Bone Marrow-Derived Stem Cells Migrate into Intraepidermal Skin Defects of a Desmoglein-3 Knockout Mouse Model but Preserve their Mesodermal Differentiation

Christian Hünefeld, Markus Mezger, Eva Müller-Hermelink, Martin Schaller, Ingo Müller, Masayuki Amagai, Rupert Handgretinger, Martin Röcken

研究成果: Article査読

5 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1157-1165
ページ数9
ジャーナルJournal of Investigative Dermatology
138
5
DOI
出版ステータスPublished - 2018 5月

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学
  • 細胞生物学

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