Introduction
The applications of ncRNAs in tissue engineering
Neural tissue engineering
Tab.1 ncRNAs with potential applications for tissue engineering. |
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 [31–33]; 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 [66–68] miR-199a-5p, siRNA-SMARCA4, siRNA-MST1 [69] |
Hepatocytes Promote proliferation | miR-21 [70–72]; 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 [83–86] 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 [95–97] |
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 [123–125] |
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] |
Neural stem cells
Neuronal cells
Neuroglial cells
Liver tissue engineering
Skin tissue engineering
Muscle tissue engineering
Vascular tissue engineering
Application methods

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. |