Inducing pluripotency in vitro: recent advances and highlights in induced pluripotent stem cells generation and pluripotency reprogramming

Abstract

Induced pluripotent stem cells (iPSCs) are considered patient-specific counterparts of embryonic stem cells as they originate from somatic cells after forced expression of pluripotency reprogramming factors Oct4, Sox2, Klf4 and c-Myc. iPSCs offer unprecedented opportunity for personalized cell therapies in regenerative medicine. In recent years, iPSC technology has undergone substantial improvement to overcome slow and inefficient reprogramming protocols, and to ensure clinical-grade iPSCs and their functional derivatives. Recent developments in iPSC technology include better reprogramming methods employing novel delivery systems such as non-integrating viral and non-viral vectors, and characterization of alternative reprogramming factors. Concurrently, small chemical molecules (inhibitors of specific signalling or epigenetic regulators) have become crucial to iPSC reprogramming; they have the ability to replace putative reprogramming factors and boost reprogramming processes. Moreover, common dietary supplements, such as vitamin C and antioxidants, when introduced into reprogramming media, have been found to improve genomic and epigenomic profiles of iPSCs. In this article, we review the most recent advances in the iPSC field and potent application of iPSCs, in terms of cell therapy and tissue engineering.

New insights into extracellular vesicle biogenesis and function

“…Therefore, induced pluripotency provides a one-of-a-kind approach to generate disease models using patient-specific-derived stem cells, which are especially helpful for the development of new drugs, as well as individualized regenerative therapy approaches. However, this approach requires a significant amount of time to derive stem cells from somatic cells, and the efficiency of this process is extremely low (Takahashi and Yamanaka, 2006;Rony et al, 2015). Moreover, the introduction of stemness genes into somatic cells involves viral infection, making it highly unlikely that the cells could ever be used for therapeutic applications (Rony et al, 2015).…”

“…However, this approach requires a significant amount of time to derive stem cells from somatic cells, and the efficiency of this process is extremely low (Takahashi and Yamanaka, 2006;Rony et al, 2015). Moreover, the introduction of stemness genes into somatic cells involves viral infection, making it highly unlikely that the cells could ever be used for therapeutic applications (Rony et al, 2015). Thus, there is a need for better and more efficient approaches to induce pluripotency.…”

Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts

“…We conducted the reprogramming process by transducing patients' dermal fibroblasts with Sendai virus vectors carrying the OSKM reprogramming factors. Conversely to the use of retroviral or lentiviral vectors, which can produce insertional mutagenic lesions and chromosomal aberration due to their integration into the host genome 29,30 , Sendai virus is transcribed in the cytoplasm, enabling the clearance of the virus as the cells are passaged 31,32 . In fact, we did detect neither virus presence nor expression of the Sendai virus factors by qRT-PCR in the lines studied, thus showing the generation of two "zero-footprint" iPSC-lines.…”

Valproic Acid Enhances iPSC Induction From Human Bone Marrow-Derived Cells Through the Suppression of Reprogramming-Induced Senescence

“…In addition to VPA, many other small molecules have been used to enhance iPSC induction, such as vitamin C (Esteban et al, ), butyrate (Liang et al, ), BIX‐01294 and BayK8644 (Shi et al, ), CHIR99021 (Li et al, ), and lithium (Wang et al, ). Furthermore, maintenance of pluripotency requires specific microenvironments, called stem cell niches, and environmental changes have a great influence on cell function and proliferation (Szablowska‐Gadomska et al, ; Mali and Cheng, ; Rony et al, ). Attempts have been made to improve reprogramming by optimizing pluripotent stem cell culture conditions (Lin et al, ; van der Sanden et al, ; Chen et al, ,).…”