TY - JOUR
T1 - Bone Marrow-Derived Stem Cells Migrate into Intraepidermal Skin Defects of a Desmoglein-3 Knockout Mouse Model but Preserve their Mesodermal Differentiation
AU - Hünefeld, Christian
AU - Mezger, Markus
AU - Müller-Hermelink, Eva
AU - Schaller, Martin
AU - Müller, Ingo
AU - Amagai, Masayuki
AU - Handgretinger, Rupert
AU - Röcken, Martin
N1 - Funding Information:
MR has received grants (or other support as listed) from AB Science (Study), Abbott Laboratories (Study), Abbott Pharmaceuticals (Study), Almirall Hermal (Grant/Honorarium; Study and consulting), AstraZeneca (Study), Bayer (Study), Biogen Idec (Grant/Honorarium; Study, consulting and speaker), Bristol-Myers Squibb (Study), Bundesministerium für Bildung und Forschung (Research project), Celgene (Study), Deutsche Dermatologische Gesellschaft (Officer), Deutsche Forschungsgemeinschaft (Research project), Deutsche Krebshilfe (Research project), European Union (Research project), European Academy of Dermatology and Venereology (Officer), Galderma (Grant/Honorarium; Study and consulting), GSK (Study), Hokusai (Study), Janssen-Cilag (Grant/Honorarium; Study and consulting), Johnson & Johnson (Grant/Honorarium; Study and consulting), Lilly (Study), Merck (Study), MSD Sharp & Dohme (Study), Novartis (Study), Pfizer (Study), Philogen (Study), Regeneron (Honorarium; Consulting), Roche (Study), Sterna Biologicals (Honorarium; Speaker), Wilhelm Sander-Stiftung (Research project), Merck (Shareholder), BMS (Shareholder), Sanofi-Regeneron (Honorarium; Consulting), and IMPP (Honorarium; Consulting). The rest of the authors state no conflict of interest.
Funding Information:
We thank B. Fehrenbacher for her help with multicolor fluorescence microscopy, and K. Ghoreschi for preliminary analyses and discussions (all Department of Dermatology, Tübingen). This study was supported by research funding from the Federal Ministry for Education and Research (stem cell therapy for severe inherited skin fragility disorders, project number 01GN0972) and the Fortüne Program Tübingen (2021-0-0), DFG-TRR-156 and DFG (Ro764/14-1;764/15-1).
PY - 2018/5
Y1 - 2018/5
N2 - Inherited forms of epidermolysis bullosa are blistering diseases of the skin and mucosa resulting from various gene mutations. Transplantation of bone marrow-derived stem cells might be a promising systemic treatment for severe dystrophic or junctional epidermolysis bullosa, but many key questions remain unresolved. Two open questions of clinical interest are whether systemically transplanted bone marrow-derived stem cells of mesodermal origin might be able to transdifferentiate into keratinocytes with an ectodermal phenotype and whether these cells are also capable of repairing a specific intraepidermal gene defect. To address these questions, we transplanted bone marrow-derived stem cells into mice with a blistering disease exclusively localized to the epidermis resulting from a functional knockout of desmoglein-3 (Dsg3). We found that Dsg3+ donor-derived cells migrate into the recipient epidermis. However, these cells failed to restore the missing Dsg3 mRNA and DSG3 protein expression in the transplanted Dsg3–/– mice. The donor-derived cells found in the epidermis preserved their CD45+ hematopoietic origin, and no transdifferentiation into integrin α6+ keratinocytes or integrin α6+/CD34+ epidermal stem cells occurred. Our results indicate that bone marrow-derived stem cells preserve their mesodermal fate after systemic transplantation and are not capable of treating patients with epidermolysis bullosa with an intraepidermal skin defect.
AB - Inherited forms of epidermolysis bullosa are blistering diseases of the skin and mucosa resulting from various gene mutations. Transplantation of bone marrow-derived stem cells might be a promising systemic treatment for severe dystrophic or junctional epidermolysis bullosa, but many key questions remain unresolved. Two open questions of clinical interest are whether systemically transplanted bone marrow-derived stem cells of mesodermal origin might be able to transdifferentiate into keratinocytes with an ectodermal phenotype and whether these cells are also capable of repairing a specific intraepidermal gene defect. To address these questions, we transplanted bone marrow-derived stem cells into mice with a blistering disease exclusively localized to the epidermis resulting from a functional knockout of desmoglein-3 (Dsg3). We found that Dsg3+ donor-derived cells migrate into the recipient epidermis. However, these cells failed to restore the missing Dsg3 mRNA and DSG3 protein expression in the transplanted Dsg3–/– mice. The donor-derived cells found in the epidermis preserved their CD45+ hematopoietic origin, and no transdifferentiation into integrin α6+ keratinocytes or integrin α6+/CD34+ epidermal stem cells occurred. Our results indicate that bone marrow-derived stem cells preserve their mesodermal fate after systemic transplantation and are not capable of treating patients with epidermolysis bullosa with an intraepidermal skin defect.
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U2 - 10.1016/j.jid.2017.10.035
DO - 10.1016/j.jid.2017.10.035
M3 - Article
C2 - 29203359
AN - SCOPUS:85044781272
VL - 138
SP - 1157
EP - 1165
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 5
ER -