-10-01
  • Corresponding author: Ziying Yang, Zhenya Shen
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

范家铭, 杨秭莹, 冯振辉, 陈一欢, 王雨桐, 沈振亚. 影响扩张型心肌病干细胞移植疗效的差异miRNA表达分析[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(05): 288-298.

Jiaming Fan, Ziying Yang, Zhenhui Feng, Yihuan Chen, Yutong Wang, Zhenya Shen. Analysis of differential miRNA expression related to the efficacy of stem cell transplantation in dilated cardiomyopathy[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(05): 288-298.

目的

基于生物信息学分析探索影响扩张型心肌病（DCM）干细胞移植疗效的差异表达微小RNA （miRNAs）及其靶基因。

方法

本研究筛选术前基线特征相似的DCM患者，以干细胞移植术后左心室射血分数改善> 5%为标准，分为治疗良好组和无效组。通过对两组患者的骨髓间充质干细胞样本进行miRNAs高通量测序，运用edgeR筛选出两组间的差异表达miRNAs，并使用MiRanda、TargetScan和RNAhybrid数据库进行靶基因预测，对预测得到的靶基因进行GO、KEGG及Reactome富集分析。使用STRING数据库和Cytoscape软件，并参考紧密度、介数中心性、度三种拓扑分析方法和韦恩图筛选关键基因。两组间比较采用t检验。

结果

本研究共筛选出44个差异表达miRNAs，其中23个上调，21个下调。上调的差异表达miRNAs靶基因有908个，下调的差异表达miRNAs靶基因835个。GO分析结果显示靶基因在生物过程中主要富集在细胞代谢过程的调节，分子功能主要富集在离子结合，细胞组分则主要与细胞膜相关。KEGG通路和Reactome分析发现靶基因主要与调节干细胞多能性的信号通路、RIG-I样受体信号通路和RNA聚合酶II转录等相关。此外，韦恩图共筛选出4个关键基因，分别为MED1、SMAD2、TRAF6、GSK3B，其中GSK3B和TRAF6分别为上调的hsa-miR-1304-3p和下调的hsa-miR-146a-3p靶基因，MED1和SMAD2为下调的hsa-miR-1299靶基因。

结论

本研究提供了hsa-miR-1304-3p、hsa-miR-1299、hsa-miR-146a-3p 3个可能用于提示DCM患者干细胞移植预后的差异表达miRNAs，其调控的关键基因MED1、SMAD2、TRAF6、GSK3B及所在通路可能是提高干细胞移植治疗DCM的潜在作用靶点。

关键词: 扩张型心肌病, 间充质干细胞, MicroRNAs, 基因表达分析
Objective

To identify differentially expressed miRNAs (DEmiRNAs) and their targets that potentially influence the therapeutic efficacy of bone marrow mesenchymal stem cells (BMSCs) transplantation for dilated cardiomyopathy (DCM) .

Methods

The DCM patients with similar baseline characteristics before stem cell transplantation were selected and categorized into two groups based on the improvement of left ventricular ejection fraction after stem cell transplantation, namely response group (improvement > 5%) and nonresponse group (improvement ≤ 5%) . High-throughput sequencing of miRNAs in BMSCs samples from two groups was performed, and DEmiRNAs were analyzed by the edgeR tool. Furthermore, the target genes of DEmiRNAs were predicted by MiRanda, TargetScan, and RNAhybrid tools, and subjected to GO, KEGG, and Reactome enrichment analyses. Finally, utilizing the STRING database and Cytoscape software, three topological analysis methods based on closeness, betweenness, and degree, and the Venn diagram were employed to identify the hub genes.

Results

This study identified 44 DEmiRNAs, including 23 upregulated and 21 downregulated. 908 and 835 genes were predicted as target genes for upregulated and downregulated miRNAs respectively. GO analyses indicated that the target genes were mainly enriched in the regulation of cell metabolism in biological processes (BP) , ion binding in molecular functions (MF) , and cell membrane in cell components (CC) . In addition, KEGG and Reactome pathway analyses discovered signal pathways regulating stem cell pluripotency, RIG-I-like receptor, and RNA polymerase II transcription as the most enriched pathways. Moreover, MED1, SMAD2, TRAF6, and GSK3B were identified as hub genes, and GSK3B and TRAF6 were the target genes of upregulated hsa-miR-1304-3p and downregulated hsa-miR-146a-3p respectively. MED1 and SMAD2 were the target genes of downregulated hsa-miR-1299.

