Best Cameron, Tara Shuhei, Wiet Matthew, Reinhardt James, Pepper Victoria, Ball Matthew, Yi Tai, Shinoka Toshiharu, Breuer Christopher
Tissue Engineering and Surgical Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States.
Department of Cardiovascular Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, Japan.
ACS Biomater Sci Eng. 2017;3(9):1972-1979. doi: 10.1021/acsbiomaterials.6b00123. Epub 2016 Aug 8.
Stenosis limits widespread use of tissue-engineered vascular grafts (TEVGs), and bone marrow mononuclear cell (BM-MNC) seeding attenuates this complication. Yet seeding is a multistep process, and the singular effects of each component are unknown. We investigated which components of the clinical seeding protocol confer graft patency and sought to identify the optimal MNC source. Scaffolds composed of polyglycolic acid and -caprolactone/-lactic acid underwent conditioned media (CM) incubation ( = 25) and syngeneic BM-MNC ( = 9) or peripheral blood (PB)-MNC ( = 20) seeding. TEVGs were implanted for 2 weeks in the mouse IVC. CM incubation and PB-MNC seeding did not increase graft patency compared to control scaffolds prewet with PBS ( = 10), while BM-MNC seeding reduced stenosis by suppressing inflammation and smooth muscle cell, myofibroblast, and pericyte proliferation. IL-1, IL-6, and TNF were elevated in the seeded BM-MNC supernatant. Further, BM-MNC seeding reduced platelet activation in a dose-dependent manner, possibly contributing to TEVG patency.
狭窄限制了组织工程血管移植物(TEVG)的广泛应用,而骨髓单个核细胞(BM-MNC)接种可减轻这一并发症。然而,接种是一个多步骤过程,每个成分的单独作用尚不清楚。我们研究了临床接种方案中的哪些成分能赋予移植物通畅性,并试图确定最佳的单个核细胞来源。由聚乙醇酸和己内酯/乳酸组成的支架进行条件培养基(CM)孵育(n = 25),并接种同基因BM-MNC(n = 9)或外周血(PB)-MNC(n = 20)。将TEVG植入小鼠下腔静脉2周。与用PBS预湿的对照支架(n = 10)相比,CM孵育和PB-MNC接种并未提高移植物通畅性,而BM-MNC接种通过抑制炎症以及平滑肌细胞、肌成纤维细胞和周细胞增殖来减少狭窄。接种的BM-MNC上清液中白细胞介素-1、白细胞介素-6和肿瘤坏死因子升高。此外,BM-MNC接种以剂量依赖的方式降低血小板活化,这可能有助于TEVG通畅。