Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation.

Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation.
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DOI:
10.1126/scitranslmed.aau6934
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发表时间:
2019-03-27
影响因子:
17.1
通讯作者:
Prichard HL
Prichard HL
中科院分区:
医学1区
文献类型:
--
作者:
Kirkton RD;Santiago-Maysonet M;Lawson JH;Tente WE;Dahl SLM;Niklason LE;Prichard HL

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由合成聚合物或身体人或动物组织构建的传统血管移植物支持临床对随时可用的血管的需求,但往往伴随着相关的风险。这些材料的组织病理学评估显示,由于不充分或不适当的基质重塑,宿主细胞发生了不良反应和/或机械降解。我们开发了一种研究用的生物工程人去细胞血管(HAV),目前正在研究作为终末期肾病患者的血液透析管道。在极少数情况下,在常规外科治疗过程中采集少量甲型肝炎病毒样本,用于检查植入后宿主细胞对甲型肝炎病毒反应的时间和空间模式,时间从16周到200周不等。我们观察到大量表达α-平滑肌肌动蛋白(α-SMA)的细胞进入甲型肝炎病毒,这些细胞逐渐成熟并在甲型肝炎病毒壁周向排列。这些细胞最初由新生外膜中的CD34+/CD31+细胞形成的微血管系统支持,后来由中膜和管腔中的CD34CD34/CD31+内皮细胞维持。Nestin+祖细胞分化为CD31SMA+或α+细胞,可能有助于甲型肝炎病毒早期再细胞化和自我修复。随着植入时间的延长,间充质干细胞样CD90+祖细胞数量增加。我们的结果表明,宿主HAVS的肌源性、内皮细胞和祖细胞的再繁殖将这些先前无细胞的血管转变为功能丰富的多层活组织,这些组织在插管损伤后维持血液运输和自我修复,有效地使这些血管像患者自己的血管一样。
Traditional vascular grafts constructed from synthetic polymers or cadaveric human or animal tissues support the clinical need for readily available blood vessels, but often come with associated risks. Histopathological evaluation of these materials has shown adverse host cellular reactions and/or mechanical degradation due to insufficient or inappropriate matrix remodeling. We developed an investigational bioengineered human acellular vessel (HAV), which is currently being studied as a hemodialysis conduit in patients with end-stage renal disease. In rare cases, small samples of HAV were recovered during routine surgical interventions and used to examine the temporal and spatial pattern of the host cell response to the HAV after implantation, from 16 to 200 weeks. We observed a substantial influx of alpha smooth muscle actin (αSMA)–expressing cells into the HAV that progressively matured and circumferentially aligned in the HAV wall. These cells were supported by microvasculature initially formed by CD34+/CD31+ cells in the neoadventitia and later maintained by CD34−/CD31+ endothelial cells in the media and lumen of the HAV. Nestin+ progenitor cells differentiated into either αSMA+ or CD31+ cells and may contribute to early recellularization and self-repair of the HAV. A mesenchymal stem cell–like CD90+ progenitor cell population increased in number with duration of implantation. Our results suggest that host myogenic, endothelial, and progenitor cell repopulation of HAVs transforms these previously acellular vessels into functional multilayered living tissues that maintain blood transport and exhibit self-healing after cannulation injury, effectively rendering these vessels like the patient’s own blood vessel.
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DOI: 10.1126/scitranslmed.3001426
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