Kerr A, Rajvanshi P, Gupta S
Department of Radiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Acad Radiol. 1994 Nov;1(3):229-36. doi: 10.1016/s1076-6332(05)80720-2.
Intrasplenic transplantation deposits hepatocytes in host hepatic sinusoids with amelioration of chronic liver failure and genetic deficiency states. Because portal resistance can be altered by intrasinusoidal transplanted cells, we examined whether hepatocyte recipients would develop deleterious portal hypertension or portosystemic collaterals.
Syngeneic hepatocytes in suspension were transplanted into recipient rats by transcatheter injection into the splenic parenchyma. Subjects included recipients of 2 x 10(7) hepatocytes representing approximately 3% of the host hepatic mass, recipients of 7.5 x 10(7) hepatocytes representing approximately 12.5% of the host hepatic mass, normal control rats, and positive control rats with portal hypertension induced by partial portal vein constriction. Portal pressures were recorded with a sensitive transducer, portosystemic collaterals were demonstrated with direct splenoportography, and survival of transplanted cells was determined with an endogenous dipeptidyl peptidase IV reporter gene.
In normal rats, the portal pressure was 6.25 +/- 1.9 mm Hg with no portosystemic collaterals. By contrast, portal pressures were significantly increased in portal vein-constricted rats, 20.7 +/- 3.9 mm Hg (P < 0.001), with extensive portosystemic collaterals. In hepatocyte recipients, portal hypertension observed during transcatheter cell injection but proved transient. When animals were examined up to 16 weeks after hepatocyte transplantation, portal pressures were in the normal range (after 2 x 10(7) cells, 7.5 x 2.6 mm Hg; after 7.5 x 10(7) cells, 9.5 +/- 4.2 mm Hg, P = not significant). No portosystemic collaterals developed in hepatocyte recipients at various times up to 8 months after transplantation. Transplanted hepatocytes expressing the reporter gene were present in recipients with assimilation in host hepatic cords.
Despite injection of a massive number of cells, transcatheter hepatocyte transplantation was devoid of any significant portal vascular alterations or toxicity in recipients. These findings are consistent with assimilation of transplanted hepatocytes into host hepatic cords and will facilitate therapeutic applications in metabolic diseases or acute liver failure.
脾内移植可使肝细胞沉积于宿主肝血窦内，改善慢性肝功能衰竭和基因缺陷状态。由于窦内移植细胞可改变门静脉阻力，我们研究了肝细胞移植受体是否会发生有害的门静脉高压或门体分流。
将悬浮的同基因肝细胞通过经导管注射至脾实质内移植到受体大鼠体内。研究对象包括接受2×10⁷个肝细胞（约占宿主肝脏质量的3%）的受体、接受7.5×10⁷个肝细胞（约占宿主肝脏质量的12.5%）的受体、正常对照大鼠以及通过部分门静脉缩窄诱导门静脉高压的阳性对照大鼠。用灵敏的传感器记录门静脉压力，通过直接脾门静脉造影显示门体分流，并用内源性二肽基肽酶IV报告基因测定移植细胞的存活情况。
正常大鼠门静脉压力为6.25±1.9 mmHg，无门体分流。相比之下，门静脉缩窄大鼠的门静脉压力显著升高，为20.7±³⁹ mmHg（P<0.001），伴有广泛的门体分流。在肝细胞移植受体中，经导管细胞注射期间观察到门静脉高压，但证明是短暂的。当在肝细胞移植后长达16周对动物进行检查时，门静脉压力处于正常范围（接受2×10⁷个细胞后，为7.5±2.6 mmHg；接受7.5×10⁷个细胞后，为9.5±4.2 mmHg，P无显著性差异）。在移植后长达八个月的不同时间，肝细胞移植受体均未形成门体分流。表达报告基因的移植肝细胞存在于受体中，并融入宿主肝索。
尽管注射了大量细胞，但经导管肝细胞移植对受体没有任何明显的门静脉血管改变或毒性。这些发现与移植肝细胞融入宿主肝索一致，将有助于代谢性疾病或急性肝功能衰竭的治疗应用。
