Abstract
In this study, the bone-regenerative potential of bioactive factors derived from adipose tissue, platelet-rich plasma (PRP) and conditioned medium from hypoxia-treated human telomerase immortalized bone-marrow-derived mesenchymal stem cells (hTERT-MSC) was investigated in vitro with the aim to develop cost-effective and efficient bone substitutes for optimized regeneration of bone defects. Adipose tissue was harvested from human donors undergoing reconstructive surgery, and adipose tissue extract (ATE) was prepared. Platelet lysates (PL) were produced by repeated freeze-thaw cycles of PRP, and hypoxia-conditioned medium (HCM) was obtained by culturing human telomerase immortalized bone-marrow-derived mesenchymal stromal cells for 5 days with 1% O2. Besides analysis by cytokine and angiogenesis arrays, ELISA was performed. Angiogenic potential was investigated in cocultures of bone-marrow-derived (BM)-MSC and human umbilical vein endothelial cells. Multiple angiogenic proteins and cytokines were detected in all growth factor mixtures. HCM and ATE contained high amounts of angiogenin and CCL2/MCP-1, whereas PL contained high amounts of IGFBP-1. Culturing cells with HCM and ATE significantly increased specific ALP activity of BM-MSC as well as tubule length and junctions of endothelial networks, indicating osteogenic and angiogenic stimulation. To achieve a synergism between chemoattractive potential and osteogenic and angiogenic differentiation capacity, a combination of different growth factors appears promising for potential clinical applications.
Highlights
Local bone loss that may arise from trauma, tumor, infection, periprosthetic osteolysis or congenital musculoskeletal disorders constitutes a major worldwide socioeconomic problem frequently requiring surgical intervention
PDGF-AA could be detected in Platelet lysates (PL) and adipose tissue extract (ATE), but not in hypoxia-conditioned medium (HCM)
As determined by enzyme-linked immunosorbent assays (ELISA), Tissue inhibitor of metalloproteinases 1 (TIMP-1) as angiogenesis suppressor was abundant in all three growth factor mixtures (Table 2)
Summary
Local bone loss that may arise from trauma, tumor, infection, periprosthetic osteolysis or congenital musculoskeletal disorders constitutes a major worldwide socioeconomic problem frequently requiring surgical intervention. Allo- or xenografts carry the risk of immunogenic rejection and the potential for disease transmission [2,3]. Artificial matrix materials based on e.g., calcium phosphates, bioglass, synthetic or biological polymers and composites were developed to overcome the drawbacks of auto-, allo- and xenografts [4,5,6,7,8,9]. For bone regeneration, the ingrowth of osteogenic cells, as well as blood vessels to ensure sufficient nutrient and oxygen supply, is important. With the aim of obtaining an osteoinductive and angiogenic effect, these materials are combined with growth factors and/or cells [10,11]. Simultaneous delivery of osteogenic and angiogenic factors may significantly enhance the success of bone repair therapies [10]
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