Conclusion

The study predicted three DEmiRNAs that potentially influence the prognosis of DCM patients after stem cell transplantation. The hub genes MED1, SMAD2, TRAF6, and GSK3B and related signaling pathways regulated by DEmiRNAs are potential targets to improve the therapeutic efficacy of stem cell transplantation for DCM.

Key words: Dilated cardiomyopathy, Mesenchymal stem cells, MicroRNAs, Gene expression profiling
表1 DCM志愿者的基线数据
  治疗良好组（n = 3） 无效组（n = 3） P值
术前LVEF （%） 23.67 ± 6.35 31.00 ± 12.12 0.406
收缩压（mmHg） 118.00 ± 31.43 115.67 ± 5.13 0.905
舒张压（mmHg） 71.33 ± 33.29 74.00 ± 8.72 0.900
年龄（岁） 52.33 ± 19.01 25.00 ± 13.00 0.109
体重（kg） 71.00 ± 38.74 80.67 ± 38.55 0.775
白细胞计数（109/L） 5.03 ± 1.38 8.06 ± 1.95 0.093
淋巴细胞比例 35.83 ± 4.38 36.67 ± 4.70 0.833
单核细胞比例 9.07 ± 1.99 6.17 ± 1.29 0.101
中性粒细胞比例 51.90 ± 3.16 53.40 ± 5.17 0.690
血红蛋白（g/L） 128.67 ± 27.61 142.33 ± 3.22 0.442
血小板计数（109/L） 151.33 ± 27.61 216.67 ± 48.09 0.111
血小板分布宽度（%） 15.70 ± 0.44 16.17 ± 0.35 0.222
谷丙转氨酶（U/L） 27.53 ± 19.23 29.83 ± 7.37 0.856
谷草转氨酶（U/L） 23.50 ± 5.11 20.23 ± 5.69 0.500
肌酐（μmol/l） 107.80 ± 60.51 72.27 ± 12.58 0.376
尿酸（μmol/L） 541.57 ± 151.19 397.60 ± 108.65 0.252
空腹血糖（mmol/L） 5.91 ± 0.72 5.01 ± 0.30 0.115
甘油三酯（mmol/L） 1.86 ± 1.04 1.56 ±1.27 0.764
高密度脂蛋白（mmol/L） 0.97 ± 0.19 1.02 ± 0.21 0.787
肌酸激酶（U/L） 62.77 ± 35.37 152.23 ± 124.00 0.296
肌钙蛋白T（ng/mL） 25.43 ± 21.05 30.32 ± 18.03 0.775
国际标准化比值 1.03 ± 0.29 0.99 ± 0.64 0.381
活化部分凝血酶时间（s） 34.00 ± 0.80 36.17 ± 3.74 0.383
凝血酶时间（s） 16.50 ± 0.79 15.63 ± 0.90 0.281
纤维蛋白原（g/L） 3.03 ± 0.42 3.05 ± 0.54 0.955
C反应蛋白（mg/L） 2.07 ± 1.98 1.58 ±1.48 0.749
用药情况 呋塞米、螺内酯、地高辛等常规缓解用药 呋塞米、螺内酯、地高辛等常规缓解用药 /
图1 治疗良好组与无效组之间的差异miRNAs注：a图为差异miRNAs数量柱状图；b图为差异miRNAs火山图，展示了miRNAs差异程度；c图为差异程度排名前20个miRNAs的雷达图，外圈黑色数字为log2 FC值，黄色和蓝色圈分别表示基因为上调或下调，圈的大小根据差异程度大小而变化，红、绿色数字代表在不同组别中的平均表达量，内圈不规则形状为表达量丰度
图2 差异miRNAs聚类热图注：红色为高表达量，绿色为低表达量
表2 显著上调DEmiRNAs （Top10）
序号 miRNA log2 FC P值
1 hsa-miR-1304-3p 7.732179 0.003302
2 hsa-miR-3130-5p 6.373648 0.005818
3 hsa-miR-4709-5p 4.776981 0.043042
4 hsa-miR-490-3p 4.08839 0.000911
5 hsa-miR-3690 4.029446 0.011437
6 hsa-miR-451a 4.011799 0.006003
7 hsa-miR-150-5p 3.758931 0.006093
8 hsa-miR-204-5p 3.736849 0.000195
9 hsa-miR-1247-5p 3.683972 0.000854
10 hsa-miR-133a-3p 3.673588 0.000011
表3 显著下调DEmiRNAs （Top10）
序号 miRNA log2FC P值
1 hsa-miR-3664-3p -5.422009 0.007567
2 hsa-miR-1299 -4.405587 0.00007
3 hsa-miR-302a-5p -4.030619 0.003616
4 hsa-miR-146a-3p -3.554035 0.004336
5 hsa-miR-3679-5p -3.527034 0.014498
6 hsa-miR-410-5p -3.376326 0.00433
7 hsa-miR-138-1-3p -3.324536 0.004222
8 hsa-miR-541-3p -3.199355 0.01913
9 hsa-miR-302b-3p -2.914008 0.006077
10 hsa-miR-1197 -2.712633 0.00005
图3 差异miRNAs靶基因GO富集分析注：a图为上调差异miRNAs靶基因的GO富集生物过程，横坐标为靶基因富集到当前通路中的数量/该物种富集到当前通路中的数量，纵坐标为每一个气泡所代表的GO term，气泡的大小代表该term所包含的基因数目，气泡颜色代表富集显著程度；b图为上调差异miRNAs靶基因的GO富集分子功能；c图为上调差异miRNAs靶基因的GO富集细胞组分；d图为下调差异miRNAs靶基因的GO富集生物过程；e图为下调差异miRNAs靶基因的GO富集分子功能；f图为下调差异miRNAs靶基因的GO富集细胞组分
