From: Engineering considerations of iPSC-based personalized medicine
Applications | Engineering Strategy | Cell Types | Targets | Features | Outcomes | References |
---|---|---|---|---|---|---|
Tissue Regeneration | Paracrine Effects | Cardiac Cells | Cardiac tissue | Increased angiogenic potential, secretion proangiogenic and proinflammatory cytokines | Recovery from human acute myocardial infarction | [120] |
Cardiac Cells | Cardiac tissue | Up to 80% of cardiomyocyte differentiation was increased by Wnt treatment | Cardiomyocyte differentiation through paracrine factors | [121] | ||
Cardiac Cells | Cardiac tissue | Enhancement of promigratory, proangiogenic, and antiapoptotic | Effective recovery of damaged myocardium | [112] | ||
Cardiac Cells | Cardiac tissue | Secretome suppressed apoptotic cardiomyocytes > 70% locally | Heart muscle extracellular signals for cell-free treatment | [122] | ||
Neurons and glial cells | Neuron tissue | The Ang 1–7/Mas receptor inhibited aging and decreased neurodegenerative susceptibility | Therapeutic strategies for Parkinson’s disease | [123] | ||
Neurons and glial cells | Neuron tissue | Iinduced neurotrophic and neuroprotective effects and decreased the number of necrotic and apoptotic cells | encourage the development and expansion of neurites | [124] | ||
Neurons cells | Neuron tissue | Resource for transcriptomics on corticogenesis in 5 situations | Neurons were variable, and more developed | [125] | ||
Renal cells | Kidney tissue | Microbioreactor array–based multicellular differentiation | Identification of renal cells | [126] | ||
Murine bone cells | Bone tissue | Expression of the osteogenic genes via paracrine mechanisms | BMP-2, BMP-4, and BMP-6 gene expression is increased | [91] | ||
Hepatic cells | Liver tissue | The Transwell system of HE-iPSCs was separately co-cultured with MSCs and/or HUVECs | Regulate the differentiation of human hepatocytes | [127] | ||
Differentiation | Vascular smooth muscle cell | Vascular grafts tissue | Incorporating biodegradable scaffolds, progressive pulsatile stretching | Non-immunogenic, cellularized vascular grafts | [128] | |
Vascular smooth muscle cell | Vascular tissue | PGA scaffolds express mature VSMC marker | Formation of autologous human vascular tissues | [129] | ||
Cardiac Cells | Cardiac tissue | Human endothelial cell patches and cell-free patches | Electrical coupling improved left ventricular function by 31% | [130] | ||
Cardiac and endothelial cells | Cardiac tissue | A cardiac muscle patch was created by 3D printing a scaffold with seeding cardiomyocytes and smooth muscle cells | Cell engraftment was 24.5% at week 1 and 11.2% at week 4 than cell-free scaffolds | [131] | ||
Lymphoblastoid cells | Cardiac tissue | Modifiable DNA methylation, chromatin accessibility, and gene expression levels | Identify the impact of chromatin accessibility specific to different cell types | [132] | ||
Mesodermal cells | Muscle tissue | Dystrophic mice's hearts and skeletal muscles can successfully engraft with human MiPSC | Cocktails of miRNA encourage myogenesis | [133] | ||
Endothelial cells | Lung tissue | Enhancing endothelial colony forming cells-built lung scaffolds with 8CPT-2Me-cAMP | Improved endothelial functionality | [134] | ||
hiPSC lines | Endoderm | Endoderm differentiation using a single-cell RNA-based population | Used for genetic background variability assessment | [135] | ||
iPSC-derived MSCs | Bone tissue | Better osseous consolidation was seen with HFF-iMSC + CPG transplantation compared with CPG alone | Express of osteopontin and bone morphogenic proteins | [136] | ||
Endothelial cells | Endothelial tissue | Medium supplemented VEGF is differentiated into endothelial cells | Functional cues to promote cell attachment, survival, and differentiation | [137] | ||
hiPSCs | Inner ear hair cells | Using CRISPR/Cas9, the MYO15A mutation was genetically fixed, saving the morphology and function | Gene mutation-based deafness can be functionally restored | [138] | ||
Biomodulation | hiPSCs | Footprint-free MSCs | Wnt3a, Activin A, and BMP4 had synergistic effects on MSC after just 4Â days of therapy and microbead encapsulation | Create osteogenesis, chondrogenesis, and adipogenesis lineages without teratoma development in vivo | [139] | |
