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Human mesenchymal stem cells pre-treated with IL-1β and stimulated with BMP-3 enhance chondrogenesis.

Journal article
Authors Daphne Hingert
Helena Barreto Henriksson
Helena Brisby
Published in Tissue engineering. Part A
Volume 24
Issue 9-10
ISSN 1937-335X
Publication year 2018
Published at Institute of Clinical Sciences, Department of Orthopaedics
Language en
Subject categories Cell biology, Cell and Molecular Biology, Basic Medicine


Low back pain is one of the most common ailments in western countries afflicting more than 80% of the population and the main cause is considered to be degeneration of intervertebral discs (IVDs). IL-1β is a vital inflammatory cytokine found in abundance in degenerated disc environment whereas BMP-3 is believed to promote chondrogenesis through TGF-β pathway.The aim was to study the effects of BMP-3, IL-1β and combination (pre-treatment with IL-1β) on hMSCs encapsulated in PuraMatrix™ hydrogel (Phg) especially in the absence of TGF-β in order to investigate the proliferation, and differentiation ability of hMSCs over 28 days period.100µL of hMSCs cell suspension was encapsulated between two layers of 100 µL hydrogels forming a sandwich-like structure. The encapsulated hMSCs were cultured in two sets of media, chondrogenic (C) and non-chondrogenic (nC) media along with addition of BMP-3 (10ng/mL) and IL-1β (10ng/mL). To study the combined effects of BMP-3 and IL-1β, the encapsulated hMSCs were first pre-treated with relevant media containing IL-1β for 24 hours, and then the media was replaced by media containing BMP-3 for the remaining experimental time period. IL-1β pre-treatment was carried out in both C and nC media. The samples were collected at day 7, 14, and 28.Proliferation and differentiation of hMSCs into chondrocyte-like cells was observed in all samples. Proteoglycans accumulation was observed in pre-treatment samples in C media. The protein and gene expression of Sox-9 and COL2A1 respectively, showed the occurrence of chondrogenesis in all samples.High cell viability, proliferation and differentiation was achieved in this in vitro model confirming that BMP-3 alone in the absence of TGF-β could drive hMSCs into chondrogenic lineage. Pre-treatment with IL-1β followed by BMP-3 stimulation resulted in high proteoglycans accumulation compared to stimulation with growth factors or cytokine alone. This suggests that pre-treatment with a pro-inflammatory cytokine before driving them into a chondrogeneic lineage might be of importance also in vivo.

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