图4 差异miRNAs靶基因KEGG通路富集分析注：a图为上调差异miRNAs靶基因KEGG通路富集图，每个柱子代表一个Pathway，柱子长短代表富集在该通路的靶基因占有KEGG注释信息的基因数百分比，颜色为富集显著程度；b图为下调差异miRNAs靶基因KEGG通路富集图
图5 差异miRNAs靶基因Reactome富集分析注：a图为上调差异miRNAs靶基因Reactome富集图，最外圈为富集前10的Pathway ID，圈外为基因数目的标尺，第二圈为背景基因中该Pathway的数目以及Q值，基因越多条形越长，Q值越小颜色越红，第三圈为富集到该通路的靶基因数目，内圈为各Pathway中靶基因数量除以该通路中背景基因数量的Rich Factor值；b图为下调差异miRNAs靶基因Reactome富集图
图6 PPI网络图注：每一个靶基因圆的大小、颜色深浅均代表度值，越靠近内圈度值越高，线条越粗表示蛋白间相互作用越强
图7 Hub基因的鉴定注：a图为三种拓扑分析方式筛选出的结果韦恩图；b图为hub基因及其连接的第1个节点PPI网络，圈越大度值越高，连接2个圈的线粗细代表蛋白间相互作用强弱
图8 差异miRNAs与hub基因的靶向调控关系注：a图为上调差异miRNAs与其所调控hub基因之间的调控关系，圈的大小代表节点的连通性强弱，线条粗细表示结合位点匹配得分值的大小；b图为下调差异miRNAs与其所调控hub基因之间的调控关系
表4 Cytohubba中的三种拓扑分析排名前10的靶基因结果
排序 度 紧密度 介数中心性
1 TRAF6 TRAF6 TRAF6
2 SMAD2 MAPK9 MAPK9
3 GSK3B STAT3 MED1
4 MED1 GSK3B SMAD2
5 STAT3 SMAD2 GSK3B
6 RPL4 MED1 ITGA1
7 XPO1 HNF4A SORBS1
8 MRPL22 NPM1 DCTN1
9 FMR1 RAF1 FLNA
10 RPS17 NR3C1 FMR1
表5 DEmiRNA调控的4个hub基因
基因 中文描述 DEmiRNA DEmiRNA上/下调
MED1 介导体复合物亚基1 hsa-miR-1299 下调
SMAD2 SMAD家族成员2 hsa-miR-1299 下调
GSK3B 糖原合酶激酶3β hsa-miR-1304-3p 上调
TRAF6 TNF受体相关因子6 hsa-miR-146a-3p 下调
1
中华医学会心血管病学分会，中国心肌炎心肌病协作组. 中国扩张型心肌病诊断和治疗指南[J]. 临床心血管病杂志, 2018, 34(5): 421-434.
2
Weintraub RG, Semsarian C, Macdonald P. Dilated cardiomyopathy[J]. Lancet, 2017, 390(10092):400-414.
3
Japp AG, Gulati A, Cook SA, et al. The diagnosis and evaluation of dilated cardiomyopathy[J]. J Am Coll Cardiol, 2016, 67(25):2996-3010.
4
Wei X, Yang X, Han ZP, et al. Mesenchymal stem cells: a new trend for cell therapy[J]. Acta Pharmacol Sin, 2013, 34(6):747-754.
5
Chin SP, Poey AC, Wong CY, et al. Intramyocardial and intracoronary autologous bone marrow-derived mesenchymal stromal cell treatment in chronic severe dilated cardiomyopathy[J]. Cytotherapy, 2011, 13(7):814-821.
6
Argüero R, Careaga-Reyna G, Castaño-Guerra R, et al. Cellular autotransplantation for ischemic and idiopathic dilated cardiomyopathy. Preliminary report[J]. Arch Med Res, 2006, 37(8):1010-1014.
7
Diaz-Navarro R, Urrútia G, Cleland JG, et al. Stem cell therapy for dilated cardiomyopathy[J]. Cochrane Database Syst Rev, 2021, 7(7): CD013433. doi: 10.1002/14651858.CD013433.pub2.
8
中华医学会组织修复与再生分会心脏再生学组. 自体干细胞移植治疗心力衰竭中国专家共识（2022）[J]. 中华医学杂志, 2023, 103(18):1376-1385.
9
Bartel DP. MicroRNAs: target recognition and regulatory functions[J]. Cell, 2009, 136(2):215-233.
10
陈玲玲,冯珊珊,范祖森, 等. 非编码RNA研究进展[J]. 中国科学:生命科学, 2019, 49(12):1573-1605.
11
Hare JM, DiFede DL, Rieger AC, et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM Trial[J]. J Am Coll Cardiol, 2017, 69(5):526-537.
12
Hu S, Liu S, Zheng Z, et al. Isolated coronary artery bypass graft combined with bone marrow mononuclear cells delivered through a graft vessel for patients with previous myocardial infarction and chronic heart failure: a single-center, randomized, double-blind, placebo-controlled clinical trial[J]. J Am Coll Cardiol, 2011, 57(24):2409-2415.