MSCs | Bone tissue | Scaffolds: GO was cross-linked with N-hydroxy succinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride | Less than 0.5% GO was biocompatible and encouraged osteogenesis and proliferation | [140] | ||
MSCs | Cardiac tissue | Direct injection of saline 2 × 108 hESC-CMs or 2 × 108 hiPSC-MSCs into the myocardium | No proarrhythmia or tumor formation and improvement of cardiac function | [141] | ||
Pharmaceuticals | iPSC-derived EVs | Neuron tissue | Electroacupuncture and iPSC-derived extracellular vesicles on mice with ischemic stroke | Treatment for ischemic stroke and damaged tissues | [142] | |
iPSC-derived EVs | Neuron tissue | Motor neurons load mRNAs into EVs to control specific processes | Differentiated into motor neurons | [115] | ||
Cardiac Cells | Cardiac tissue | Post-infarction remodeling, extracellular vesicles released by ISX-9-induced CPCs | Increased angiogenesis, cardiomyocyte proliferation, and used in heart infarction treatment | [143] | ||
Cancer Therapy | Paracrine Effects | Endothelial cells | Breast cancer | Organotypic microfluidic model of human vasculature upregulated secreted factors during cancer cell extravasation | Increased levels of IL-6, IL-8, and MMP-3 and assessment of therapeutic drugs in cancer metastasis | [144] |
iPSC | Cell-derived tumors | Hypoxia-inducible factor-1-alpha-regulated matrix metalloproteinases operate as a mediator downstream of mTORC1 | Development of stem cell-derived tumors | [145] | ||
iPSC | Osteosarcoma | The tumorigenic potential is repressed by suppression of SFRP2, FOXM1, or CYR61 | A potential treatment approach is to suppress SFRP2 | [146] | ||
Differentiation | Antigen-specific T cells | Xenograft cancer models | Differentiating CD8ab T cells into antigen-specific TCR | impede the growth of tumors in xenograft cancer models | [147] | |
Mouse iPSCs | Tumor vasculature | The recruitment of host endothelium vessels into the tumor is aided by cancer stem cells | Investigate the tumor vasculature and create fresh approaches to targeting | [148] | ||
Cardiac Cells | Breast Cancer | Without causing cardiomyocyte death, clinically relevant doses of trastuzumab reduced the iPSC-CMs' ability to contract and handle calcium | Mechanism behind the emergence of heart dysfunction is changes in cellular metabolic pathways | [149] | ||
Biomodulation | NK cells | Ovarian cancer xenograft mode | Comparing T-CAR-expressing iPSC-derived NK cells and non-CAR-expressing cells, CAR exhibit antitumor efficacy | "Off-the-shelf" targeted lymphocytes for immunotherapy against cancer | [18] | |
NK cells | Tumor lysis | Enhance cytokines, cytotoxicity against solid and hematologic malignancies, and attracted T cells and anti-PD-1 antibodies | Encouraging the infiltration of T cells to enhance checkpoint inhibitor treatments | [107] | ||
NK cells | NK cells mediated tumor | Through the expression of CD16A, CD64/16A, and the altered NK cells, tumor cell death was mediated | IgG Fc chimeric proteins and therapeutic mAbs with switchable targeting components | [150] | ||
Macrophages | Removal cancer cells | CAR expression improves tumor cell phagocytosis, polarizes macrophages, and secretes cytokines | Utilized to eliminate cancer cells | [113] | ||
Macrophages | Disease models | iPSC line SFCi55-ZsGreen is used to produce terminally differentiated macrophages | Used to track disease model progression in vivo | [151] | ||
MSCs | in vitro and in vivo Anti-tumor effects | Through apoptotic signaling pathways, TRAIL-iMSCs reduced tumor growth in xenografts of the A549 or MCF-7 | High homogeneity therapeutic gene-targeted MSCs for cancer treatment | [152] | ||
MSCs | Facial Tumor | iMSCs were differentiated by transforming growth factor beta/activin signaling pathway inhibition | Immunomodulatory and anti-inflammatory | [153] | ||
Cytotoxic T lymphocytes | Cervical cancer | Revealed strong cytotoxicity against cervical cancer after differentiating into HPV16-specific regenerated CTLs | Tumors overwhelm result on epithelial cancers | [154] | ||
