TABLE 1.
USC-based therapies for various diseases of bodily systems.
| Disease | Model | Mechanism | Observations | |
|---|---|---|---|---|
| Renal diseases | Chronic kidney disease | Chronic kidney disease (CKD) rat models | Antioxidative stress and antifibrotic activity | Reduced degrees of glomerular sclerosis and atrophic renal tubules, improved SCr and GFR Zhang et al. (2020a) |
| Renal transplantation | USC | Decreased SSEA4 levels and gradual upregulation of kidney differentiation-related markers | Assessment of renal cell-lineage differentiation ability Choi et al. (2017) | |
| Acute kidney injury | Rat models of ischaemic AKI | USC-based treatment | Upregulated levels of interleukin-10 and TGF-β1, downregulated levels of interferon-γ and IL-1β Tian et al. (2017) | |
| Models of cisplatin-induced AKI | USC treatment in vivo; coculture of cisplatin-induced NRK-52E cells with USCs in vitro | Reduced BUN and SCr levels; higher cell viability and a lower apoptosis in vitro Sun et al. (2019) | ||
| Diabetic nephropathy | STZ-induced rat models | USC-Exo treatment | Increased urine volume and albumin, downregulation of the podocyte survival factor BMP-7 Jiang et al. (2016) | |
| Podocytes treated with USC-Exos | Synergistic effect of USC-Exos and microRNA-16-5p | Protects podocytes via VEGFA Duan et al. (2019) | ||
| Renal tissues | USC-targeted treatment | Reduced levels of BUN and SCr, improved fibrous hyperplasia, reduced expression of α-SMA Xiong et al. (2020) | ||
| Bladder diseases | Bladder reconstruction | Partial cystectomy rat model | Heparin-immobilized basic fibroblast growth factor-loaded scaffolds | Elevated bladder capacity, compliance or decreased inflammation and tissue regeneration Lee et al. (2015) |
| Overactive bladder | Large conductance voltage and Ca2+-activated K+ (BK) channels in USCs | Overexpression of BK channels in USCs | The BK channel antagonist iberiotoxin increased the apoptosis of USCs; USC apoptosis was decreased by treatment with the BK agonist NS1619 Wang et al. (2017b) | |
| Underactive bladder | Preliminary ICC-LC-like phenotype of USCs | Differentiation of USCs into ICC-LCs by the transfection of lentiviral vectors with exogenous gene modifications | Higher c-Kit expression, an automatic depolarization current Sun et al. (2020) | |
| Urethral diseases | Stress urinary incontinence | Mice | Injection of USCs, microbeads and the collagen gel-type 1 | Improved myogenic differentiation, enhanced revascularization and innervation, tissue regeneration Liu et al. (2013) |
| SUI rat models | Treatment of USC-Exos with phosphorylated extracellular-regulated protein kinases | Improved urodynamic parameters, recovered pubococcygeus muscle tissue Wu et al. (2019) | ||
| Urinary tract reconstruction | USCs; tissue-engineered grafts | Induction of media with components such as TGF-β1 and miR-199a-5p | Differentiation of USCs into urothelial and functional contractile smooth muscles Zhao et al. (2019) | |
| Urethral defect rabbit models | Seeding of USCs onto the small intestinal submucosa | Ameliorated urethral calibres, sped up urothelial regeneration, increased smooth muscle content Liu et al. (2017b) | ||
| USCs from healthy adults | Induction of USC differentiation into urothelial cells | Structures phenotypically and functionally comparable to those of the native urothelium Wan et al. (2018) | ||
| USCs from rabbits | Exposure to PDGF-BB and TGF-β1 | High expression of α-SMA and urothelial-specific proteins (AE1/AE3 and E-cadherin) Yang et al. (2018) | ||
| Diabetes | USCs | Conversion to insulin-producing cells | High mRNA levels of the pancreatic transcription factors Pdx1, insulin and glucagon Hwang et al. (2019) | |
| Transplanted USCs from mice that were injected with high-dose STZ | USC transplantation to promote islet vascular regeneration | Improved glucose tolerance and islet morphology, enhanced insulin content, improved blood glucose Zhao et al. (2018) | ||
| Type II diabetic rats | Tail vein injection of USCs six times every week | Did not markedly reduce fasting glucose levels Dong et al. (2016) | ||
| Mice | Single injection of USCs into a sponge | Had no significant effect on blood glucose Ouyang et al. (2014) | ||
| Digestive system diseases | Hepatocyte transplantation | Chronic liver fibrosis mouse model | Promotion of autophagy, proliferation, colony formation, migration and cell fusion | Enhanced liver recovery efficiency Hu et al. (2020), Hu et al. (2021) |
