Recently, a research team from Osaka University in Japan used human derived induced pluripotent stem cells (iPSCs) to selectively differentiate corneal epithelial cell sheets for the first time in the world, repairing the cornea of patients with corneal limbal stem cell deficiency and visual impairment. They plan to launch a larger clinical trial this year to evaluate the efficacy. The relevant research was recently published in the international academic journal The Lancet. At the same time, Deng Hongkui, a professor of Peking University, published a research paper in the international academic journal Cell, and reported for the first time the clinical research results of islet cell transplantation prepared by chemical reprogramming iPSC, which successfully cured type 1 diabetes, indicating the safety and functionality of clinical application of iPSC technology. In recent years, the basic and clinical research on iPSCs has developed rapidly, demonstrating enormous potential for applications in disease in vitro model construction, drug screening, cell therapy, and other fields Zhao Mingming, a professor at the School of Basic Medicine of Chongqing Medical University and the head of the iPSC Research Center at the Affiliated Children's Hospital, said in an interview with Science and Technology Daily that iPSC technology research will promote a new leap in regenerative medicine. 'Omnipotent' cells are widely used. Embryonic stem cells (ESCs) are a type of pluripotent stem cell and the best material for regenerative medicine applications. However, serious harm or even killing of embryos is difficult to avoid when obtaining human ESC, so the acquisition of human ESC is subject to both ethical and legal constraints. In 2006, Japanese scientist Shinya Yamanaka successfully converted mouse skin fibroblasts into pluripotent stem cells similar to ESCs using four reprogramming factors, effectively avoiding the ethical issues faced by ESCs. He was also awarded the 2012 Nobel Prize in Physiology or Medicine for this. In 2009, Chinese scientists Zhou Qi and others cloned living and reproductive mice using iPSCs, confirming for the first time internationally that iPSCs, like ESC, possess pluripotency. Zhao Mingming told reporters that the versatility of iPSCs is mainly reflected in two directions: firstly, iPSCs are derived from adult cells and can retain the genetic information of existing adult cells, which can be used as a cell source for constructing in vitro models of diseases. Secondly, iPSCs have high differentiation potential, theoretically capable of differentiating into all specific cell types in the human body, with low immune rejection reactions, and can provide an ideal cell source for regenerative medicine. Li Fanghuan, Deputy Chief Physician of Ophthalmology at Peking University People's Hospital and Leader of the Corneal Disease Professional Group, introduced that the latest research results of the Osaka University research team and Deng Hongkui's team are the specific applications of iPSC in the field of regenerative medicine. The two research teams reprogrammed the extracted human somatic cells into iPSC, and then transformed them into corneal epithelial cell grafts and islet cells to transplant them into patients, so as to achieve the treatment of limbal stem cell deficiency and diabetes. In addition, the accessibility and genetic stability of iPSCs make them equally outstanding in the construction of in vitro disease models and drug screening. Li Fanghuan said that the pathogenesis of many diseases is complex. Researchers can use iPSC technology to cultivate specific cells in vitro, which can provide a more intuitive and accurate understanding of the pathological mechanisms of diseases, and thus carry out personalized drug screening and precision medical strategy development. For example, in the field of neuroscience, researchers have induced iPSCs derived from humans into motor neurons and dopaminergic neurons, respectively, and established models of amyotrophic lateral sclerosis and Parkinson's disease, opening up new directions for the study of related disease mechanisms. Research achievements are constantly emerging. Since the birth of iPSC in 2006, the scientific community has conducted increasingly in-depth research on it, and related studies can be described as diverse. "Pan Shaohui, a researcher at the Stem Cell Research Institute of Wenzhou Medical University, said that China, Japan, and the United States are the main forces in iPSC research, and have achieved many results in the study of reprogramming mechanisms, as well as cell therapies in the fields of neural lineage, blood system, and so on. Pan Shaohui introduced that as the country of origin of iPSC research, Japan has conducted multiple clinical studies using iPSCs for disease treatment. In 2014, a Japanese research team completed the world's first iPSC treatment for age-related macular degeneration, pioneering clinical research on iPSC; In 2018, the iPSC Research Institute at Kyoto University conducted clinical research on the treatment of aplastic anemia using iPSC derived platelets from patient sources; So far, the Osaka University research team has completed multiple cases of iPSC myocardial membrane transplantation surgery, providing rich clinical trial evidence for the treatment of severe heart failure. The reporter learned that research in related fields in China began around 2012. Although it started relatively late, its development has been rapid, and many teams have conducted a series of basic research and clinical application studies. Zhao Mingming said that many research teams in China, based on clinical needs, have made fruitful achievements in iPSC induced differentiation research and clinical research on the application of iPSC in the treatment of diabetes, chronic end-stage heart failure and rare diseases. He gave an example that Deng Hongkui's team was the first to develop chemical reprogramming technology, which uses chemical small molecules to make iPSCs. It has the advantages of high controllability and easy operation, effectively solving the problems of random gene integration and oncogenes that may be caused by traditional cell reprogramming methods. In order to further explore the potential of iPSC technology in the study of mechanisms of rare diseases in children, tissue and organ regeneration, personalized medicine, and other fields, the iPSC Research Center of Chongqing Medical University Affiliated Children's Hospital was established in August 2024, dedicated to establishing a rare disease iPSC repository and exploring the construction of in vitro disease models. Zhao Mingming said, "Relevant research is expected to bring new hope for the treatment of rare disease patients." The clinical application path is blocked and long. "Currently, almost all iPSC research is in the clinical phase I and II experimental stages, and there is still a long way to go before clinical translation and application." He Xiangyu, director of the ophthalmology department of Jiangbei Branch of Southwest Hospital of Army Medical University, believes that in order to achieve the clinical application of iPSC, it is urgent to break through the development difficulties of immune rejection, tumor risk, and low differentiation efficiency induced by iPSC technology. He Xiangyu introduced that the latest research direction of the ophthalmology team at Southwest Hospital of Army Medical University is to use patient derived iPSCs to treat hereditary retinal degeneration diseases. The research team found that if patients have genetic defects, the iPSCs prepared from their cells and the induced therapeutic cells also have corresponding genetic defects, which leads to immune rejection of iPSCs after implantation in the patient's body. It is reported that Japan has discovered two genetic mutations in iPSC and differentiated retinal cells after completing the world's first retinal disease iPSC therapy transplantation surgery, which poses a certain risk of tumorigenesis. The research team subsequently announced the discontinuation of this clinical trial. The tumorigenicity of iPSCs has attracted widespread attention from scientists. He Xiangyu explained that on the one hand, the multipotent genes used to induce somatic cell reprogramming into iPSCs have been proven to be oncogenes involved in tumor formation; On the other hand, gene mutations such as karyotype abnormalities can also occur during the in vitro cultivation of iPSCs. Although chemical reprogramming technology can effectively prevent cell carcinogenesis, it also has the drawbacks of long induction time and low efficiency. At present, the reprogramming mechanism of iPSC is still unclear and requires further research Zhao Mingming suggested that researchers from various fields and relevant technology-based enterprises should form a joint force to develop more efficient induction methods to improve the differentiation efficiency of iPSCs, and establish standardized iPSC quality inspection standards to accelerate the clinical application and industrial development of iPSCs. (New Society)