Abstract
BackgroundSkin is an organ that plays an important role as a physical barrier and has many other complex functions. Skin mimetics may be useful for studying the pathophysiology of diseases in vitro and for repairing lesions in vivo. Cord blood mononuclear cells (CBMCs) have emerged as a potential cell source for regenerative medicine. Human induced pluripotent stem cells (iPSCs) derived from CBMCs have great potential for allogenic regenerative medicine. Further study is needed on skin differentiation using CBMC-iPSCs.MethodsHuman iPSCs were generated from CBMCs by Sendai virus. CBMC-iPSCs were differentiated to fibroblasts and keratinocytes using embryonic body formation. To generate CBMC-iPSC-derived 3D skin organoid, CBMC-iPSC-derived fibroblasts were added into the insert of a Transwell plate and CBMC-iPSC-derived keratinocytes were seeded onto the fibroblast layer. Transplantation of 3D skin organoid was performed by the tie-over dressing method.ResultsEpidermal and dermal layers were developed using keratinocytes and fibroblasts differentiated from cord blood-derived human iPSCs, respectively. A complex 3D skin organoid was generated by overlaying the epidermal layer onto the dermal layer. A humanized skin model was generated by transplanting this human skin organoid into SCID mice and effectively healed skin lesions.ConclusionsThis study reveals that a human skin organoid generated using CBMC iPSCs is a novel tool for in-vitro and in-vivo dermatologic research.
Highlights
Skin is an organ that plays an important role as a physical barrier and has many other complex functions
A scheme of the fibroblast differentiation protocol is shown in Fig. 1a (n = 5 Cord blood mononuclear cell (CBMC)-derived Induced pluripotent stem cell (iPSC) lines per experiment)
We confirmed that CBMC-derived iPSCs can differentiate into keratinocytes and fibroblasts, the main cellular components of human skin. iPSC-derived fibroblast (iPSC-F) responded to a profibrotic agent and confirmed the effects of an antifibrotic drug
Summary
Skin is an organ that plays an important role as a physical barrier and has many other complex functions. Cord blood mononuclear cells (CBMCs) have emerged as a potential cell source for regenerative medicine. Human induced pluripotent stem cells (iPSCs) derived from CBMCs have great potential for allogenic regenerative medicine. Further study is needed on skin differentiation using CBMC-iPSCs. Skin, the largest organ, covers the exterior of the body and protects internal organs. The largest organ, covers the exterior of the body and protects internal organs It has diverse functions and is involved in protection against pathogens, storage of water, regulation of body temperature, and excretion of body waste [1, 2]. Human induced pluripotent stem cells (iPSCs) are emerging as a promising alternative in this regard [6,7,8]. Reprogrammed iPSCs overcome the ethical and immunological issues associated with embryonic stem cells (ESCs) and can differentiate into multiple lineages
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