Induced pluripotent stem cells (iPSCs) are the cells that are reprogrammed from somatic cells using different transcription factors, eliminating ethical considerations associated with scientific work based on embryonic stem cells. Recent progress in iPSCs research has paved the way for patients to reap the benefits of regenerative medicine and therapies. iPSC-based stem cell therapy has become a very promising and advanced scientific research topic.
iPSCs are generated by reprogramming somatic cells and possess unique properties of self-renewal and differentiation to many types of cell lineage. They were firstly generated from mouse fibroblasts by the introduction of four transcription factors (Oct4, Sox-2, c-Myc, and Klf-4) through genetic reprogramming. With the guide of different protocols, iPSCs can differentiate into any type of cells theoretically, including neural cells, cardiomyocytes, chondrocytes, retinal pigment epithelial cells, pancreatic islet cells, and hepatocytes.
Fig.1 Schematic overview of iPSC derivation from a patient or healthy subject. (Doss, 2019)
The induction of pluripotency in somatic cells is widely considered as a breakthrough in regenerative medicine and individualized stem cell-based therapies. iPSCs have become attractive candidates for cell therapy-based regenerative medicine, moreover, patient-derived iPSCs can be applied in multiple critical in vitro studies, such as in vitro disease modeling, toxicity screens, drug development, drug delivery and so on.
Fig.2 Generation and applications of iPSCs. (Moradi, 2019)
iPSCs are of great value in studying the molecular mechanism of many diseases. They have been widely employed in various diseases for disease modeling and gene therapy. iPSCs-derived disease models show significant advantages compared with many animal models, such as rats, mice, monkeys, dogs, and primates. They can fully mimic the human cell microenvironment and overcome the challenge in genetic differences between different species. Up to now, iPSCs have played important roles in revealing the molecular networks that drive the different aspects related to diseases' pathogenesis, including neurogenerative diseases, cardiovascular diseases, chromosomal diseases, cancers, etc.
iPSCs-based cell therapy has proven to be very powerful and instrumental in biomedical research and personalized regenerative medicine. They have shown a promising prospect in a wide range of diseases, such as neurodegenerative diseases of the central nervous system (CNS), heart infarction, diabetes mellitus, liver diseases, lung diseases, and kidney diseases. The first step of iPSCs therapy is that iPSCs are differentiated into the desired cell types of interest, and then, the resulting specialized tissue-specific cells are transplanted as cell suspensions or more complex tissue constructs into patients. In 2014 in Japan, the first clinical trial of autologous iPSC-derived retinal pigment epithelial cells was launched to treat age-related macular generation (AMD). These ongoing clinical trials raise tremendous hopes that the iPSC technology will bear fruit in the years.
iPSCs have presented an unprecedented opportunity in drug delivery research. By creating a novel human blood-brain barrier (BBB) microphysiologocal system consisting of bilayer coculture of human astrocytes, and endothelial cells, derived from iPSCs, scientists can significantly facilitate the research of neuro-pharmaceutical drug delivery, screening, and transport.
3D bioprinting of iPSCs or iPSC derived cells to create multiscale tissue architectures, has evolved as a tool to create regenerative medicine and patient-specific treatment. This technology enables to recapitulate microarchitecture of specific tissues and promotes the tissue engineering purpose of replacing or regenerating damaged and diseased tissues. The main obstacle in bioprinting undifferentiated iPSC is their sensitivity to mechanical forces during the printing process, so the bioprinting parameters should be carefully optimized before bioprinting.
Organoids are in vitro cultured three-dimensional cell cultures that recapitulate key features of in vivo organs. Because they have the genetic and physiological similarity required for the modeling of human diseases, organoids are useful in future disease modeling and drug screening applications for assessing efficacy and safety. There are a series of organoids have been developed, including intestine, liver, kidney, pancreas and brain.
iPSCs and iPSC-derivatives (growth factors, cytokines, differentiated tissue cells/progenitors, etc.) may serve as a source of autologous bioactive agents that could be utilized for future clinical translation to treat various diseases. It has been reported that exosomes from iPSC-derivatives can be applied to enable an autologous therapy by simulating endogenous repair, providing higher therapeutic specificity, quality control, ease of production, and safety than stem cell transplantation.
Although there are many unaddressed challenges in iPSC technology, such as the low efficiency of their reprogramming and differentiation, iPSCs are entirely changing the traditional therapy in biomedical research. With a decade of experience in stem cell therapy development, Creative Biolabs provides high-quality iPSC reprogramming, iPSC differentiation, iPSC characterization services to our customers all over the world. Please feel free to contact us for a discussion with our scientists.
References
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