Fig. 1

Overview of iPSC engineering steps for personalized medicine. Step 1: Production of therapeutic iPSCs (three approaches). Approach 1. Production of in-hospital iPSCs. Patient biopsy collected from skin, blood, liver, hair follicles, or urine is reprogrammed by reprogramming factors integrated with viral and non-viral vectors for the production of iPSCs. In-hospital iPSCs are then expanded for further use. Approach 2. Production of commercialized iPSCs. Patient biopsy is collected from the hospital and sent to a company for commercialization. Fully automated processes are used for commercialized iPSC production, followed by a quality assessment. Approach 3. Production of personalized iPSC lines. Patient biopsy is collected from the hospital and sent to a company. Samples are reprogrammed to produce commercialized iPSCs. The commercialized iPSCs are further expanded using bioreactor systems. Purification stages should be performed before the establishment of personalized iPSC lines. Step 2. Engineering of therapeutic iPSCs (four approaches). Approach 1. Engineering iPSCs for paracrine effects. iPSCs release different types of secretomes and regulate cell fate, such as proliferation, angiogenesis, and cell migration. Approach 2. Engineering iPSCs for differentiation. iPSCs are differentiated by electromagnetic factors, mechanical factors, and biomaterial factors. Approach 3. Engineering iPSCs for biomodulation. Different types of engineering techniques are used for biomodulation. iPSC-derived immune cells (T-cells, NK cells) are used for immunomodulation, whereas CRISPR, TALEN, and ZINC fingers are used for genetic modification, which includes disruption, transgene insertion, and gene correction. Approach 4. Engineering iPSCs for pharmaceuticals. Engineering strategies such as organoids, in vitro models, and extracellular vesicles are used for pharmaceuticals. Step 3. Application of engineered iPSCs (three approaches used in various combinations). Approach 1. Tissue regeneration. Engineered iPSCs can either be directly injected or transplanted with scaffolds. Approach 2. Cancer therapy. iPSCs are used for tumor regression through various combinations of engineering strategies. Approach 3. Drug development. Engineered iPSCs are used for drug development and drug screening