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Engineering    2017, Vol. 3 Issue (1) : 3-15     https://doi.org/10.1016/J.ENG.2017.01.005
Research |
非编码RNA 及其在组织工程中的潜在应用
李石营,钱天梅,王星辉,刘杰,顾晓松()
Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China
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摘要 

组织工程是医学科学中一个相对较新但发展迅速的领域。非编码RNA(ncRNA) 是不编码蛋白质的功能性RNA 分子,它们可以调节细胞的行为、改变组织的生物学环境。虽然以对ncRNA 作为治疗靶点尚未进入临床实践,但ncRNA 在组织工程中的应用已经吸引了越来越多的关注,而且对ncRNA 的调节作用和释放方法的深入探讨可以促进其在组织工程中的应用。本文简要介绍了ncRNA 在神经、皮肤、肝脏、血管和肌肉的调控作用和可能的释放方法及其潜在的治疗应用价值。

关键词 组织工程非编码RNA(ncRNA)microRNA(miRNA)神经皮肤肝脏血管系统肌肉    
Abstract

Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs (ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering. The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.

Keywords Tissue engineering      Noncoding RNAs      MicroRNAs      Nerve      Skin      Liver      Vascular system      Muscle     
基金资助: 
通讯作者: 顾晓松     E-mail: nervegu@ntu.edu.cn
最新录用日期:    在线预览日期:    发布日期: 2017-03-02
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Shiying Li
Tianmei Qian
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引用本文:   
Shiying Li,Tianmei Qian,Xinghui Wang, et al. Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering[J]. Engineering, 2017, 3(1): 3-15.
网址:  
http://engineering.org.cn/EN/10.1016/J.ENG.2017.01.005     OR     http://engineering.org.cn/EN/Y2017/V3/I1/3
Cell type and function ncRNAs
Nerve
Neural stem/progenitor cells
Promote proliferation
miR-25 [12]; miR-137 [13]; miR-184 [14]; miR-195 [15]
Induce differentiation miR-9, siRNA-TLX [16]; let-7d [17]; miR-137 [13]; miR-184 [14]; miR-195 [15]; miR-34a [18];
lncRNA-BDNF-AS, siRNA-BDNF-AS [19]
Mesenchymal stem cells
Induce differentiation
miR-9 [20]; miR-124 [21]
Reduce differentiation miR-128 [22]
Neuronal cells
Inhibit cell death
miR-223 [23]; miR-181c [24]; miR-592 [25]; miR-424 [26]; miR-23a-3p [27]; miR-23a/b, miR-27a/b, siRNA-Apaf-1 [28]
Promote cell death miR-134 [29]; miR-200c [30]; miR-30a/b [3133]; miR-124 [34]; miR-711 [35]
Regulate degeneration and apoptosis miR-20a [36]; miR-29b [37]; miR-146a, siRNA-miR146a [38]
Promote neurite outgrowth miR-7 [39]; miR-21 [40]; miR-222, siRNA-PTEN [41]; miR-8 [42]; miR-431 [43]; miR-145 [44]; lncRNA-uc.217 [45]; miR-138, siRNA-SIRT1 [46]
Microglial cells
Inhibit inflammation
let-7c [47]; miR-124, siRNA-C/EBP-α [48]
Promote pro-inflammation miR-155 [49]
Inhibit activation let-7c-5p [50]
Astrocytes
Promote proliferation
miR-17-5p [51]
Inhibit inflammation miR-146a [52]
Promote activation and differentiation miR-181 [24]
Inhibit proliferation and migration lncRNA-SCIR1 [53]
Schwann cells
Inhibit proliferation and migration miR-182 [54]; let-7 [55]; miR-1 [56]
Promote proliferation and migration miR-221, miR-222 [57]
Inhibit migration miR-9 [58]
Promote migration miR-132 [59]
Regulate dedifferentiation and proliferation miR-34a [60]
Regulate myelination miR-140 [60]; miR-29a [61]
Regulate fibrinolysis miR-340 [62]
Liver
Stem/progenitor cells
Reduce differentiation
Induce differentiation
