Higgins Steven P, Solan Amy K, Niklason Laura E
Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina 27708, USA.
J Biomed Mater Res A. 2003 Oct 1;67(1):295-302. doi: 10.1002/jbm.a.10599.
Polyglycolic acid (PGA) is commonly used as a scaffold for tissue engineering. Recent studies utilized PGA as a scaffold for vascular tissue engineering using bovine and porcine smooth muscle cells (SMCs). In engineered vessels, the SMCs displayed high rates of mitosis and dedifferentiation in areas where PGA fragments were present. We hypothesized that PGA breakdown products, sequestered within a SMC vessel at the conclusion of culture, led to increased proliferation and dedifferentiation of vascular SMCs. To test this hypothesis, the current study assessed possible means by which PGA breakdown products could lead to changes in SMC phenotype. SMCs grown in high concentrations of PGA breakdown products showed, by Western blotting, decreased expression of calponin, a marker for SMC differentiation. The same was true for SMCs grown in glycolic acid (GA), which also showed decreased expression of proliferating cell nuclear antigen (PCNA), a marker for SMC proliferation. In contrast, cells grown in varying amounts of NaCl or HCl showed little change in differentiation. We conclude that, independent of acidity or osmolality, plausible products of PGA degradation appear to induce dedifferentiation of porcine SMCs in vitro. Because of dedifferentiation and decreased mitosis, commercially available PGA may not represent an optimal scaffold for vascular tissue engineering.
聚乙醇酸(PGA)通常用作组织工程的支架。最近的研究将PGA用作使用牛和猪平滑肌细胞(SMC)进行血管组织工程的支架。在工程血管中,SMC在存在PGA片段的区域显示出高有丝分裂率和去分化。我们假设在培养结束时隔离在SMC血管内的PGA分解产物导致血管SMC的增殖增加和去分化。为了验证这一假设,当前研究评估了PGA分解产物可能导致SMC表型变化的方式。通过蛋白质印迹法,在高浓度PGA分解产物中生长的SMC显示,作为SMC分化标志物的钙调蛋白表达降低。在乙醇酸(GA)中生长的SMC也是如此,其增殖细胞核抗原(PCNA)作为SMC增殖标志物的表达也降低。相比之下,在不同量的NaCl或HCl中生长的细胞在分化方面几乎没有变化。我们得出结论,与酸度或渗透压无关,PGA降解的可能产物似乎在体外诱导猪SMC去分化。由于去分化和有丝分裂减少,市售的PGA可能不是血管组织工程的最佳支架。