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Miniaturized 3D bone marrow tissue model to assess response to Thrombopoietin-receptor agonists in patients.
Di Buduo, Christian A; Laurent, Pierre-Alexandre; Zaninetti, Carlo; Lordier, Larissa; Soprano, Paolo M; Ntai, Aikaterini; Barozzi, Serena; La Spada, Alberto; Biunno, Ida; Raslova, Hana; Bussel, James B; Kaplan, David L; Balduini, Carlo L; Pecci, Alessandro; Balduini, Alessandra.
Afiliação
  • Di Buduo CA; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
  • Laurent PA; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
  • Zaninetti C; Department of Internal Medicine, I.R.C.C.S. San Matteo Foundation and the University of Pavia, Pavia, Italy.
  • Lordier L; UMR 1170, Institut National de la Santé et de la Recherche Médicale, Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy Cancer Campus, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, France.
  • Soprano PM; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
  • Ntai A; Integrated Systems Engineering, Milano, Italy.
  • Barozzi S; Isenet Biobanking, Milano, Italy.
  • La Spada A; Department of Internal Medicine, I.R.C.C.S. San Matteo Foundation and the University of Pavia, Pavia, Italy.
  • Biunno I; Integrated Systems Engineering, Milano, Italy.
  • Raslova H; Isenet Biobanking, Milano, Italy.
  • Bussel JB; Isenet Biobanking, Milano, Italy.
  • Kaplan DL; Institute for Genetic and Biomedical Research-CNR, Milano, Italy.
  • Balduini CL; UMR 1170, Institut National de la Santé et de la Recherche Médicale, Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy Cancer Campus, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, France.
  • Pecci A; Department of Pediatrics, Weill Cornell Medicine, New York, United States.
  • Balduini A; Department of Biomedical Engineering, Tufts University, Medford, United States.
Elife ; 102021 06 01.
Article em En | MEDLINE | ID: mdl-34059198
Platelets are tiny cell fragments essential for blood to clot. They are created and released into the bloodstream by megakaryocytes, giant cells that live in the bone marrow. In certain genetic diseases, such as Inherited Thrombocytopenia, the bone marrow fails to produce enough platelets: this leaves patients extremely susceptible to bruising, bleeding, and poor clotting after an injury or surgery. Certain patients with Inherited Thrombocytopenia respond well to treatments designed to boost platelet production, but others do not. Why these differences exist could be investigated by designing new test systems that recreate the form and function of bone marrow in the laboratory. However, it is challenging to build the complex and poorly understood bone marrow environment outside of the body. Here, Di Buduo et al. have developed an artificial three-dimensional miniature organ bioreactor system that recreates the key features of bone marrow. In this system, megakaryocytes were grown from patient blood samples, and hooked up to a tissue scaffold made of silk. The cells were able to grow as if they were in their normal environment, and they could shed platelets into an artificial bloodstream. After treating megakaryocytes with drugs to stimulate platelet production, Di Buduo et al. found that the number of platelets recovered from the bioreactor could accurately predict which patients would respond to these drugs in the clinic. This new test system enables researchers to predict how a patient will respond to treatment, and to tailor therapy options to each individual. This technology could also be used to test new drugs for Inherited Thrombocytopenias and other blood-related diseases; if scaled-up, it could also, one day, generate large quantities of lab-grown blood cells for transfusion.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazóis / Trombocitopenia / Benzoatos / Plaquetas / Células-Tronco Hematopoéticas / Megacariócitos / Trombopoese / Receptores de Trombopoetina / Nicho de Células-Tronco / Células-Tronco Pluripotentes Induzidas Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Elife Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Itália País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazóis / Trombocitopenia / Benzoatos / Plaquetas / Células-Tronco Hematopoéticas / Megacariócitos / Trombopoese / Receptores de Trombopoetina / Nicho de Células-Tronco / Células-Tronco Pluripotentes Induzidas Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Elife Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Itália País de publicação: Reino Unido