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自体干细胞构建的同种异体静脉移植:概念验证研究。

Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study.

机构信息

Department of Surgery, University of Gothenburg, Sahlgrenska University Hospital, Sweden.

出版信息

Lancet. 2012 Jul 21;380(9838):230-7. doi: 10.1016/S0140-6736(12)60633-3. Epub 2012 Jun 14.

DOI:10.1016/S0140-6736(12)60633-3
PMID:22704550
Abstract

BACKGROUND

Extrahepatic portal vein obstruction can have severe health consequences. Variceal bleeding associated with this disorder causes upper gastrointestinal bleeding, leading to substantial morbidity and mortality. We report the clinical transplantation of a deceased donor iliac vein graft repopulated with recipient autologous stem cells in a patient with extrahepatic portal vein obstruction.

METHODS

A 10 year old girl with extrahepatic portal vein obstruction was admitted to the Sahlgrenska University Hospital in Gothenburg, Sweden, for a bypass procedure between the superior mesenteric vein and the intrahepatic left portal vein (meso Rex bypass). A 9 cm segment of allogeneic donor iliac vein was decellularised and subsequently recellularised with endothelial and smooth muscle cells differentiated from stem cells obtained from the bone marrow of the recipient. This graft was used because the patient's umbilical vein was not suitable and other strategies (eg, liver transplantation) require lifelong immunosuppression.

FINDINGS

The graft immediately provided the recipient with a functional blood supply (25-30 cm/s in the portal vein and 40 mL/s in the artery was measured intraoperatively and confirmed with ultrasound). The patient had normal laboratory values for 9 months. However, at 1 year the blood flow was low and, on exploration, the shunt was patent but too narrow due to mechanical obstruction of tissue in the mesocolon. Once the tissue causing the compression was removed the graft dilated. We therefore used a second stem-cell populated vein graft to lengthen the previous graft. After this second operation, the portal pressure was reduced from 20 mm Hg to 13 mm Hg and blood flow was 25-40 cm/s in the portal vein. With restored portal circulation the patient has substantially improved physical and mental function and growth. The patient has no anti-endothelial cell antibodies and is receiving no immunosuppressive drugs.

INTERPRETATION

An acellularised deceased donor vein graft recellularised with autologous stem cells can be considered for patients in need of vascular vein shunts without the need for immunosuppression.

FUNDING

Swedish Government.

摘要

背景

肝外门静脉阻塞可导致严重的健康后果。与该疾病相关的静脉曲张出血可导致上消化道出血,从而导致大量发病率和死亡率。我们报告了一例肝外门静脉阻塞患者接受同种异体髂静脉移植物移植并接受受者自体干细胞再灌注的临床移植。

方法

一名 10 岁女孩因肝外门静脉阻塞症入住瑞典哥德堡萨尔格伦斯卡大学医院,接受肠系膜上静脉与肝内左门静脉之间的旁路手术(间 Rex 旁路)。将 9 厘米的同种异体供体髂静脉去细胞化,然后用来自受者骨髓的干细胞分化的内皮和平滑肌细胞再细胞化。之所以选择这种移植物,是因为患者的脐静脉不合适,而其他策略(例如肝移植)需要终生免疫抑制。

发现

移植物立即为受者提供了功能血液供应(术中测量门静脉为 25-30cm/s,动脉为 40mL/s,并通过超声证实)。患者 9 个月的实验室值正常。然而,在 1 年时,血流较低,在探查时,分流术是开放的,但由于系膜组织的机械性阻塞而太窄。一旦去除导致压迫的组织,移植物就会扩张。因此,我们使用第二个干细胞定植的静脉移植物来延长前一个移植物。第二次手术后,门静脉压力从 20mmHg 降至 13mmHg,门静脉血流为 25-40cm/s。随着门静脉循环的恢复,患者的身体和精神功能以及生长状况得到了极大改善。患者没有抗内皮细胞抗体,也没有接受免疫抑制药物。

解释

用自体干细胞再细胞化的去细胞化已故供体静脉移植物可考虑用于需要血管静脉分流术而无需免疫抑制的患者。

资金

瑞典政府。

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