Drug Development | Paracrine Effects | Cardiac Cells | Cardiovascular disease | H9C2 cells are protected against stress-induced senescence by blocking the p53-p21 and p16-pRb pathways | Therapeutic approach for cardiovascular disease | [155] |
Differentiation | iPSCs and ESCs | Blood cells | Mature blood cells are formed in part by chromatin state, DNA methylation, and gene expression | the best way to choose iPSCs for clinical purposes | [156] | |
iPSCs | Hepatocytes and adipocytes | Transcriptomic and metabolomic effects of the 1p13 rs12740374 variation on cardiometabolic markers | Tools for GWAS variant validation | [157] | ||
iPSCs | Hematopoietic cells | DNA methylation and gene expression patterns associated with leukemia | Examining the clonal characteristics of human AML | [158] | ||
iPSCs | Microglia | Exposure to certain stimuli and co-culture with astrocytes to induce microglial differentiation | Similar functional traits of isolated Microglia from the brain | [159] | ||
Biomodulation | iPSCs | Hematopoietic cells | Myeloid malignancy is caused by the chromosome 7q loss and the splicing factor SRSF2 P95L mutation | Drug discovery and testing are done with hematopoietic cells | [160] | |
iPSC-derived MSCs | Immunomodulatory effects | T cell responses as an action of soluble factors and inhibiting the cleavage of caspases | Immunomodulatory effects on T cell responses | [161] | ||
iPSCs | Strong immunomodulatory | Decreased c-Myc expression and downregulation of the DNA replication pathway | Low oncogenicity and strong immunomodulatory, good potential for therapeutic use | [162] | ||
Ligament and gingival Cells | iPSC-MSC | To raise the number of Treg cells while decreasing the number of Th1/Th2/Th17 populations and T-cell effectors | Clinical use in therapeutic applications and potent immunosuppressive properties | [163] | ||
MSCs | Myocardial infarction | Intravenous infusion of 5 × 105 or 1 × 106 hiPSC-CMs | enhance cardiac function in myocardial infarction | [164] | ||
Pharmaceuticals | Liver cells | Liver diseases | Apolipoprotein B synthesis is inhibited by cardiac glycosides | Treatments for inborn errors of hepatic metabolism | [114] | |
Liver cells | Liver fibrosis | qHSC-like cells converted into activated HSCs in culture | Investigate the therapeutic compounds connected to HSCs' | [165] | ||
Liver cells | Liver injury | Identified key drug transporters and metabolizing enzymes | Utilized in tests for toxicity, excretion, and metabolism | [166] | ||
Liver cells | Hepatotoxicity assessment | Using confocal and 3D image analysis, several spheroid phenotypes compared multi-parametrically | Differences between the two cell types' pharmacological effects | [167] | ||
Liver and cardiac cell | Drug efficacy, and toxicity assessment | By the cytochrome P450 enzyme in the liver MPS, cisapride is metabolically converted to nonarrhythmogenic norcisapride | Screening of the liver and heart for medication effectiveness, and toxicity | [168] | ||
Neuron cells | Neurological mtDNA Disorders | Avanafil drug partially corrects the calcium deficiency in patient NPCs and differentiated neurons | Model for testing drugs for mtDNA diseases | [169] | ||
Neuron cells | Alzheimer’s Disease | Topiramate is an anti-Ab cocktail comprised of a combination of 27 Ab-lowering screen hits, prioritized hits, and 6 leading compounds | Beneficial in the development of drugs for Alzheimer's disease | [170] | ||
Cardiac cells | Drug-induced clinical trials | Values of field potential duration prolongation and clinically concentrations were associated | Demonstrate the feasibility of in vitro preclinical studies | [171] | ||
Cardiac cells | Cardiac disease | Isoproterenol and verapamil 3D-printed an asymmetric, cantilever-based tissue scaffold | Drug discovery via high-throughput screening | [172] | ||
Macrophages | Modeling of Tissue Resident Macrophage | Growth factors and particular organ specific cues can help macrophages differentiate | iMacs with pro-inflammatory characteristics, mimicking the disease phenotype | [173] | ||
Cardiac cells | 3D-iPSC cardiomyocyte tissues for drug development | iPSC-CM tissues offer blood capillary-like networks and synchronous beating ratios | Compared to 2D-iPSC-CM cells, 3D-iPSC-CM tissues showed hazardous reactions | [174] |