| Nervous system diseases | Neurogenesis | Mouse brain | Seeding of USCs onto a hydrogel scaffold and transplantation into the rat brain | Survived at the lesion site with a great growth rate, differentiated into neuron-like cells Guan et al. (2014) |
| USCs | Combination of laminin and platelet-derived growth factor-BB | Increased levels of neuronal markers (MAP2, NFM and NeuN) Kim et al. (2018) | ||
| USCs in chemical-only induction protocol | Induction of ISX9, I-BET and RA; improved conversion of USCs into neuronal cells | Increased levels of neuron-specific markers (Tuj1, Map2 and Tau), improvement of electrophysiological properties Liu et al. (2020b) | ||
| Spinal cord injury | Spinal cord injury rat models | Elevated expression levels of nerve growth factors and brain-derived neurotrophic factors | Improved motor function in rats Li and Wu (2017), Chen et al. (2018b) | |
| Ischaemic stroke | Rat models of ischaemic stroke | USC‐Exo injection; increased number of EdU+/Nestin+ cells in the subventricular zone | Attenuated neurological deficits, reduced infarct volume Ling et al. (2020) | |
| Oxygen‐glucose deprivation/reoxygenation-processed NSCs | USC‐Exos; exosomal microRNA‐26a | Exerted neurogenic effects on the suppression of histone deacetylase 6 (HDAC6) Ling et al. (2020) | ||
| Locomotor system diseases | Osteoporosis | Ovariectomized rat models | USC-EVs; mediated by the collagen triple-helix repeat containing 1 (CTHRC1) and osteoprotegerin (OPG) proteins | Increased bone mass, effective for the treatment of osteoporosis Chen et al. (2019) |
| Treatment of USC-EVs to promote osteoblastic bone formation | High levels of osteoblast formation-related mRNAs (osteocalcin, Alp, and Runx2) Chen et al. (2019) | |||
| Muscle regeneration | Mice | USCs promote skeletal muscle regeneration | Specific skeletal muscle lineage cell transcripts and protein markers such as myf5, myoD and myosin Chen et al. (2017) | |
| USCs | Combination of USCs and growth factors; hyaluronic-heparin hydrogel scaffold | Increased muscular cell survival rate Liu et al. (2020a) | ||
| Mice with hindlimb suffering due to ischaemia | Transplantation of USC-EVs; angiogenesis | HMEC-1 and C2C12 cell proliferation, muscle regeneration Zhu et al. (2018) | ||
| Cutaneous regeneration and wound healing | Rabbit full-thickness skin defect models | Uses of biocompatible polycaprolactone/gelatine nanofibrous membrane scaffolds | Improved wound contraction, skin appendage regeneration, reepithelialization and neovascularization Fu et al. (2014) | |
| Human umbilical vein endothelial cells (HUVECs) | Significantly enhanced the proliferation, motility and tube formation ability of HUVECs Fu et al. (2014) | |||
| Endothelial cells, full-thickness excisional wounds | Paracrine effects | Improved the proliferation of endothelial cells, promoted fibroblast differentiation, increased the levels of vWF, collagen and fibronectin Zhang et al. (2018) | ||
| Rat full-thickness skin wound models | Proliferation and survival of EAhy926 cells | Accelerated collagen deposition and angiogenesis Cao et al. (2019) | ||
| Seeding of USCs onto a small SIS scaffold in preconditioned hypoxia | Increased the secretion of VEGF, collagen and elastic fibre s Zhang et al. (2020c) | |||
| Streptozotocin-induced diabetic mice | High expression of DMBT1 | Sped up revascularization and collagen deposition Chen et al. (2018a) | ||
| Periodontal tissue engineering | Human periodontal ligament stem cells (PDLSCs) | Noncontact coculture of USCs; improved proliferation and osteoblastic/cementoblastic differentiation of PDLSCs | Increased the density of collagen layers, the levels of the cementogenic protein and ALP activity Yang et al. (2020) | |
| ECM derived from USCs | Enhanced proliferation, osteogenic differentiation potential, and angiogenesis Xiong et al. (2019b) | |||
| Erectile dysfunction | Bilateral cavernous nerve injury (CNI) rat models | Injection of USCs; lower rate of cell apoptosis | Markedly increased the ICP level and the ICP/MAP ratio, increased the ratio of smooth muscle to collagen in the corpus cavernosum Chen et al. (2018c) | |
| USCs modified with pigment epithelium-derived factor (PEDF); antiapoptosis | Exerted protective effects on nerves and ECs in subjects with erectile function Yang et al. (2016) | |||
| Male rat models of streptozotocin injection | Treatment with USC-EVs | Increased endothelial expression and the smooth muscle content, increased the ICP level and the ICP/MAP ratio Ouyang et al. (2019) | ||
| DED rats | USC-EVs; treatment | Increased endothelial expression and the smooth muscle content, increased the ICP level and the ICP/MAP ratio Zhou et al. (2019) | ||