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Reprogramming of Keratinocytes as Donor or Target Cells Holds Great Promise for Cell Therapy and Regenerative Medicine

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Abstract

One of the most crucial branches of regenerative medicine is cell therapy, in which cellular material is injected into the patient to initiate the regenerative process. Cells obtained by reprogramming of the patient’s own cells offer ethical and clinical advantages could provide a new source of material for therapeutic applications. Studies to date have shown that only a subset of differentiated cell types can be reprogrammed. Among these, keratinocytes, which are the most abundant proliferating cell type in the epidermis, have gained increasing attention as both donor and target cells for reprogramming and have become a new focus of regenerative medicine. As target cells for the treatment of skin defects, keratinocytes can be differentiated or reprogrammed from embryonic stem cells, induced pluripotent stem cells, fibroblasts, adipose tissue stem cells, and mesenchymal cells. As donor cells, keratinocytes can be reprogrammed or direct reprogrammed into a number of cell types, including induced pluripotent stem cells, neural cells, and Schwann cells. In this review, we discuss recent advances in keratinocyte reprogramming, focusing on the induction methods, potential molecular mechanisms, conversion efficiency, and safety for clinical applications.

KCs as target cells can be reprogrammed or differentiated from fibroblasts, iPSCs, ATSCs, and mesenchymal cells. And as donor cells, KCs can be reprogrammed or directly reprogrammded into iPSCs, neural cells, Schwann cells, and epidermal stem cells.

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Abbreviations

ESCs:

embryonic stem cells

iPSCs:

induced pluripotent stem cells

ATSCs:

adipose tissue stem cells

KCs:

keratinocytes

RA:

retinoic acid

Bmp4:

bone morphogenetic protein 4

iKCs:

induced keratinocytes

RDEB:

recessive dystrophic epidermolysis bullosa

HFSCs:

Hair follicle stem cells

STEMCCA:

stem cell cassette

OSNL:

Oct4/Sox2/Nanog and Lin28

TCHH:

trichohyalin

BMMSCs:

bone marrow mesenchymal stem cells

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Acknowledgements

This work was supported by the National Nature Science Foundation of China (81571905, 81830064, 81721092), the National Key Research Development Plan (2017YFC1103300) and Military Logistics Research Key Project (AWS17J005).

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Authors and Affiliations

  1. School of Medicine, NanKai University, 94 Wei Jin Road, NanKai District, Tianjin, 300071, People’s Republic of China

    Yuehou Zhang

  2. Key Laboratory of Tissue Repair and Regeneration of PLA and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Fourth Medical Center of General Hospital of PLA, 51 Fu Cheng Road, HaiDian District, Beijing, 100048, People’s Republic of China

    Yuehou Zhang, Wenzhi Hu, Kui Ma, Cuiping Zhang & Xiaobing Fu

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Highlights

1. Studies to date have shown that only a subset of differentiated cell types can be reprogrammed.

2. Keratinocyte reprogramming have gained increasing attention as both donor and target cells.

3. We summarized the induction methods, mechanisms, efficiency and application safety.

4. This review can provide some implications for controlling the plasticity of differentiated cells.

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Zhang, Y., Hu, W., Ma, K. et al. Reprogramming of Keratinocytes as Donor or Target Cells Holds Great Promise for Cell Therapy and Regenerative Medicine. Stem Cell Rev and Rep 15, 680–689 (2019). https://doi.org/10.1007/s12015-019-09900-8

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  • DOI: https://doi.org/10.1007/s12015-019-09900-8

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