Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, California, USA.
Connect Tissue Res. 2011 Apr;52(2):109-18. doi: 10.3109/03008207.2010.484514. Epub 2010 Aug 11.
Recombinant human bone morphogenetic protein-2 (rhBMP2) has been shown to induce both in vitro osteogenic differentiation and in vivo bone formation, with the capacity of rhBMP2 to elicit the repair of numerous bony defects (calvaria, spinal fusion, femora, and so on) well documented. In addition, rhBMP2 has been approved by the Food and Drug Administration (FDA) for selected human indications. Despite the fact that healing is often achieved, the challenge still remains to optimize the therapeutic use of rhBMP2. One avenue may be through the combination of rhBMP2 with stem cells capable of osteogenic differentiation. This study investigates the ability of rhBMP2 at various doses in combination with human adipose-derived stem cells (ASCs) to heal critical-sized rat segmental femoral defects. For this, different doses of rhBMP2 were incorporated with apatite-coated porous poly(l-lactide-co-dl-lactide) (70 : 30) (PLDLA) scaffolds, seeded with ASCs, and implanted into athymic rats. After 8 weeks, all implants were harvested and processed for bone formation using micro computed tomography (microCT) analysis and histology. Despite the findings that indicate no adverse effect of the apatite surface on ASC osteogenesis, no significant difference in bone formation could be qualitatively or quantitatively determined upon the implantation of ASC-seeded scaffolds absorbed to increasing doses of rhBMP2. Such results would suggest that the presence of ASCs within rhBMP2-absorbed scaffolds does not improve the bone-forming ability of the construct and that the formation of bone may be driven by the rhBMP2 alone. Based on these results, the addition of ASCs to rhBMP2-treated scaffolds may provide no significant advantage in terms of the ability to heal bone.
重组人骨形态发生蛋白-2(rhBMP2)已被证明能诱导体外成骨分化和体内骨形成,rhBMP2 修复多种骨缺损(颅骨、脊柱融合、股骨等)的能力已有充分记录。此外,rhBMP2 已获得美国食品和药物管理局(FDA)批准用于特定的人体适应症。尽管已经实现了愈合,但仍然存在优化 rhBMP2 治疗用途的挑战。一种途径可能是将 rhBMP2 与具有成骨分化能力的干细胞结合使用。本研究调查了不同剂量的 rhBMP2 与人类脂肪来源干细胞(ASCs)结合使用以修复大鼠节段性股骨临界尺寸缺损的能力。为此,将不同剂量的 rhBMP2 与涂有磷灰石的多孔聚(L-乳酸-co-DL-乳酸)(70:30)(PLDLA)支架结合,接种 ASCs,并植入无胸腺大鼠体内。8 周后,所有植入物均被收获,并通过微计算机断层扫描(microCT)分析和组织学处理用于骨形成。尽管发现磷灰石表面对 ASC 成骨没有不良影响,但在植入吸收了不同剂量 rhBMP2 的 ASC 接种支架后,无论是定性还是定量,都不能确定骨形成有显著差异。这些结果表明,在 rhBMP2 吸收支架内存在 ASCs 并不能提高构建体的成骨能力,并且骨的形成可能仅由 rhBMP2 驱动。基于这些结果,在 rhBMP2 处理的支架中添加 ASCs 可能不会在愈合骨的能力方面提供显著优势。