title: Hyaluronan based hydrogels provide an improved model to study megakaryocyte-matrix interactions.
abstract: Hyaluronan (HA) is a glycosamminoglican involved in cell biology as well as a relevant polymer for tissue engineering and regenerative medicine. Megakaryocytes (Mks) are immersed in a mesh of extracellular matrix (ECM) components that regulate their maturation in the bone marrow (BM) and the release of platelets into the bloodstream. While fibrous ECMs such as collagens and fibronectin have been demonstrated to differently regulate Mk function and platelet release, the role of HA, that fills the majority of the BM extracellular interstitial space, has not been investigated so far. Here we demonstrated that, although human Mks express HA receptors, they are not affected by HA in terms of in vitro differentiation, maturation and platelet formation. Importantly, chemical properties of HA were exploited to generate hydrogels with entrapped ECMs that represent a useful model to more closely mimic the tridimensional characteristics of the BM environment for studying Mk function. In conclusion, in this work we demonstrated that HA is an ideal candidate for a 3D ex vivo model of human BM ECM component environment.
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy; Laboratory of Biotechnology, IRCCS San Matteo Foundation, Pavia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Currao
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy; Laboratory of Biotechnology, IRCCS San Matteo Foundation, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malara
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy; Laboratory of Biotechnology, IRCCS San Matteo Foundation, Pavia, Italy.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Di Buduo
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy; Laboratory of Biotechnology, IRCCS San Matteo Foundation, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Abbonante
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy; Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Tozzi
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy; Laboratory of Biotechnology, IRCCS San Matteo Foundation, Pavia, Italy; Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA. Electronic address: alessandra.balduini@tufts.edu.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Balduini
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D021982:Cell-Matrix Junctions / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology*; D021621:Imaging, Three-Dimensional; D007527:Isoenzymes / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008954:Models, Biological; D008970:Molecular Weight; D034061:Thrombopoiesis / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D018960:Hyaluronan Receptors; D020100:Hydrogels; D007527:Isoenzymes; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases
keywords: Bone marrow; Extracellular matrix; Hyaluronic acid; Hydrogels; Megakaryocytes; Proplatelet formation; Proteoglycans; Thrombopoiesis