ABSTRACT
Arterial conduits are increasingly preferred for surgical bypass because of inherent functional properties conferred by arterial endothelial cells, especially nitric oxide production in response to physiologic stimuli. Here we tested whether endothelial progenitor cells (EPCs) can replace arterial endothelial cells and promote patency in tissue-engineered small-diameter blood vessels (4 mm). We isolated EPCs from peripheral blood of sheep, expanded them ex vivo and then seeded them on decellularized porcine iliac vessels. EPC-seeded grafts remained patent for 130 days as a carotid interposition graft in sheep, whereas non-seeded grafts occluded within 15 days. The EPC-explanted grafts exhibited contractile activity and nitric-oxide-mediated vascular relaxation that were similar to native carotid arteries. These results indicate that EPCs can function similarly to arterial endothelial cells and thereby confer longer vascular-graft survival. Due to their unique properties, EPCs might have other general applications for tissue-engineered structures and in treating vascular diseases.
Subject(s)
Blood Vessel Prosthesis , Endothelium, Vascular/cytology , Stem Cells/cytology , Animals , Blood Vessel Prosthesis Implantation , Cells, Cultured , Guinea Pigs , SheepABSTRACT
BACKGROUND: Previous tissue engineering approaches to create heart valves have been limited by the structural immaturity and mechanical properties of the valve constructs. This study used an in vitro pulse duplicator system to provide a biomimetic environment during tissue formation to yield more mature implantable heart valves derived from autologous tissue. METHODS AND RESULTS: Trileaflet heart valves were fabricated from novel bioabsorbable polymers and sequentially seeded with autologous ovine myofibroblasts and endothelial cells. The constructs were grown for 14 days in a pulse duplicator in vitro system under gradually increasing flow and pressure conditions. By use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and the valve constructs were implanted into 6 lambs (weight 19+/-2.8 kg). All animals had uneventful postoperative courses, and the valves were explanted at 1 day and at 4, 6, 8, 16, and 20 weeks. Echocardiography demonstrated mobile functioning leaflets without stenosis, thrombus, or aneurysm up to 20 weeks. Histology (16 and 20 weeks) showed uniform layered cuspal tissue with endothelium. Environmental scanning electron microscopy revealed a confluent smooth valvular surface. Mechanical properties were comparable to those of native tissue at 20 weeks. Complete degradation of the polymers occurred by 8 weeks. Extracellular matrix content (collagen, glycosaminoglycans, and elastin) and DNA content increased to levels of native tissue and higher at 20 weeks. CONCLUSIONS: This study demonstrates in vitro generation of implantable complete living heart valves based on a biomimetic flow culture system. These autologous tissue-engineered valves functioned up to 5 months and resembled normal heart valves in microstructure, mechanical properties, and extracellular matrix formation.
Subject(s)
Absorbable Implants , Culture Techniques/methods , Endothelium, Vascular/transplantation , Fibroblasts/transplantation , Heart Valve Prosthesis , Muscle, Smooth, Vascular/transplantation , Transplantation, Autologous/methods , Animals , Bioreactors , Echocardiography , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Extracellular Matrix/metabolism , Fibroblasts/cytology , Heart Valve Prosthesis Implantation , Muscle, Smooth, Vascular/cytology , Polymers , Sheep , Stress, Mechanical , Surface PropertiesABSTRACT
As the second leading cause of cancer-related deaths, colorectal cancer remains a significant health problem for American men and women. Advances in diagnosis, screening, surgical techniques, and adjuvant therapy have improved survival over the past 30 years. Although most novel therapies are in early stages of development, they offer potential for major advances in the management of colorectal cancer. Continued efforts focused on disease prevention, along with a better understanding of the tumor biology, cancer immunotherapy, and gene therapy will certainly yield more sophisticated and effective treatment strategies for all patients who are either at risk for or have already been diagnosed with colorectal cancer. As increasing numbers of clinicians, scientists, and health care professionals continue to address these issues, better interventions and therapies are likely to emerge.
Subject(s)
Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Chemotherapy, Adjuvant/methods , Clinical Protocols , Colectomy/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/mortality , Combined Modality Therapy , Female , Humans , Male , Neoplasm Staging , Prognosis , Radiotherapy, Adjuvant/methods , Survival Analysis , Treatment OutcomeABSTRACT
Chylothorax is an uncommon condition that may be associated with significant morbidity and mortality. The authors report a case of traumatic chylothorax attributed to child abuse and describe our management with tube thoracostomy and nutritional support with medium-chain triglycerides. Child abuse should be suspected in any case of chylothorax when no other etiology is evident and particularly when other signs of abuse are present.
