Fat-Derived Stromal Vascular Fraction Cells Enhance the Bone-Forming Capacity of Devitalized Engineered Hypertrophic Cartilage Matrix
Autor: | Alexander Haumer, Paul Bourgine, Matthias Kreutz, Ivan Martin, Celeste Scotti, Claude Jaquiery, Arnaud Scherberich, Andrea Barbero, Atanas Todorov |
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Rok vydání: | 2016 |
Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty Stromal cell 0206 medical engineering Mice Nude Osteoclasts Adipose tissue Cell Count 02 engineering and technology Choristoma Bone tissue Rats Nude 03 medical and health sciences Tissue engineering Osteogenesis Tissue Engineering and Regenerative Medicine medicine Animals Humans Cell Lineage Wound Healing Tissue Engineering Chemistry Cartilage Mesenchymal stem cell Endothelial Cells Hypertrophy Cell Biology General Medicine Anatomy Stromal vascular fraction 020601 biomedical engineering Extracellular Matrix 030104 developmental biology medicine.anatomical_structure Female Stromal Cells Wound healing Developmental Biology |
Zdroj: | Stem Cells Translational Medicine. 5:1684-1694 |
ISSN: | 2157-6580 2157-6564 |
Popis: | Abstract Engineered and devitalized hypertrophic cartilage (HC) has been proposed as bone substitute material, potentially combining the features of osteoinductivity, resistance to hypoxia, capacity to attract blood vessels, and customization potential for specific indications. However, in comparison with vital tissues, devitalized HC grafts have reduced efficiency of bone formation and longer remodeling times. We tested the hypothesis that freshly harvested stromal vascular fraction (SVF) cells from human adipose tissue—which include mesenchymal, endothelial, and osteoclastic progenitors—enhance devitalized HC remodeling into bone tissue. Human SVF cells isolated from abdominal lipoaspirates were characterized cytofluorimetrically. HC pellets, previously generated by human bone marrow-derived stromal cells and devitalized by freeze/thaw, were embedded in fibrin gel with or without different amounts of SVF cells and implanted either ectopically in nude mice or in 4-mm-diameter calvarial defects in nude rats. In the ectopic model, SVF cells added to devitalized HC directly contributed to endothelial, osteoblastic, and osteoclastic populations. After 12 weeks, the extent of graft vascularization and amount of bone formation increased in a cell-number-dependent fashion (up to, respectively, 2.0-fold and 2.9-fold using 12 million cells per milliliter of gel). Mineralized tissue volume correlated with the number of implanted, SVF-derived endothelial cells (CD31+ CD34+ CD146+). In the calvarial model, SVF activation of HC using 12 million cells per milliliter of gel induced efficient merging among implanted pellets and strongly enhanced (7.3-fold) de novo bone tissue formation within the defects. Our findings outline a bone augmentation strategy based on off-the-shelf devitalized allogeneic HC, intraoperatively activated with autologous SVF cells. Significance This study validates an innovative bone substitute material based on allogeneic hypertrophic cartilage that is engineered, devitalized, stored, and clinically used, together with autologous cells, intraoperatively derived from a lipoaspirate. The strategy was tested using human cells in an ectopic model and an orthotopic implantation model, in immunocompromised animals. |
Databáze: | OpenAIRE |
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