Induce/reduce differentiation
Reduce differentiation and engraftment
let-7b [63]; let-7f [64]
miR-1246, miR-1290, miR-148a, miR-30a, miR-30a, miR-424 [65]
miR-122, siRNA-FoxA1 [6668]
miR-199a-5p, siRNA-SMARCA4, siRNA-MST1 [69]
Hepatocytes
Promote proliferation
miR-21 [7072]; miR-211 [73]; lncRNA-URHC [74]
Inhibit proliferation miR-26a [75]; miR-33 [76]; miR-127, siRNA-Bcl6 [77]; miR-378 [70]; lncRNA-H19 [78]
Regulate cholesterol metabolism lncRNA-HC [79]
Promote migration lncRNA-HOTAIR [80]
Inhibit apoptosis and inflammation lncRNA-TUG1 [81]
Cholangiocytes
Inhibit cell function
miR-506 [82]
Skin
Epithelial stem cells
Inhibit proliferation, induce differentiation
Induce differentiation
miR-203 [8386]
miR-27b, miR-224 [87]; miR-574-3p, miR-31 [88]
Inhibit proliferation miR-34, siRNA-P63 [89]; miR-720 [90]; miR-210, siRNA-E2F3 [91]
Improve proliferation, reduce differentiation miR-125b, siRNA-FGFR2 [92,93]
Inhibit proliferation, induce differentiation miR-24, siRNA-PAK4 [94]
Keratinocytes
Improve migration
miR-205 [9597]
Inhibit migration, improve proliferation miR-483-3p [98]
Inhibit migration miR-198 [99]
Improve migration, inhibit migration miR-21 [100,101]
Improve migration and proliferation miR-31, siRNA-EMP-1, siRNA-TGF-β [102]
Regulate apoptosis lncRNA-p21 [103]
Fibroblasts
Inhibit proliferation
let-7, miR-125 [104]
Improve proliferation miR-29 [104]; miR-21 [105]; miR-22 [106]; lncRNA-H19 [107]
Induce senescence miR-152, miR-181a [108]; miR-141 [109]; miR-143 [110]; miR-519a [111]
Improve migration miR-21 [112]
Induce epithelial–mesenchymal transition miR-34 [113]; let-7 [114]
Reduce epithelial–mesenchymal transition miR-200 [113]
Reduce transdifferentiation miR-146a [115,116]; miR-7 [117]
Decrease extracellular matrix deposition miR-29 [118,119]; miR-150 [120]; miR-19a [121]
Increase extracellular matrix deposition miR-92a [122]
Increase mechano-transduction miR-21 [123125]
Control collagen stabilization lncRNA-TSIX, siRNA-TSIX [126]
Melanocytes
Inhibit apoptosis
miR-17 [127,128]
Muscle
Myoblasts
Induce differentiation
Promote proliferation
Promote proliferation and reduce differentiation
Reduce differentiation
Promote proliferation and migration
lncRNA-MD1 [129]; miR-1 [130]; lncRNA-MyoD [131]; lncRNA-Dum [132]; lncRNA-MUNC [133];?lncRNA-YY1 [134]; miR-29 [135]; miR-181 [136];?lncRNA-H19 [137]; miR-322, miR-503 [138]
miR-133 [130]
lncRNA-sirt1?AS [139]; lncRNA-Malat1 [31,140]; lncRNA-31 [141]
miR-23a, siRNA-Myh [77]
miR-486 [142]
Skeletal muscle satellite cells
Induce differentiation
Inhibit proliferation and induce differentiation
miR-206 [143]; miR-214, siRNA-Ezh2 [144]; miR-27b [145]
miR-1, miR-206 [146]
Skeletal muscle stem cells
Inhibit differentiation
Induce cell-cycle arrest
miR-669a/q [147]
miR-195, miR-497 [148]
Cardiac progenitor cells
Control the balance between differentiation and proliferation
Inhibit proliferation and induce differentiation
Enhance cardiac remodeling and reduce survival
Inhibit apoptosis
miR-1 [149]
miR-133a [150]; miR-1, miR-499 [151]
miR-208a [152,153]; miR-28b [154]
miR-138 [155]
Cardiomyocytes
Inhibit apoptosis
Regulate differentiation and remodeling
Promote hypertrophy
Promote muscle growth
Induce proliferation
Inhibit hypertrophy
Promote apoptosis
miR-21 [156]; miR-214 [157]; miR-24 [52]; lncRNA-MHRT [158]
miR-21, miR-129, miR-212 [159]
miR-22 [160]
miR-486 [142]
miR-199a, miR-590 [161]; miR-17-92 [162]
lncRNA-H19 [163]
lncRNA-NRF [164]
Cardiac fibroblasts
Inhibit proliferation
Promote proliferation
Induce reprogramming to cardiomyocytes
miR-101 [165]
lncRNA-H19 [166]
miR-1, miR-133, miR-208, miR-499 [167]
Vascular
Endothelial cells
Inhibit proliferation
Promote proliferation and/or migration
Induce senescence and reduce angiogenesis
Inhibit migration and angiogenesis
Promote angiogenesis
Promote apoptosis and senescence
Inhibit proliferation, migration, and apoptosis
Regulate inflammation
miR-34a [168]; miR-19a [169]; miR-200c, siRNA-ZEB1 [170]
miR-126-5p [171]; miR-210 [172]; miR-424 [173]; lncRNA-H19 [81]
miR-34a [168]; miR-217 [174]; miR-17-92 [175]; miR-503 [176]; siRNA-ROBO4 [177]
miR-101, siRNA-EZH2 [178]
miR-17-5p, miR-18a, miR-31, miR-155 [179]; miR-210 [172]; miR-424 [173]; lncRNA-H19 [81]; miR-126 [180]
miR-200c, siRNA-ZEB1 [170]; PINC [181]
miR-503 [176]; miR-155, siRNA-RhoA, siRNA-MYLK [182]
miR-92a, siRNA-KLF4 [183]; miR-663 [184]; miR-10a [185]; miR-712, miR-502, siRNA-TIMP3, siRNA-RECK [186]
Smooth muscle cells
Induce differentiation and inhibit proliferation
Inhibit proliferation, migration, and apoptosis
Promote migration
Promote proliferation
Promote proliferation and inhibit apoptosis
Inhibit proliferation and promote apoptosis
Reduce elastin levels
Regulate phenotype
miR-143, miR-145 [187]; lncRNA-MYOSLID [166]
miR-503 [176]
miR-712, miR-502, siRNA-TIMP3, siRNA-RECK [186]; miR-24, siRNA-Trb3 [188]
miR-24, siRNA-Trb3 [188]; miR-221, miR-222, siRNA-Kip1, siRNA-Kip2 [189]; miR-34a [190]
miR-21 [191]
lncRNA-HIF1A-AS1 [33]; lncRNA-p21 [192]
miR-29a [193]
siRNA-Jagged1 [194]
Fibroblasts
Reduce elastin levels
miR-29a [193]
Stem cells
Induce differentiation
Reduce differentiation
miR-145 [195]; miR-200c, miR-150, siRNA-ZEB1 [196]; miR-1 [197]; miR-10a [198]
siRNA-NOX4, siRNA-TGF-β [199]
Endothelial progenitor cells
Inhibit survival and migration
miR-15a, miR-16 [200]
Tab.1  ncRNAs with potential applications for tissue engineering.
Fig.1  Schematic illustration of ncRNA delivery. (a) Viral transduction of ncRNAs into cells through virus infection using different viral vectors; (b) non-viral transduction through: liposomes; polymers including polyethylene glycol (PEG), poly(lactide-co-glycolide) (PLGA), and polyethylenimine (PEI); chemical modification; or nanoparticles; by which ncRNAs are taken into cells, mainly by cell endocytosis with the help of the above carriers; (c) scaffold-mediated delivery, in which ncRNAs are released into cells from a scaffold loaded with non-viral ncRNA vectors, followed by matrix degradation to enable cell ingrowth.
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