Document Detail

Analysis of chemotactic molecules in bone marrow-derived mesenchymal stem cells and the skin: Ccl27-Ccr10 axis as a basis for targeting to cutaneous tissues.
MedLine Citation:
PMID:  23321329     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AIMS: Adult stem cells produce a plethora of extracellular matrix molecules and have a high potential as cell-based therapeutics for connective tissue disorders of the skin. However, the primary challenge of the stem cell-based approach is associated with the inefficient homing of systemically infused stem cells to the skin.
METHODS: We examined chemotactic mechanisms that govern directional migration of mesenchymal stem cells (MSCs) into the skin by conducting a comprehensive expression analysis of chemotactic molecules in MSCs and defined cutaneous tissues from normal and hereditary epidermolysis bullosa (EB)-affected skin.
RESULTS: Analysis of chemokine receptors in short-term and long-term MSC cultures showed tissue culture-dependent expression of several receptors. Assessment of epidermis-derived and dermis-derived chemokines showed that most chemotactic signals that originate from the skin preferentially recruit different sets of leukocytes rather than MSCs. Analysis of the chemotactic molecules derived from EB-affected non-blistered skin showed only minor changes in expression of selected chemokines and receptors. Nevertheless, the data allowed us to define the Ccl27-Ccr10 chemotactic axis as the most potent for the recruitment of MSCs to the skin. Our in vivo analysis demonstrated that uniform expression of Ccr10 on MSCs and alteration of Ccl27 level in the skin enhance extravasation of stem cells from circulation and facilitate their migration within cutaneous tissue.
CONCLUSIONS: Collectively, our study provides a comprehensive analysis of chemotactic signals in normal and EB-affected skin and proof-of-concept data demonstrating that alteration of the chemotactic pathways can enhance skin homing of the therapeutic stem cells.
Vitali Alexeev; Adele Donahue; Jouni Uitto; Olga Igoucheva
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cytotherapy     Volume:  15     ISSN:  1477-2566     ISO Abbreviation:  Cytotherapy     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-09-04     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  100895309     Medline TA:  Cytotherapy     Country:  England    
Other Details:
Languages:  eng     Pagination:  171-184.e1     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Bone Marrow Cells / cytology,  metabolism*
Cells, Cultured
Chemokine CCL27 / genetics,  metabolism*
Chemokines / metabolism
Epidermolysis Bullosa
Gene Expression Regulation
Mesenchymal Stromal Cells / cytology,  metabolism*
Receptors, CCR10 / genetics,  metabolism*
Receptors, Chemokine / metabolism
Skin / cytology,  metabolism*
Grant Support
Reg. No./Substance:
0/Ccl27 protein, mouse; 0/Ccr10 protein, mouse; 0/Chemokine CCL27; 0/Chemokines; 0/Receptors, CCR10; 0/Receptors, Chemokine

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