13
邓保平，郑俊猛，梁毅，等. 扩张型心肌病临床特征及心脏病理分析[J].岭南心血管病杂志，2018，24(1):83-86.
14
Segers VF, Lee RT. Stem-cell therapy for cardiac disease[J]. Nature, 2008, 451(7181):937-942.
15
Clevers H, Loh KM, Nusse R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control[J]. Science, 2014, 346(6205):1248012. doi: 10.1126/science.1248012.
16
Reya T, Clevers H. Wnt signaling in stem cells and cancer[J]. Nature, 2005, 434(7035): 843-850.
17
Okita K, Yamanaka S. Intracellular signaling pathways regulating pluripotency of embryonic stem cells[J]. Curr Stem Cell Res Ther, 2006, 1(1):103-111.
18
Zhang Y, Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer[J]. J Hematol Oncol, 2020, 13(1):165. doi: 10.1186/s13045-020-00990-3.
19
Sato N, Meijer L, Skaltsounis L, et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor[J]. Nat Med, 2004, 10(1):55-63.
20
Hirotani S, Zhai P, Tomita H, et al. Inhibition of glycogen synthase kinase 3beta during heart failure is protective[J]. Circ Res, 2007, 101(11):1164-1174.
21
Zhu W, Yang L, Du Z. Layered functional network analysis of gene expression in human heart failure[J]. PLoS One, 2009, 4(7):e6288. doi: 10.1371/journal.pone.0006288.
22
de Carvalho JB, de Morais GL, Vieira TCDS, et al. miRNA genetic variants alter their secondary structure and expression in patients with RASopathies syndromes[J]. Front Genet, 2019, 10:1144. doi: 10.3389/fgene.2019.01144.
23
Brown KA, Pietenpol JA, Moses HL. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling[J]. J Cell Biochem, 2007, 101(1):9-33.
24
Li Y, Yang S, Liu Y, et al. IFT20 governs mesenchymal stem cell fate through positively regulating TGF-β-Smad2/3-Glut1 signaling mediated glucose metabolism[J]. Redox Biol, 2022, 54:102373. doi: 10.1016/j.redox.2022.102373.
25
Zhai H, Fesler A, Ba Y, et al. Inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy[J]. Oncotarget, 2015, 6(23):19735-19746.
26
孟雪梅，刘思桦，常胜，等. miR-1299在食管癌中的表达及其对食管癌细胞迁移和侵袭的影响[J]. 肿瘤, 2019, 39(8):623-631.
27
Cordero-Reyes AM, Youker K, Estep JD, et al. Molecular and cellular correlates of cardiac function in end-stage DCM: a study using speckle tracking echocardiography[J]. JACC Cardiovasc Imaging, 2014, 7(5):441-452.
28
Soutourina J. Transcription regulation by the Mediator complex[J]. Nat Rev Mol Cell Biol, 2018, 19(4):262-274.
29
Fatima M, Gao J, Han T, et al. MED1 deficiency in macrophages aggravates isoproterenol-induced cardiac fibrosis in mice[J]. Am J Pathol, 2022, 192(7):1016-1027.
30
Wang C, Xing Y, Zhang J, et al. MED1 regulates BMP/TGF-β in endothelium: implication for pulmonary hypertension[J]. Circ Res, 2022, 131(10):828-841.
31
