Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Grab, Anna Luise [VerfasserIn]   i
 Seckinger, Anja [VerfasserIn]   i
 Hose, Dirk [VerfasserIn]   i
 Cavalcanti-Adam, Elisabetta A. [VerfasserIn]   i
Titel:Hyaluronan hydrogels delivering BMP-6 for local targeting of malignant plasma cells and osteogenic differentiation of mesenchymal stromal cells
Verf.angabe:Anna Luise Grab, Anja Seckinger, Patrick Horn, Dirk Hose, Elisabetta Ada Cavalcanti-Adam
E-Jahr:2019
Jahr:11 July 2019
Umfang:13 S.
Fussnoten:Gesehen am 28.10.2019
Titel Quelle:Enthalten in: Acta biomaterialia
Ort Quelle:[Amsterdam] : Elsevier, 2005
Jahr Quelle:2019
Band/Heft Quelle:96(2019), Seite 258-270
ISSN Quelle:1878-7568
Abstract:Multiple myeloma is a malignant disease characterized by accumulation of clonal plasma cells in the bone marrow. Uncoupling of bone formation and resorption by myeloma cells leads to osteolytic lesions. These are prone to fracture and represent a possible survival space for myeloma cells under treatment causing disease relapse. Here we report on a novel approach suitable for local treatment of multiple myeloma based on hyaluronic acid (HA) hydrogels mimicking the physical properties of the bone marrow. The HA hydrogels are complexed with heparin to achieve sustained presentation and controlled release of bone morphogenetic protein 6 (BMP-6). Others and we have shown that BMP-6 induces myeloma cell apoptosis and bone formation. Using quartz crystal microbalance and enzyme-linked immunosorbent assay, we measured an initial surface density of 400ng BMP6/cm2, corresponding to two BMP-6 per heparin molecule, with 50% release within two weeks. HA-hydrogels presenting BMP-6 enhanced the phosphorylation of Smad 1/5 while reducing the activity of BMP-6 antagonist sclerostin. These materials induced osteogenic differentiation of mesenchymal stromal cells and decreased the viability of myeloma cell lines and primary myeloma cells. BMP-6 functionalized HA-hydrogels represent a promising material for local treatment of myeloma-induced bone disease and residual myeloma cells within lesions to minimize disease relapse or fractures. - Statement of Significance - Multiple myeloma is a hematological cancer characterized by the accumulation of clonal plasma cells in the bone marrow and local suppression of bone formation, resulting in osteolytic lesions and fractures. Despite recent advances in systemic treatment of multiple myeloma, it is rare to achieve a targeted suppression of myeloma cells and healing of bone lesions. Here we present hydrogels which mimic the physico-chemical properties of the bone marrow, consisting of hyaluronic acid with crosslinked heparin for the controlled presentation of bioactive BMP-6. The hydrogels decrease the viability of myeloma cell lines and primary myeloma cells and induces osteogenic differentiation of mesenchymal stromal cells. The presentation of BMP-6 in the hyaluronan hydrogels enhances the phosphorylation of Smad1/5 while reducing the activity of the BMP-6 antagonist sclerostin. As such, BMP-6 functionalized hyaluronan hydrogels represent a promising material for the localized eradication of myeloma cells.
DOI:doi:10.1016/j.actbio.2019.07.018
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.actbio.2019.07.018
 Verlag: http://www.sciencedirect.com/science/article/pii/S1742706119304982
 DOI: https://doi.org/10.1016/j.actbio.2019.07.018
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:BMP-6
 BMP/Smad signaling
 Hyaluronan hydrogel
 Multiple myeloma
 Osteogenic differentiation
K10plus-PPN:1680038761
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68446644   QR-Code
zum Seitenanfang