Bioengineered vascular grafts: can we make them off-the-shelf?

Surgical treatments for vascular disease have progressed during the past century from autologous bypass conduits to synthetic materials, animal-derived tissues, cryopreserved grafts, and, finally, bioengineered conduits. In all cases, alternative vascular grafting materials have been developed with the goal of treating patients who have severe vascular disease requiring bypass but who have no suitable autologous conduit. Synthetic vascular grafts, animal-derived tissues, and cryopreserved grafts all have drawbacks in terms of availability and functionality that have limited their routine clinical adoption.

Readily available tissue-engineered vascular grafts.

Autologous or synthetic vascular grafts are used routinely for providing access in hemodialysis or for arterial bypass in patients with cardiovascular disease. However, some patients either lack suitable autologous tissue or cannot receive synthetic grafts. Such patients could benefit from a vascular graft produced by tissue engineering.

Relevance and safety of telomerase for human tissue engineering.

Tissue engineering holds the promise of replacing damaged or diseased tissues and organs. The use of autologous donor cells is often not feasible because of the limited replicative lifespan of cells, particularly those derived from elderly patients. Proliferative arrest can be overcome by the ectopic expression of telomerase via human telomerase reverse transcriptase (hTERT) gene transfection.

Phosphorylation and binding of AUF1 to the 3'-untranslated region of cardiomyocyte SERCA2a mRNA.

Experimental animals and patients with cardiac hypertrophy and heart failure display abnormally slowed myocardial relaxation, which is associated with downregulation of sarco(endo)plasmic reticulum calcium ATPase 2a (SERCA2a), the cardiomyocyte sarcoplasmic reticulum Ca2+ pump. We previously showed that SERCA2a downregulation can be simulated in cultured neonatal rat ventricular myocytes (NRVM) by treatment with the hypertrophic agonist phorbol myristate acetate (PMA) or by overexpression of the novel protein kinase C (PKC) isoenzymes PKCdelta and PKCepsilon. PKC activation, in turn, decreased SERCA2a promoter activity and destabilized the SERCA2a mRNA.