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Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging.
Li, Jin; Carrillo García, Carmen; Riedt, Tamara; Brandes, Maria; Szczepanski, Sabrina; Brossart, Peter; Wagner, Wolfgang; Janzen, Viktor.
Afiliación
  • Li J; Department of Internal Medicine III, Division of Hematology/Oncology, University of Bonn, Bonn, Germany.
  • Carrillo García C; Department of Internal Medicine III, Division of Hematology/Oncology, University of Bonn, Bonn, Germany.
  • Riedt T; Department of Internal Medicine III, Division of Hematology/Oncology, University of Bonn, Bonn, Germany.
  • Brandes M; Department of Internal Medicine III, Division of Hematology/Oncology, University of Bonn, Bonn, Germany.
  • Szczepanski S; Department of Internal Medicine III, Division of Hematology/Oncology, University of Bonn, Bonn, Germany.
  • Brossart P; Department of Internal Medicine III, Division of Hematology/Oncology, University of Bonn, Bonn, Germany.
  • Wagner W; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.
  • Janzen V; Department of Internal Medicine III, Division of Hematology/Oncology, University of Bonn, Bonn, Germany. Viktor.Janzen@ukb.uni-bonn.de.
Sci Rep ; 8(1): 2833, 2018 02 12.
Article en En | MEDLINE | ID: mdl-29434282
In adult mammals, hematopoietic stem cells (HSCs) reside in the bone marrow and are in part regulated by the bone marrow microenvironment, called the stem cell niche. We have previously identified the bone marrow morphogen osteopontin (OPN), which is abundantly present in the bone marrow extracellular matrix, as a negative regulator of the size of the HSC pool under physiological conditions. Here, we study the impact of OPN on HSC function during aging using an OPN-knockout mouse model. We show that during aging OPN deficiency is associated with an increase in lymphocytes and a decline in erythrocytes in peripheral blood. In a bone marrow transplantation setting, aged OPN-deficient stem cells show reduced reconstitution ability likely due to insufficient differentiation of HSCs into more mature cells. In serial bone marrow transplantation, aged OPN-/- bone marrow cells fail to adequately reconstitute red blood cells and platelets, resulting in severe anemia and thrombocytopenia as well as premature deaths of recipient mice. Thus, OPN has different effects on HSCs in aged and young animals and is particularly important to maintain stem cell function in aging mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trombocitopenia / Envejecimiento / Células Madre Hematopoyéticas / Osteopontina / Anemia Límite: Animals Idioma: En Revista: Sci Rep Año: 2018 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trombocitopenia / Envejecimiento / Células Madre Hematopoyéticas / Osteopontina / Anemia Límite: Animals Idioma: En Revista: Sci Rep Año: 2018 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido