De Silvestro Giustina, Vicarioto Maria, Donadel Carla, Menegazzo Marinella, Marson Piero, Corsini Augusto
Blood Transfusion Service, Apheresis Unit, University Hospital of Padova, Italy.
Hepatogastroenterology. 2004 May-Jun;51(57):805-10.
BACKGROUND/AIMS: Stem cells are characterized by plasticity, namely the ability of interchanging between various tissue and organs. In this regard, many studies have demonstrated the presence of antigenic structures relevant to the hematopoietic stem cell on hepatocytes, thus suggesting that in certain conditions liver cells may derive from the hematopoietic compartment. The aim of this study has been to verify whether surgical liver resection can activate bone marrow, by mobilizing peripheral blood hematopoietic stem cells (CD34+ cells) putatively able to induce liver repopulation.
White blood cell and CD34+ cell count was determined at baseline (before surgery) and then monitored in the postoperative period in 13 patients undergoing liver resection (in most cases because of malignant, primary or secondary liver diseases) and, as a control group, in 12 patients affected with other diseases requiring abdominal surgery, but not liver resection. Moreover, to assess the basal value of circulating CD34+ cells, 50 healthy blood donors were included in the study. The CD34+ cell count has been carried out by flow cytometry, by applying conventional protocols.
Patients, as altogether considered, showed at baseline a significantly higher white blood cell count as compared to healthy controls (7.41+/-2.89 x 10(3)/microL vs. 6.00+/-1.37 x 10(3)/microL, P<0.01), as opposed to the CD34+ cell count, the results of which were significantly lower (2.8+/-1.8/microL vs. 4.1+/-1.9/microL, P<0.01). The increase of CD34+ cells was significantly higher in patients following liver resection as compared to others (+6.5+/-4.1/microL vs. +0.7+/-1.4/microL, P<0.001), whereas the variation of white blood cell count was not statistically significant (+1.87+/-3.76 x 10(3)/microL vs. + 1.51+/-2.87 x 10(3)/microL).
Our results indicate that hepatic injury caused by extensive liver resection may constitute a trigger to the mobilization of hematopoietic stem cells putatively able to differentiate into hepatocytes, thus starting the recovery process of liver. These data could open innovative views to the treatment of certain liver diseases (e.g. fulminant hepatic failure), in particular by the administration of hematopoietic growth factors, such as G-CSF or GM-CSF, after the hepatic damage, to contribute, through the activation of the hematopoietic compartment, to a more efficient liver regeneration.
背景/目的:干细胞具有可塑性,即能够在不同组织和器官之间转换。在这方面,许多研究已证实在肝细胞上存在与造血干细胞相关的抗原结构,这表明在某些情况下肝细胞可能来源于造血系统。本研究的目的是验证肝切除手术是否能通过动员外周血造血干细胞(CD34+细胞)激活骨髓,这些造血干细胞可能具有诱导肝脏再填充的能力。
对13例行肝切除手术的患者(大多数因原发性或继发性肝脏恶性疾病)在基线时(手术前)测定白细胞和CD34+细胞计数,并在术后进行监测,同时选取12例因其他疾病需行腹部手术但不进行肝切除的患者作为对照组。此外,为评估循环CD34+细胞的基础值,研究纳入了50名健康献血者。采用常规方案通过流式细胞术进行CD34+细胞计数。
总体来看,患者基线时白细胞计数显著高于健康对照组(7.41±2.89×10³/μL对6.00±1.37×10³/μL,P<0.01),而CD34+细胞计数结果则显著较低(2.8±1.8/μL对4.1±1.9/μL,P<0.01)。肝切除术后患者CD34+细胞的增加显著高于其他患者(+6.5±4.1/μL对+0.7±1.4/μL,P<0.001),而白细胞计数的变化无统计学意义(+1.87±3.76×10³/μL对+1.51±2.87×10³/μL)。
我们的结果表明,广泛肝切除引起的肝损伤可能触发造血干细胞的动员,这些造血干细胞可能分化为肝细胞,从而启动肝脏的恢复过程。这些数据可能为某些肝脏疾病(如暴发性肝衰竭)的治疗开辟新的思路,特别是在肝损伤后给予造血生长因子,如粒细胞集落刺激因子(G-CSF)或粒细胞-巨噬细胞集落刺激因子(GM-CSF),通过激活造血系统,促进更有效的肝脏再生。