Abstract
Backgroud
: More effective treatment strategies are needed for the chronic skin ulcers. Recently,
it has been reported that clinical application of stem cells improve wound healing.
Objective
We aimed to determine the dynamic time-course movement of epidermal stem cell markers
especially p75 neurotrophin receptor (p75NTR) and Integrin beta-1 in wound healing
process. Furthermore, we also investigated the presence of these markers in human.
Methods
Epidermal Integrin beta-1+ and p75NTR+ cells were counted in wound healing process in mice. Both cells were also counted
in human skin specimen obtained from chronic skin ulcers and healthy controls. Growth
factor gene expression levels by purified mouse epidermal p75NTR+ cells were also analyzed using real-time RT-PCR.
Results
Integrin beta-1+ and p75NTR+ cells were proliferated from 3 days after wounding. Reepithelization was completed
7 days after wounding, and the numbers of cells were returned to the baseline levels
by 14 days after wounding. Integrin beta-1+ cells were proliferated in the basal layer, and p75NTR+ cells were proliferated in the upper layer of epidermis. In human skin, Integrin
beta-1+ and p75NTR+ cells were 81% ± 12% and 36% ± 15% of the basal cells, respectively. In patients with chronic skin ulcers, the percentage
of Integrin beta-1+ cells in the epidermis was identical to healthy controls. Surprisingly, p75NTR+ cells were significantly decreased in chronic skin ulcer patients (1.2% ± 2.6%; p < 0.0005) compared to healthy controls. Purified mouse epidermal p75NTR+ cells expressed higher transforming growth factor-beta2 and vascular endothelial
growth factor-alpha transcripts and lower epidermal growth factor transcripts than
p75NTR− cells.
Conclusion
These results suggest that Integrin beta-1+ and p75NTR+ cells play an important role in wound healing process, and that p75NTR may be a key
molecule and a candidate for new therapeutic target besides preexisting molecules
for chronic skin ulcer patients.
Keywords
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Article info
Publication history
Published online: May 03, 2013
Accepted:
April 11,
2013
Received in revised form:
April 8,
2013
Received:
October 22,
2012
Identification
Copyright
© 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
