Bone marrow stromal cells enhance the osteogenic properties of hydroxyapatite scaffolds by modulating the foreign body reaction

Abstract

We aimed to investigate the osteogenic properties of bone marrow stromal cell (BMSC)-loaded biomimetic constructs composed of hydroxyapatite (HA), with or without in vitro cell-derived extracellular matrix (HA-ECM), and to assess the cellular components of the elicited foreign body reaction. HA-ECM constructs were produced by adult rat dermal fibroblasts cultured on top of synthetic HA microparticles. Rat calvarial critical-sized defects (8 mm) were created and treated with the generated HA-ECM constructs or HA microparticles, alone or combined with green fluorescent protein (GFP)-expressing BMSCs. The new bone formation and the local cellular inflammatory response (macrophages, neutrophils, lymphocytes, eosinophils and PCNA-index) were assessed by histomorphometry and immunohistochemistry at 2 and 12 weeks postoperatively. In addition, the BMSCs' survival and engraftment were checked. The largest volume of the newly formed bone was found in defects treated with HA-ECM constructs combined with BMSCs (p < 0.05). Moreover, the implanted BMSCs modulated the local inflammatory response, demonstrated by either a significant increase (HA vs HA + BMSCs) or decrease (HA-ECM vs HA-ECM + BMSCs) of the inflammatory cell number. No donor BMSCs were detected at the site of implantation or in the host bone marrow at 2 or 12 weeks postoperatively. In conclusion, the treatment of critical-sized calvarial defects with the BMSC-loaded biomimetic constructs has significantly enhanced bone repair by modulating the foreign body reaction. Our findings highlight the implications of BMSCs in the regulation of the foreign body reaction triggered by tissue-engineered constructs, proving a higher efficiency for the BMSC combination therapy.

Development of a methacrylate-terminated PLGA copolymer for potential use in craniomaxillofacial fracture plates

“…Bone marrow-derived stromal cells (BMSCs) were isolated from adult male Sprague-Dawley rats as described previously [15] and used at passages 3 to 5. The experiment was approved by the Research Ethics Committee of Karolinska University Huddinge Hospital in accordance with the policy on human care and use of laboratory animals.…”

Acoustic tweezing cytometry enhances osteogenesis of human mesenchymal stem cells through cytoskeletal contractility and YAP activation

“…In particular, osteogenic differentiation of hMSCs in conjunction with tissue engineering methods have been exploited to provide an alternative approach besides autologous bone graft to replace or restore damaged bone tissues [2]. For example, biomimetic constructs composed hydroxyapatite (HA) and loaded with hMSCs have been shown to significantly enhance bone formation compared with HA alone at 12 weeks after surgery in vivo [3]. Cellular inflammatory response was less severe with hMSC loaded HA constructs compared with HA alone.…”

Role of Adult Tissue-Derived Pluripotent Stem Cells in Bone Regeneration

“…It has been shown previously that bone marrow-derived MSC are able to modulate foreign body reaction and interact with host immune cells during MSC-mediated bone formation [54] by attracting circulating hematopoietic stem cells and prompting their differentiation into M1 macrophages and osteoclasts [55]. A similar mechanism could be hypothesized for VSEL.…”