Abstract

The year 2006 will be remembered monumentally in science, particularly in the stem cell biology field, for the first instance of generation of induced pluripotent stem cells (iPSCs) from mouse embryonic/adult fibroblasts being reported by Takahashi and Yamanaka. A year later, human iPSCs (hiPSCs) were generated from adult human skin fibroblasts by using quartet of genes, Oct4, Sox2, Klf4, and c-Myc. This revolutionary technology won Yamanaka Nobel Prize in Physiology and Medicine in 2012. Like human embryonic stem cells (hESCs), iPSCs are pluripotent and have the capability for self-renewal. Moreover, complications of immune rejection for therapeutic applications would be greatly eliminated by generating iPSCs from individual patients. This has enabled their use for drug screening/discovery and disease modelling in vitro; and for immunotherapy and regenerative cellular therapies in vivo, paving paths for new therapeutics. Although this breakthrough technology has a huge potential, generation of these unusual cells is still slow, ineffectual, fraught with pitfalls, and unsafe for human use. In this review, I describe how iPSCs are being triumphantly used to lay foundation for a fully functional discipline of regenerative dentistry and medicine, alongside discussing the challenges of translating therapies into clinics. I also discuss their future implications in regenerative dentistry field.

Highlights

  • The discovery of Embryonic Stem Cells (ESCs) [1,2,3] incited the search for discovering artificial differentiation techniques to confer the properties of ESCs onto somatic cells by altering epigenomic activity, such that the derived cells are pluripotent and capable of giving rise to embryonic-like stem cells

  • HiPSCs can be and stably passaged by dissociating the cells into single cells for long periods, without any chromosomal/karyotype abnormalities. Human induced pluripotent stem cells (hiPSCs) could be generated under feeder-free and xeno-free culture systems from human skin fibroblasts and blood cells, and they possessed differentiation abilities. These results indicate that hiPSCs can be generated and maintained under this novel culture system making them ideal for cell transplantation in humans

  • It may be convenient to apply these consistently demonstrated that oral mucosa, including gingival tissue, has enhanced wound healing cells to achieve the regeneration of complicated tissues/organs, such as the tooth and salivary gland, capability compare to skin [140,141], even though both tissue types share similar healing processes and which are formed through the interaction of epithelial and mesenchymal tissues sequences

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Summary

Introduction

The discovery of Embryonic Stem Cells (ESCs) [1,2,3] incited the search for discovering artificial differentiation techniques to confer the properties of ESCs onto somatic cells by altering epigenomic activity, such that the derived cells are pluripotent and capable of giving rise to embryonic-like stem cells These techniques are collectively referred to as cellular reprogramming. “Yamanaka’s cocktail” [5], or by independently determined combination of lentivirally transduced genes Oct3/4, Sox, NANOG (Nanoghomeobox), and Lin28 [4,6,7] While these reprogrammed cells have similar developmental potential as authentic hESCs, they come without the baggage of morality and ethics, as they are not derived from human embryos and the possibility of immune rejection from allogeneic transplantation.

Factors of Importance in the Generation of iPSCs
A Novel Culture System for iPSCs Derivation
Applications of iPSCs
Disease Remodelling
Regenerative Medicine
First ever Clinical Trial
Ongoing Clinical Trials
Development of iPSC Library
Choosing an Appropriate Somatic Cell Type
Variability and Heterogeneity
Validation of Pre-Clinical iPSC Therapies
Regulatory and Commercial Hurdles
Gingiva as an iPSC Source
Periodontal
Findings
Concluding Remarks and Future Perspectives
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