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Adenoviral Mediated...
Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation
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Sharma, Sunita (författare)
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Sapkota, Dipak (författare)
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Xue, Ying (författare)
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- Sun, Yang (författare)
- KTH,Fiber- och polymerteknologi,Univ Bergen, Norway
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- Finne Wistrand, Anna, 1976- (författare)
- KTH,Fiber- och polymerteknologi
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Bruland, Ove (författare)
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Mustafa, Kamal (författare)
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(creator_code:org_t)
- 2016-01-25
- 2016
- Engelska.
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
- Relaterad länk:
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https://doi.org/10.1...
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactideco-epsilon-caprolactone){poly(LLA-co-CL)} scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.
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