Patient-Specific Induced Pluripotency Stem Cells (PSiPS)’
The current clinical trial, ‘Patient-Specific Induced Pluripotency Stem Cells (PSiPS)’ was sponsored by the Royal Institute (Clinicaltrials.gov. n.d). Since Dr. Shinya Yamanaka discovered 4 transcription factors that could reprogram adult cells to pluripotency, successful clinical trials such as the use of PSiPS, have led to the expansion of a range of possibilities for regenerative medicine treatments (Sayed 2016, p. 2166). The rationale for conducting the clinical is based on the findings that pluripotent stem cells can differentiate into a variety of cell types, both in vitro and in vivo. Medical scientists can now carry out drug tests using either embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), the two types of pluripotent stem cells (Picanço-Castro 2014, p. 98). The purpose of this assignment is to describe how the differentiation of pluripotent stem cells is applied in clinical trials, as well as the outcome and the implications of the clinical trial for future regenerative medicine treatments.
Study Description
The clinical trial involved the application of Induced Pluripotency Stem Cells (PSiPS), which are adult cells developed by genetically reprogramming them to a desired state that models an embryonic stem cell. Researchers do this by forcing the cells to express factors and genes that are important in the maintenance of the defining embryonic stem cell properties. The trials conducted in the programming of adult cells, usually somatic cells, into the desired embryonic stem (ES) cells has helped medical researchers to generate patient-specific stem cells, and thus discovered an enormous potential of treating and analyzing degenerative diseases (Picanço-Castro 2014, p. 101).
Study Design
The title given for the study was ‘Patient-Specific Induced Pluripotency Stem Cells’ (PSiPS)’ methodology selected for the clinical trial was observational. The research involved the use of fifteen participants in the Case-only prospective study. The procedure selected for the study is a skin biopsy. The study was scheduled to begin in April 2009 and be complete by January 2010, but the actual completion date was July 2010. Also, no disease was selected for piloting in this trial (Clinicaltrials.gov. n.d).
Ascertaining the possibility of using pluripotent stem cells is the first phase in the clinical trial process, phase zero. The phase had already been completed before the commencement of the actual clinical trials. The current clinical trial project involved the induction of pluripotent stem cells of skin biopsies of patients obtained from cell cultures. The next step was the development of iPS cells for modeling drugs and disease discovery, and for future basic research (Picanço-Castro 2014, p. 98).
In phase zero, the research team conducted all the necessary processes to determine the safety of using the iPS cells as a possible treatment intervention. The safety of using pluripotent stem cells in therapeutic interventions is based on adherence to safe differentiation protocols. The researchers were required to ensure that the differentiation of the cells was well controlled to avoid teratoma formations (Picanço-Castro 2014, p. 99), tumor-like formations with tissues associated with all the three germ layers (Kammili et al 2010, p.142).
Derivation of iPS cells
An applicable process in phase one, the iPS cells’ derivation cells in a clinical trial typically derived by the use of viral vectors, for example, retroviruses, in the transfection of certain genes associated with stem cells into non-pluripotent cells, preferably adult fibroblasts. Transfected genes are Sox2 and the master transcriptional regulators Oct-3/4 (Pouf51), although some other genes, such as Klf4 and c-Myc may be used to improve the efficiency of the induction. In the current clinical trial, fibroblasts were separated from the skin biopsy of a patient. The cells were then transfected with four Yamanaka factors, including human Sox2, Oct4, c-Myc, and Klf4 after 3-4 weeks. Next, the researchers isolated the transfected cells through morphological selection (Clinicaltrials.gov. n.d.).
Clinical outcomes
The findings of the clinical trial published in 2010 paper in the journal known as Stem Cells indicated that the tumorigenic risk posed by the application of iPS cells raises more serious concerns compared to ESC. The findings supported the notion that iPS is less safe to apply at that moment and should be shelved until other methodologies proved it more effective Picanço-Castro 2014, p. 107).
Implications of the Clinical Trial for Future Perspectives
One of the challenges the clinical trial faces in future regenerative medicine treatments may be associated with epigenetic and genetic variability. However, ES cells are promising models for disease treatment mainly because of three key factors. The outcomes in the clinical trial correspond with three key factors that support the effectiveness in the use of ES cells in therapeutic interventions. The factors include the huge capacity of ES cells for scale-up making it possible to create allogeneic cell banks; the ability to differentiate almost any cell type applicable in therapeutic interventions; and many researchers have used many of them in several clinical trials (McKay 2020).
Many safety-related questions require answers concerning the use of induced pluripotent stem cells (iPSCs) in disease treatment and drug development. , the proposed intervention great advancements have been achieved to prove scientifically that iPSCs can be effective in the development of drug models against certain diseases. Another implication of the clinical trial is that the findings could increase understanding of human embryonic development, which is an invaluable resource in modeling disease pathogenesis and treatment.