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A Systematic Review of Stem Cell Differentiation into Keratinocytes for Regenerative Applications

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Abstract

To improve wound healing or treatment of other skin diseases, and provide model cells for skin biology studies, in vitro differentiation of stem cells into keratinocyte-like cells (KLCs) is very desirable in regenerative medicine. This study examined the most recent advancements in in vitro differentiation of stem cells into KLCs, the effect of biofactors, procedures, and preparation for upcoming clinical cases. A range of stem cells with different origins could be differentiated into KLCs under appropriate conditions. The most effective ways of stem cell differentiation into keratinocytes were found to include the co-culture with primary epithelial cells and keratinocytes, and a cocktail of growth factors, cytokines, and small molecules. KLCs should also be supported by biomaterials for the extracellular matrix (ECM), which replicate the composition and functionality of the in vivo extracellular matrix (ECM) and, thus, support their phenotypic and functional characteristics. The detailed efficient characterization of different factors, and their combinations, could make it possible to find the significant inducers for stem cell differentiation into epidermal lineage. Moreover, it allows the development of chemically known media for directing multi-step differentiation procedures.

In conclusion, the differentiation of stem cells to KLCs is feasible and KLCs were used in experimental, preclinical, and clinical trials. However, the translation of KLCs from in vitro investigational system to clinically valuable cells is challenging and extremely slow.

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Data Availability

The data will be available upon request.

Abbreviations

ASCs:

Adult stem cells

ADSCs:

Adipose-derived stem cells

BMP:

Bone morphogenic protein

CE:

Cornified cell envelope

DAPT:

γ-secretase inhibitor

DFs:

Dermal fibroblasts

ESCs:

Embryonic stem cells

EpiSCs:

Epidermal stem cells

EGF:

Epithelial growth factor

ECM:

Extracellular matrix

FCS:

Fetal calf serum

FSCs:

Fetal stem cells

FGF:

Fibroblast growth factor

HSCs:

Hematopoietic stem cells

hAFSC:

Human amniotic fluid stem cells

eiPSC:

Induced pluripotent stem cells

KGF:

Keratinocyte growth factor

KLCs:

Keratinocyte like cells

MenSCs:

Menstrual blood-derived stem cells

MSCs:

Mesenchymal stem cells

mPSCs:

Monkey pluripotent stem cells

NCDCs:

Neural crest-derived cells

PSCs:

Pluripotent stem cells

PCL:

Polycaprolactone

rADSCs:

Rabbit adipose-derived stem cells

rHFSCs:

Rat hair follicle stem cells

RA:

Retinoic acid

UCMSCs:

Umbilical cord mesenchymal stem cells

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Acknowledgements

The authors are grateful to report that this article is a part of the Ph.D. thesis and is supported by the Tabriz University of Medical Sciences (Pharmacy faculty- Medicinal Chemistry Department) with grant number 58491.

Funding

This work was supported by Tabriz University of Medical Sciences, grant number: 58491.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Raheleh Hazrati, Soodabeh Davaran & Somaieh Soltani

  2. Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Raheleh Hazrati & Soodabeh Davaran

  3. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Peyman Keyhanvar & Effat Alizadeh

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  1. Raheleh Hazrati
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  2. Soodabeh Davaran
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Contributions

R H: Conceptualization, Validation, Methodology, Formal analysis, Writing – original draft. S D, S S, P K: review &editing. EA: Conceptualization, Writing- reviewing and editing the final draft. All authors read and approved the final manuscript.

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Correspondence to Soodabeh Davaran or Effat Alizadeh.

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Hazrati, R., Davaran, S., Keyhanvar, P. et al. A Systematic Review of Stem Cell Differentiation into Keratinocytes for Regenerative Applications. Stem Cell Rev and Rep 20, 362–393 (2024). https://doi.org/10.1007/s12015-023-10636-9

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