Shah Amita R, Cornejo Agustin, Guda Teja, Sahar David E, Stephenson Stacy M, Chang Shiliang, Krishnegowda Naveen K, Sharma Ramaswamy, Wang Howard T
From the *Division of Plastic and Reconstructive Surgery, University of Texas Health Science Center at San Antonio, †Department of Biomedical Engineering, University of Texas at San Antonio, and ‡Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
J Craniofac Surg. 2014 Jul;25(4):1504-9. doi: 10.1097/SCS.0000000000000755.
Critical-sized bone defects can lead to significant morbidity, and interventions are limited by the availability and donor-site morbidity of bone grafts. Polymer scaffolds seeded with cells have been explored to replace bone grafts. Adipose-derived stem cells have shown great promise for vascularization and osteogenesis of these constructs, and cocultures of differentiated stem cells are being explored to augment vessel and bone formation. Adipose-derived stem cells were differentiated into endothelial cells and osteoblasts, and in vitro studies showed increased proliferation of cocultured cells compared with undifferentiated adipose-derived stem cells and monocultures of endothelial cells and osteoblasts. The cells were seeded into polylactic acid gas-plasma-treated scaffolds as cocultures and monocultures and then implanted into critical-sized rat calvarial defects. The cocultures were in a 1:1 osteoblast to endothelial cell ratio. The increase in proliferation seen by the cocultured cells in vitro did not translate to increased vascularization and osteogenesis in vivo. In vivo, there were trends of increased vascularization in the endothelial cell group and increased osteogenesis in the osteoblast and endothelial monoculture groups, but no increase was seen in the coculture group compared with the undifferentiated adipose-derived stem cells. Endothelial cells enhance vascularization and osteoblast and endothelial cell monocultures enhance bone formation in the polymer scaffold. Predifferentiation of adipose-derived stem cells is promising for improving vascularization and osteogenesis in polymer scaffolds but requires future evaluation of coculture ratios to fully characterize this response.
临界尺寸的骨缺损可导致严重的发病率，而干预措施受到骨移植可用性和供体部位发病率的限制。已探索接种细胞的聚合物支架来替代骨移植。脂肪来源的干细胞在这些构建体的血管生成和成骨方面显示出巨大潜力，并且正在探索分化干细胞的共培养以增强血管和骨形成。脂肪来源的干细胞被分化为内皮细胞和成骨细胞，体外研究表明，与未分化的脂肪来源干细胞以及内皮细胞和成骨细胞的单培养相比，共培养细胞的增殖增加。将这些细胞以共培养和单培养的形式接种到经气体等离子体处理的聚乳酸支架中，然后植入临界尺寸的大鼠颅骨缺损处。共培养中，成骨细胞与内皮细胞的比例为1:1。共培养细胞在体外观察到的增殖增加并未转化为体内血管生成和成骨的增加。在体内，内皮细胞组有血管生成增加的趋势，成骨细胞和内皮细胞单培养组有骨生成增加的趋势，但与未分化的脂肪来源干细胞相比，共培养组未见增加。内皮细胞可增强聚合物支架中的血管生成，而成骨细胞和内皮细胞单培养可增强骨形成。脂肪来源干细胞的预分化有望改善聚合物支架中的血管生成和成骨，但需要进一步评估共培养比例以全面表征这种反应。