Xu M, Liu PP, Li H. Innate immune signaling and its role in metabolic and cardiovascular diseases[J]. Physiol Rev, 2019, 99(1):893-948.
32
Onomoto K, Onoguchi K, Yoneyama M. Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors[J]. Cell Mol Immunol, 2021, 18(3):539-555.
33
Wei X, Zhang A, Yang W, et al. Depletion of β3-adrenergic receptor relieves pressure overload-induced cardiac hypertrophy and heart failure via enhancing innate immune response[J]. Biomed Pharmacother, 2021, 143:112194. doi: 10.1016/j.biopha.2021.112194.
34
Allen IC, Moore CB, Schneider M, et al. NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-I-MAVS and TRAF6-NF-κB signaling pathways[J]. Immunity, 2011, 34(6):854-865.
35
Walsh MC, Lee J, Choi Y. Tumor necrosis factor receptor-associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system[J]. Immunol Rev, 2015, 266(1):72-92.
36
Yang Y, Li L. Depleting microRNA-146a-3p attenuates lipopolysaccharide-induced acute lung injury via up-regulating SIRT1 and mediating NF-κB pathway[J]. J Drug Target, 2021, 29(4):420-429.
37
Yeh JN, Sung PH, Chiang JY, et al. Early treatment with combination of SS31 and entresto effectively preserved the heart function in doxorubicin-induced dilated cardiomyopathic rat[J]. Biomed Pharmacother, 2021, 141:111886. doi: 10.1016/j.biopha.2021.111886.
38
Salama H, Zekri AR, Medhat E, et al. Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease[J]. Stem Cell Res Ther, 2014, 5(3):70. doi: 10.1186/scrt459.
39
Izadi M, Sadr Hashemi Nejad A, Moazenchi M, et al. Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial[J]. Stem Cell Res Ther, 2022, 13(1):264. doi: 10.1186/s13287-022-02941-w.
40
Garaycoechea JI, Crossan GP, Langevin F, et al. Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells[J]. Nature, 2018, 553(7687):171-177.
41
Harrell CR, Volarevic A, Djonov VG, et al. Mesenchymal stem cell: a friend or foe in anti-tumor immunity[J]. Int J Mol Sci, 2021, 22(22):12429. doi: 10.3390/ijms222212429.
[1] 沈纵, 魏晨如, 朱邦晖, 包郁露, 伍国胜, 孙瑜. 间充质干细胞治疗吸入性损伤的动物实验研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(02): 180-183.
[2] 邓瑞锋, 程璐, 周宇林, 刘远灵, 江文聪, 江敏耀, 江福能, 习明. TGF-β1诱导骨髓间充质干细胞外泌体分泌miR-424-3p促进前列腺癌细胞增殖及转移[J]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(01): 82-89.
[3] 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.
[4] 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.
[5] 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.
[6] 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.
[7] 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.
[8] 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.
[9] 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.
[10] 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.
[11] 刘远, 张马莉, 高鹏, 曾塬杰, 王靖. 肩峰下滑囊在肩袖损伤修复中的研究进展[J]. 中华肩肘外科电子杂志, 2023, 11(04): 377-381.
[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