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Bilthoven, Netherlands

Schop D.,Xpand Biotechnology BV | Van Dijkhuizen-Radersma R.,Xpand Biotechnology BV | Van Dijkhuizen-Radersma R.,Progentix Orthobiology BV | Van Dijkhuizen-Radersma R.,Genmab | And 8 more authors.
Journal of Tissue Engineering and Regenerative Medicine | Year: 2010

Adult stem cells, or mesenchymal stromal cells (MSCs), are of great potential for cell therapy and tissue-engineering applications. However, for therapeutic use, these cells need to be isolated from tissue or a biopsy and efficiently expanded, as they cannot be harvested in sufficient quantities from the body. In our opinion, efficient expansion of MSCs can be achieved in a microcarrier-based cultivation system. This study selected a suitable microcarrier for human bone marrow-derived stromal cells (HBMSCs), optimized cell-seeding strategies by varying serum concentrations, and optimized dynamic expansion of the HBMSCs in a microcarrier-based spinner flask cultivation system by applying various feeding regimes. Cytodex 1 microcarriers in combination with a lowserum concentration (0-5%) in the medium resulted in the highest seeding efficiency for the HBMSCs. Subsequently, significant expansion of the HBMSCs on these carriers has been observed. The highest number of HBMSCs population doublings (4.8 doublings)was obtained by a combination of 50% medium refreshment combined with addition of 30% medium containing microcarriers every 3 days. Exponential cell growth was observed for at least 9 days after seeding, provided that sufficient nutrients (such as glucose) were present, metabolite concentrations (such as ammonia) were kept below growth-inhibitory concentrations and adequate surface area was present for the cells. After dynamic expansion of the HBMSCs, the cells retained their differentiation potential and their cell surface markers, indicating that HBMSCs expansion on Cytodex 1 microcarriers did not alter the phenotypic properties of the cells. Copyright © 2009 John Wiley & Sons, Ltd. Source

Yuan H.,Progentix Orthobiology BV | Yuan H.,University of Twente | Fernandes H.,University of Twente | Habibovic P.,University of Twente | And 7 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Biomaterials can be endowed with biologically instructive properties by changing basic parameters such as elasticity and surface texture. However, translation from in vitro proof of concept to clinical application is largely missing. Porous calcium phosphate ceramics are used to treat small bone defects but in general do not induce stem cell differentiation, which is essential for regenerating large bone defects. Here, we prepared calcium phosphate ceramics with varying physicochemical and structural characteristics. Microporosity correlated to their propensity to stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo. Implantation in a large bone defect in sheep unequivocally demonstrated that osteoinductive ceramics are equally efficient in bone repair as autologous bone grafts. Our results provide proof of concept for the clinical application of "smart" biomaterials. Source

Barradas A.M.C.,University of Twente | Yuan H.,University of Twente | Yuan H.,Progentix Orthobiology BV | van der Stok J.,Rotterdam University | And 8 more authors.
Biomaterials | Year: 2012

The efficacy of calcium phosphate (CaP) ceramics in healing large bone defects is, in general, not as high as that of autologous bone grafting. Recently, we reported that CaP ceramics with osteoinductive properties were as efficient in healing an ilium defect of a sheep as autologous bone graft was, which makes this subclass of CaP ceramics a powerful alternative for bone regeneration. Although osteoinduction by CaP ceramics has been shown in several large animal models it is sporadically reported in mice. Because the lack of a robust mouse model has delayed understanding of the mechanism, we screened mice from 11 different inbred mouse strains for their responsiveness to subcutaneous implantation of osteoinductive tricalcium phosphate (TCP). In only two strains (FVB and 129S2) the ceramic induced bone formation, and in particularly, in FVB mice, bone was found in all the tested mice. We also demonstrated that other CaP ceramics induced bone formation at the same magnitude as that observed in other animal models. Furthermore, VEGF did not significantly increase TCP induced bone formation. The mouse model here described can accelerate research of osteoinductive mechanisms triggered by CaP ceramics and potentially the development of therapies for bone regeneration. © 2012 Elsevier Ltd. Source

Van Gaalen S.M.,University Utrecht | Dhert W.J.A.,University Utrecht | Kruyt M.C.,University Utrecht | Yuan H.,University of Twente | And 5 more authors.
Tissue Engineering - Part A | Year: 2010

The aim of this study was to investigate the effect of implant location on bone formation in goats using autologous bone marrow-derived stromal cells in porous calcium phosphate scaffolds. Intramuscular locations were compared to posterolateral spine fusion locations in eight goats. As scaffolds, we used biphasic calcium phosphate porous blocks of 5×5×5mm. Cell-seeded implants were compared to empty controls. Bone marrow-derived stromal cells were seeded at 8 million cells per cm3 scaffold and cultured for 1 week. The follow-up time was 12 weeks. Fluorochromes were administered intravenously at 4, 6, and 8 weeks. Ectopic implants showed 21±3.6% bone formation for the cell seeded and 2.0±3.0% for the controls (p<0.001). Paraspinal implants, however, showed 0.10±0.13% in the cell seeded compared to 0.023±0.027% in the control group (p=0.09). A benefit of the cells was only found in the area closest to the paraspinal muscles (p<0.01). Bone formation in the control samples was of later onset compared to the cell-seeded implants. In conclusion, cell-based bone tissue engineering in an ectopic environment was clearly effective. Similar constructs implanted in a posterolateral spine fusion location hardly showed any effect. Copyright 2010, Mary Ann Liebert, Inc. Source

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