Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants.
De novo lymphangiogenesis influences the course of different human diseases as diverse as chronic renal transplant rejection and tumor metastasis. 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.
Kerjaschki
Dontscho
D
Department of Pathology, Medical University of Vienna - Allgemeines Krankenhaus Währinger Gürtel 18 - 20, A 1090 Vienna, Austria. dontscho.kerjaschki@meduniwien.ac.at
Huttary
Nicole
N
Raab
Ingrid
I
Regele
Heinz
H
Bojarski-Nagy
Katalin
K
Bartel
Gregor
G
Kröber
Stefan M
SM
Greinix
Hildegard
H
Rosenmaier
Agathe
A
Karlhofer
Franz
F
Wick
Nikolaus
N
Mazal
Peter R
PR
D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000473:pathology; D041322:Chromosomes, Human, Y; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016030:Kidney Transplantation / Q000009:adverse effects / Q000473:pathology*; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology; D014019:Tissue Donors; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics
D012333:RNA, Messenger; D040321:Vascular Endothelial Growth Factor Receptor-3