The Application of Induced Pluripotent Stem Cells in Stem Cell Research and Ther

Posted by Chelsea Clark on December 31st, 2020

Induced pluripotent stem cells (iPSC) can self-renew indefinitely in culture and differentiate into all specialized cell types, including gametes. iPSC does not exist naturally but is produced from somatic cells ("induced" or "reprogrammed") in culture through ectopic co-expression of determined pluripotency factors. Since they can be produced from any healthy person or patient, iPSCs are regarded as a valuable resource for regenerative medicine to replace diseased or damaged tissues. In addition, reprogramming technology provides powerful tools for studying cell fate determination mechanisms and simulating human diseases, thereby greatly enhancing the possibility of discovering new drugs in the form of screening and treating life-threatening diseases through cell therapies based on strategies.

Human iPSC is in many diseases that cannot be cured or effectively treated, such as neurodegenerative diseases of the central nervous system, heart disease, diabetes, and liver, lung, and kidney. Given that iPSC can be produced in a patient-specific way, it can be used for autologous transplantation, thereby avoiding the complications of host immune system rejection. Various methods have been used to induce the pluripotency of somatic cells, which can be classified as integrated methods, in which exogenous DNA sequences encoding reprogramming factors are inserted into the genome of the starting cell, and non-integrated methods, which does not require permanent genetic modification. Although the iPSC generated by the integrated method can be effectively used for basic research, the discovery of new drugs, screening of toxins, and in vitro disease simulation, the non-integrated method has significant advantages and can potentially produce “safe” iPSCs, thereby gaining success. Epidemic minimizes disease-causing mutations and is therefore considered more suitable for cell-based therapy.

Although non-integration methods are the preferred strategy for safe iPSC generation, in certain specific situations (for example, genetic methods to correct genetic diseases), it is possible to use integrative vectors or viruses. It is worth noting that, out of consideration of the safety of the application of genetically modified iPSCs in humans, regulatory agencies have always had strict inspection policies for the use of genetically modified cells for patient treatment. The recent approval of several genetically modified cell products has opened up new areas for gene therapy and has led to many clinical trials being carried out worldwide to study various gene therapies using different gene-editing tools (such as TALEN and CRISPR/Cas9 systems).

It is worth mentioning that one of the key challenges in producing genetically modified iPSCs for cell therapy is the production of clinical-grade viral vectors. The production of such carriers under GMP conditions requires special equipment, as well as experienced facilities and skilled operators. Therefore, the safety of clinical-grade carriers must be confirmed to provide the highest level of reliability and patient safety.

iPSC opens up new avenues for stem cell research and brings unique opportunities for the pharmaceutical industry and clinical practice. However, as in many other fields, reprogramming technology has its own ethical and social issues, and all these issues must be carefully considered. Laws and standards must be formulated to ensure the ethical integrity of iPSC production/application and at the same time eliminate unnecessary obstacles in iPSC research and treatment methods.

In short, informed consent must be obtained from both the cell donor and recipient. Since the donated cells contain private information in the form of DNA, the privacy of the donor and patient must be protected. At the beginning of cell donation, donors should be made aware of how long they can control their cells. All steps from the isolation of donor somatic cells to iPSC production and its application to iPSC-based cell therapy for iPSC derivative transplantation must be performed under GMP conditions. The safety of the method of deriving or distinguishing iPSC is very important. Especially if the cells have been genetically manipulated, specific quality control tests are required.