Abstract
Background
A wealth of evidences have shown the participation and benefits of bone marrow-derived
mesenchymal stem cells (BM-MSCs) in wound healing and skin tissue repair in vivo. However, their role in epidermal development and reconstitution is not clearly investigated.
Objective
Here we examine the quantitative effect of human BM-MSCs on epidermal regeneration
in vitro.
Method
Human keratinocytes and BM-MSCs are cultured at ratios from 0% to 100% on top of a
fibroblast-embedded collagen gel in a three-dimensional organotypic co-culture model
at an air–liquid interface up to 20 days and analyzed by histochemical and immunochemical
staining of filaggrin, involucrin and keratin 10 on days 14 and 20. Human BM-MSCs
were tracked with quantum dots in organotypic co-cultures.
Results
It was found that epidermal development is strongly influenced by the percentage of
co-cultured BM-MSCs. A strong chemotactic effect between keratinocytes and MSCs was
seen in the group with 50% of BM-MSCs, which resulted in an impaired epidermal development,
whereas at a low percentage of BM-MSCs (10%), a stratified epidermal structure resembling
native skin was established on day 14 of culture. Moreover, the immunostaining studies
revealed that BM-MSCs in the low percentage (10%) participated in the basal periphery
of reconstructed epidermis and a similar pattern characteristic of native epidermis
was demonstrated in this experimental group, which was superior to all other experimental
groups in terms of the thickness of stratum corneum and the expression profile of
epidermal differentiation markers.
Conclusion
This study indicates the advantage of using a new skin equivalent model incorporating
a small fraction of MSCs to develop biologically useful tissues for maintaining homeostasis
during skin regeneration and wound healing process.
Abbreviations:
BM (bone marrow), MSCs (mesenchymal stem cells), BM-MSCs (bone marrow-derived mesenchymal stem cells), KERs (keratinocytes), DMEM (Dulbecco's modified Eagle's medium), FBS (fetal bovine serum), OC (organotypic co-culture), QDs (quantum dots), EGF (epidermal growth factor), VD3 (1,25 dihydroxyvitamin D3), 3D (three-dimensional), H&E (hematoxylin and eosin)Keywords
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Article info
Publication history
Published online: July 12, 2010
Accepted:
May 29,
2009
Received in revised form:
May 12,
2009
Received:
January 17,
2009
Identification
Copyright
© 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
