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dc.contributor.authorLui, Hayman
dc.contributor.authorDenbeigh, Janet
dc.contributor.authorVaquette, Cedryck
dc.contributor.authorTran, Hoai My
dc.contributor.authorDietz, Allan B
dc.contributor.authorCool, Simon M
dc.contributor.authorDudakovic, Amel
dc.contributor.authorKakar, Sanjeev
dc.contributor.authorvan Wijnen, Andre J
dc.date.accessioned2021-09-08T00:03:56Z
dc.date.available2021-09-08T00:03:56Z
dc.date.issued2021
dc.identifier.issn0378-1119
dc.identifier.doi10.1016/j.gene.2021.145662
dc.identifier.urihttp://hdl.handle.net/10072/407741
dc.description.abstractIntroduction: Culture conditions and differentiation cocktails may facilitate cell maturation and extracellular matrix (ECM) secretion and support the production of engineered fibroblastic tissues with applications in ligament regeneration. The objective of this study is to investigate the potential of two connective tissue-related ligands (i.e., BMP6 and GDF5) to mediate collagenous ECM synthesis and tissue maturation in vitro under normoxic and hypoxic conditions based on the hypothesis that BMP6 and GDF5 are components of normal paracrine signalling events that support connective tissue homeostasis. Methods: Human adipose-derived MSCs were seeded on 3D-printed medical-grade polycaprolactone (PCL) scaffolds using a bioreactor and incubated in media containing GDF5 and/or BMP6 for 21 days in either normoxic (5% oxygen) or hypoxic (2% oxygen) conditions. Constructs were harvested on Day 3 and 21 for cell viability analysis by live/dead staining, structural analysis by scanning electron microscopy, mRNA levels by RTqPCR analysis, and in situ deposition of proteins by immunofluorescence microscopy. Results: Pro-fibroblastic gene expression is enhanced by hypoxic culture conditions compared to normoxic conditions. Hypoxia renders cells more responsive to treatment with BMP6 as reflected by increased expression of ECM mRNA levels on Day 3 with sustained expression until Day 21. GDF5 was not particularly effective either in the absence or presence of BMP6. Conclusions: Fibroblastic differentiation of MSCs is selectively enhanced by BMP6 and not GDF5. Environmental factors (i.e., hypoxia) also influenced the responsiveness of cells to this morphogen.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherELSEVIER
dc.relation.ispartofjournalGene
dc.relation.ispartofvolume788
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchcode3105
dc.subject.fieldofresearchcode3208
dc.subject.fieldofresearchcode3207
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsGenetics & Heredity
dc.subject.keywordsLigament tissue engineering
dc.subject.keywords3D-printing
dc.titleFibroblastic differentiation of mesenchymal stem/stromal cells (MSCs) is enhanced by hypoxia in 3D cultures treated with bone morphogenetic protein 6 (BMP6) and growth and differentiation factor 5 (GDF5)
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationLui, H; Denbeigh, J; Vaquette, C; Tran, HM; Dietz, AB; Cool, SM; Dudakovic, A; Kakar, S; van Wijnen, AJ, Fibroblastic differentiation of mesenchymal stem/stromal cells (MSCs) is enhanced by hypoxia in 3D cultures treated with bone morphogenetic protein 6 (BMP6) and growth and differentiation factor 5 (GDF5), Gene, 2021, 788
dcterms.dateAccepted2021-04-15
dc.date.updated2021-09-07T22:20:44Z
gro.hasfulltextNo Full Text
gro.griffith.authorLui, Hayman H.


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