title: Hematopoietic bone marrow cells participate in endothelial, but not epithelial or mesenchymal cell renewal in adult rats.
abstract: The extent to which bone marrow (BM) contributes to physiological cell renewal is still controversial. Using the marker human placental alkaline phosphatase (ALPP) which can readily be detected in paraffin and plastic sections by histochemistry or immunohistochemistry, and in ultrathin sections by electron microscopy after pre-embedding staining, we examined the role of endogenous BM in physiological cell renewal by analysing tissues from lethally irradiated wild-type inbred Fischer 344 (F344) rats transplanted (BMT) with unfractionated BM from ALPP-transgenic F344 rats ubiquitously expressing the marker. Histochemical, immunohistochemical and immunoelectron microscopic analysis showed that the proportion of ALPP(+)  capillary endothelial cells (EC) profoundly increased from 1 until 6 months after BMT in all organs except brain and adrenal medulla. In contrast, pericytes and EC in large blood vessels were ALPP(-) . Epithelial cells in kidney, liver, pancreas, intestine and brain were recipient-derived at all time-points. Similarly, osteoblasts, chondrocytes, striated muscle and smooth muscle cells were exclusively of recipient origin. The lack of mesenchymal BM-derived cells in peripheral tissues prompted us to examine whether BMT resulted in engraftment of mesenchymal precursors. Four weeks after BMT, all haematopoietic BM cells were of donor origin by flow cytometric analysis, whereas isolation of BM mesenchymal stem cells (MSC) failed to show engraftment of donor MSC. In conclusion, our data show that BM is an important source of physiological renewal of EC in adult rats, but raise doubt whether reconstituted irradiated rats are an apt model for BM-derived regeneration of mesenchymal cells in peripheral tissues.
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Kathrin I
authors.initials: KI
authors.lastname: Odörfer
authors.forename: Monika
authors.initials: M
authors.lastname: Egerbacher
authors.forename: Nina J
authors.initials: NJ
authors.lastname: Unger
authors.forename: Karin
authors.initials: K
authors.lastname: Weber
authors.forename: Angelika
authors.initials: A
authors.lastname: Jamnig
authors.forename: Günter
authors.initials: G
authors.lastname: Lepperdinger
authors.forename: Miriam
authors.initials: M
authors.lastname: Kleiter
authors.forename: Eric P
authors.initials: EP
authors.lastname: Sandgren
authors.forename: Reinhold G
authors.initials: RG
authors.lastname: Erben
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000032:analysis / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D007928:Lethal Dose 50; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D014916:Whole-Body Irradiation
chemical_list: D058851:GPI-Linked Proteins; D007527:Isoenzymes; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental