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dc.contributor.authorAng, Xiu Min-
dc.contributor.authorLee, Michelle H.C.-
dc.contributor.authorBlocki, Anna-
dc.contributor.authorChen, Clarice-
dc.contributor.authorOng, L.L. Sharon-
dc.contributor.authorAsada, H. Harry-
dc.contributor.authorSheppard, Allan-
dc.contributor.authorRaghunath, Michael-
dc.date.accessioned2018-10-26T13:47:49Z-
dc.date.available2018-10-26T13:47:49Z-
dc.date.issued2014-03-
dc.identifier.issn1937-335Xde_CH
dc.identifier.issn1937-3341de_CH
dc.identifier.urihttps://digitalcollection.zhaw.ch/handle/11475/12187-
dc.description.abstractThe microenvironment plays a vital role in both the maintenance of stem cells in their undifferentiated state (niche) and their differentiation after homing into new locations outside this niche. Contrary to conventional in-vitro culture practices, the in-vivo stem cell microenvironment is physiologically crowded. We demonstrate here that re-introducing macromolecular crowding (MMC) at biologically relevant fractional volume occupancy during chemically induced adipogenesis substantially enhances the adipogenic differentiation response of human bone marrow-derived mesenchymal stem cells (MSCs). Both early and late adipogenic markers were significantly up-regulated and cells accumulated 25-40% more lipid content under MMC relative to standard induction cocktails. MMC significantly enhanced deposition of extracellular matrix (ECM), notably collagen IV and perlecan, a heparan sulfate proteoglycan. As a novel observation, MMC also increased the presence of matrix metalloproteinase-2 in the deposited ECM, which was concomitant with geometrical ECM remodeling typical of adipogenesis. This suggested a microenvironment that was richer in both matrix components and associated ligands and was conducive to adipocyte maturation. This assumption was confirmed by seeding undifferentiated MSCs on decellularized ECM deposited by adipogenically differentiated MSCs, Adipo-ECM. On Adipo-ECM generated under crowding, MSCs differentiated much faster under a classical differentiation protocol. This was evidenced throughout the induction time course, by a significant up-regulation of both early and late adipogenic markers and a 60% higher lipid content on MMC-generated Adipo-ECM in comparison to standard induction on tissue culture plastic. This suggests that MMC helps build and endow the nascent microenvironment with adipogenic cues. Therefore, MMC initiates a positive feedback loop between cells and their microenvironment as soon as progenitor cells are empowered to build and shape it, and, in turn, are informed by it to respond by attaining a stable differentiated phenotype if so induced. This work sheds new light on the utility of MMC to tune the microenvironment to augment the generation of adipose tissue from differentiating human MSCs.de_CH
dc.language.isoende_CH
dc.publisherMary Ann Liebertde_CH
dc.relation.ispartofTissue Engineering - Part Ade_CH
dc.rightsLicence according to publishing contractde_CH
dc.subject.ddc571: Physiologie und verwandte Themende_CH
dc.subject.ddc616: Innere Medizin und Krankheitende_CH
dc.titleMacromolecular crowding amplifies adipogenesis of human bone marrow-derived MSCs by enhancing the pro-adipogenic microenvironmentde_CH
dc.typeBeitrag in wissenschaftlicher Zeitschriftde_CH
dcterms.typeTextde_CH
zhaw.departementLife Sciences und Facility Managementde_CH
zhaw.organisationalunitInstitut für Chemie und Biotechnologie (ICBT)de_CH
dc.identifier.doi10.1089/ten.tea.2013.0337de_CH
zhaw.funding.euNode_CH
zhaw.issue5-6de_CH
zhaw.originated.zhawNode_CH
zhaw.publication.statuspublishedVersionde_CH
zhaw.volume20de_CH
zhaw.publication.reviewPeer review (Publikation)de_CH
zhaw.webfeedMetabolic Tissue Engineeringde_CH
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Ang, X. M., Lee, M. H. C., Blocki, A., Chen, C., Ong, L. L. S., Asada, H. H., Sheppard, A., & Raghunath, M. (2014). Macromolecular crowding amplifies adipogenesis of human bone marrow-derived MSCs by enhancing the pro-adipogenic microenvironment. Tissue Engineering - Part A, 20(5-6). https://doi.org/10.1089/ten.tea.2013.0337
Ang, X.M. et al. (2014) ‘Macromolecular crowding amplifies adipogenesis of human bone marrow-derived MSCs by enhancing the pro-adipogenic microenvironment’, Tissue Engineering - Part A, 20(5-6). Available at: https://doi.org/10.1089/ten.tea.2013.0337.
X. M. Ang et al., “Macromolecular crowding amplifies adipogenesis of human bone marrow-derived MSCs by enhancing the pro-adipogenic microenvironment,” Tissue Engineering - Part A, vol. 20, no. 5-6, Mar. 2014, doi: 10.1089/ten.tea.2013.0337.
ANG, Xiu Min, Michelle H.C. LEE, Anna BLOCKI, Clarice CHEN, L.L. Sharon ONG, H. Harry ASADA, Allan SHEPPARD und Michael RAGHUNATH, 2014. Macromolecular crowding amplifies adipogenesis of human bone marrow-derived MSCs by enhancing the pro-adipogenic microenvironment. Tissue Engineering - Part A. März 2014. Bd. 20, Nr. 5-6. DOI 10.1089/ten.tea.2013.0337
Ang, Xiu Min, Michelle H.C. Lee, Anna Blocki, Clarice Chen, L.L. Sharon Ong, H. Harry Asada, Allan Sheppard, and Michael Raghunath. 2014. “Macromolecular Crowding Amplifies Adipogenesis of Human Bone Marrow-Derived MSCs by Enhancing the Pro-Adipogenic Microenvironment.” Tissue Engineering - Part A 20 (5-6). https://doi.org/10.1089/ten.tea.2013.0337.
Ang, Xiu Min, et al. “Macromolecular Crowding Amplifies Adipogenesis of Human Bone Marrow-Derived MSCs by Enhancing the Pro-Adipogenic Microenvironment.” Tissue Engineering - Part A, vol. 20, no. 5-6, Mar. 2014, https://doi.org/10.1089/ten.tea.2013.0337.


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