Transgene Delivery to Human Induced Pluripotent Stem Cells Using Nanoparticles

Abstract

Human induced pluripotent stem cells (HiPSCs) and HiPSCs-derived cells have the potential to revolutionize regenerative and precision medicine. Genetically reprograming somatic cells to generate HiPSCs and genetic modification of HiPSCs are considered the key procedures for the study and application of HiPSCs. However, there are significant technical challenges for transgene delivery into somatic cells and HiPSCs since these cells are known to be difficult to transfect. The existing methods, such as viral transduction and chemical transfection, may introduce significant alternations to hiPSC culture which affect the potency, purity, consistency, safety, and functional capacity of HiPSCs. Therefore, generation and genetic modification of HiPSCs through non-viral approaches are necessary and desirable. Nanotechnology has revolutionized fields from astrophysics to biology over the past two decades. Increasingly, nanoparticles have been used in biomedicine as powerful tools for transgene and drug delivery, imaging, diagnostics, and therapeutics. The most successful example is the recent development of SARS-CoV-2 vaccines at warp speed to combat the 2019 coronavirus disease (COVID-19), which brought nanoparticles to the center stage of biomedicine and demonstrated the efficient nanoparticle-mediated transgene delivery into human body. Nanoparticles have the potential to facilitate the transgene delivery into the HiPSCs and offer a simple and robust approach. Nanoparticle-mediated transgene delivery has significant advantages over other methods, such as high efficiency, low cytotoxicity, biodegradability, low cost, directional and distal controllability, efficient in vivo applications, and lack of immune responses. Our recent study using magnetic nanoparticles for transfection of HiPSCs provided an example of the successful applications, supporting the potential roles of nanoparticles in hiPSC biology. This review discusses the principle, applications, and significance of nanoparticles in the transgene delivery to HiPSCs and their successful application in the development of COVID-19 vaccines.

Bioorthogonal non-canonical amino acid tagging to track transplanted human induced pluripotent stem cell-specific proteome

“…Moreover, although both the WT-hiPSCs and L274G-hiPSCs could form teratomas having similar differentiated cell types in vivo, the teratomas derived from L274G-hiPSCs were significantly smaller than those derived from the WT-hiPSCs. It is possible that the introduction of the L274G transgene via lentivirus-based transduction may have affected the OCT4 expression and proliferation rate of the L274G-hiPSCs via introduction of spontaneous mutations [ 46 ]. However, there are several studies that have shown a significant influence of cell line, passage number and site of injection on the teratoma size [ 47 , 48 ].…”

Assessment of laser-synthesized Si nanoparticle effects on myoblast motility, proliferation and differentiation: towards potential tissue engineering applications

“…14 To date, several types of NPs based on polymers, metals and ceramics have been investigated in this respect; most of these studies were thus performed using a variety of stem cells including induced pluripotent stem cells (iPSCs). [15][16][17][18] For instance, Au-NPs functionalized with citrate, chitosan or bronectin, are able to enhance the differentiation of human mesenchymal stem cells (MSCs) and adipose-derived stem cells (ADSCs), respectively, into cardiomyocytes and osteoblasts. 19,20 Ag-NPs can promote osteogenic differentiation of human urine-derived stem cells (USCs) and the proliferation of MSCs, 21 while graphene-based NPs enhance the cardiomyogenic and angiogenic differentiation capacity of MSCs for cardiac tissue regeneration.…”

Special Issue “Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions”

“…This review highlighted the current strategies, future perspectives, and challenges of the NPmediated diagnosis and treatment of thrombosis obstructs, atherosclerosis, hyperlipidemia, hypertension, pulmonary arterial hypertension, and ischemic stroke. Finally, Yamoah et al reviewed recent NP-mediated transgenic gene delivery to human-induced pluripotent stem cells (hiPSCs) [14]. The authors highlighted the advantages of NP-mediated transgene delivery over other methods, including high efficiency, low cytotoxicity, biodegradability, low cost, directional and distal controllability, and efficient in vivo application.…”