Potential of Induced Pluripotent Stem Cells for Use in Gene Therapy: History, Molecular Bases, and Medical Perspectives

Abstract

Induced pluripotent stem cells (iPSCs) are defined as reprogrammed somatic cells exhibiting embryonic stem cell characteristics. Since their discovery in 2006, efforts have been made to utilize iPSCs in clinical settings. One of the promising fields of medicine, in which genetically patient-specific stem cells may prove themselves useful, is gene therapy. iPSCs technology holds potential in both creating models of genetic diseases and delivering therapeutic agents into the organism via auto-transplants, which reduces the risk of rejection compared to allotransplants. However, in order to safely administer genetically corrected stem cells into patients’ tissues, efforts must be made to establish stably pluripotent stem cells and reduce the risk of insertional tumorigenesis. In order to achieve this, optimal reprogramming factors and vectors must be considered. Therefore, in this review, the molecular bases of reprogramming safe iPSCs for clinical applications and recent attempts to translate iPSCs technology into the clinical setting are discussed.

Osteogenesis Imperfecta: Current and Prospective Therapies

“…iPSCs have been used for the first time in a clinical trial (first phase) in 2014 in Japan for retinitis pigmentosa treatment [58]. Additionally, iPSCs generated in a patient-specific manner have therapeutic potential in autologous transplants for treatment of retinitis pigmentosa, haemophilia A, severe combined immunodeficiency (SCID), myotonic dystrophy and Sandhoff disease [59]. Therefore, personalized iPSCs constitute an invaluable cell type for use in replacement therapy.…”

“…The ability of blood cells reprogramming is a novel perspective for clinical practice, as blood collection is a standard test. Additionally, HLA matching has a crucial role in the limitation of alloimmune responses [59].…”

Multilineage-Differentiating Stress-Enduring Cells (Muse Cells): An Easily Accessible, Pluripotent Stem Cell Niche with Unique and Powerful Properties for Multiple Regenerative Medicine Applications

“…In the last decade, particular attention has been given to the study of different types of cells and to their application to favor and promote regenerative processes and for the cell-based treatment of many diseases [ 1 , 2 ]. In particular, great interest in research has been aroused by stem cells; their self-renewal capacity and their ability to differentiate into mature adult cells make them promising for human tissue regeneration [ 3 , 4 ]. Indeed, stem cells and their differentiated derivates are increasingly used in a number of cell-based therapies and are being studied worldwide, with the hope of healing the cell loss condition correlated to various diseases [ 5 ].…”

“…They are widely used to obtain stem cells with regenerative potential [ 12 ]. Unlike human ESCs, iPSCs raise no ethical concern regarding the onset of human personhood [ 3 , 5 ]. Unfortunately, with the use of these cells, there is the important risk of tumor formation, risk correlates with both pluripotency and self-renewal, and this has emerged as a critical factor in determining the pluripotent capacities of both ESCs and iPSCs [ 11 ].…”

A Comprehensive Review of the Therapeutic Value of Urine-Derived Stem Cells

“…Thus far, USC-iPSCs have been reported to rapidly proliferate and efficiently differentiate into many cell types with higher yields and less immunological rejection, mainly in endocrine systems ( Guo et al, 2017a ; Guo et al, 2017b ) and digestive systems ( Niemietz et al, 2016 ). In addition, USC-iPSCs can potentially be used to establish disease models based on their ability to provide an unlimited source of cells with the same genes as diseased cells ( Fus-Kujawa et al, 2021 ). However, iPSCs are characterized by genetic instability and self-renewal ability, especially in regards to undifferentiated pluripotent stem cells forming tumours in the body, which is particularly worrying.…”