Nature Medicine
- 12, 230 - 234 (2006)
Published online: 15 January 2006; | doi:10.1038/nm1340
Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplantsDontscho Kerjaschki1, Nicole Huttary1, Ingrid Raab1, Heinz Regele1, Katalin Bojarski-Nagy1, Gregor Bartel1, Stefan M Kröber2, Hildegard Greinix3, Agathe Rosenmaier3, Franz Karlhofer4, Nikolaus Wick1 & Peter R Mazal11
Department of Pathology, Medical University of Vienna - Allgemeines Krankenhaus Währinger Gürtel 18 - 20, A 1090 Vienna, Austria. 2
Department of Pathology, University of Tübingen, Liebermeisterstra e 8, D 72076 Tübingen Germany. 3
Austrian Bone Marrow Donor Registry, Florianigasse 38/12, A 1080 Vienna, Austria. 4
Department of Dermatology, Medical University of Vienna - Allgemeines Krankenhaus Währinger Gürtel 18 - 20, A 1090 Vienna, Austria.
Correspondence should be addressed to Dontscho Kerjaschki dontscho.kerjaschki@meduniwien.ac.at
De novo lymphangiogenesis influences the course of different human diseases as diverse as chronic renal transplant rejection1 and tumor metastasis2,
3. The cellular mechanisms of lymphangiogenesis in human diseases are currently unknown, and could involve division of local preexisting endothelial cells or incorporation of circulating progenitors. We analyzed renal tissues of individuals with gender-mismatched transplants who had transplant rejection and high rates of overall lymphatic endothelial proliferation as well as massive chronic inflammation. Donor-derived cells were detected by in situ hybridization of the Y chromosome. We compared these tissues with biopsies of essentially normal skin and intestine, and two rare carcinomas with low rates of lymphatic endothelial proliferation that were derived from individuals with gender-mismatched bone marrow transplants. Here, we provide evidence for the participation of recipient-derived lymphatic progenitor cells in renal transplants. In contrast, lymphatic vessels of normal tissues and those around post-transplant carcinomas did not incorporate donor-derived progenitors. This indicates a stepwise mechanism of inflammation-associated de novo lymphangiogenesis, implying that potential lymphatic progenitor cells derive from the circulation, transmigrate through the connective tissue stroma, presumably in the form of macrophages, and finally incorporate into the growing lymphatic vessel.
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