Liver Cell Transplantation: Basic Investigations for Safe Application in Infants and Small Children

Meyburg, Jochen; Alexandrova, Krassimira; Barthold, Marc; Kafert-Kasting, Sabine; Schneider, Andrea; Attaran, Masoumeh; Hoerster, Friederike; Schmidt, Jan; Hoffmann, Georg F.; Ott, Michael

doi:10.3727/096368909x470775

Cited by 30 publications

(20 citation statements)

References 31 publications

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“…They concluded that catheter sizes as small as 4.2 F yield good hepatocyte viability at sufficiently high flow rates. However, hepatocyte viability decreased with flow rates above 2 mL min −1 . Portal hypertension and the risk of portal vein thrombosis is the major limitation of the intraportal route ; however, addition of heparin might decrease this risk.…”

Section: Transplantation Techniquementioning

confidence: 99%

Hepatocyte transplantation for inherited metabolic diseases of the liver

et al. 2012

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Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation.Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic.

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Section: Transplantation Techniquementioning

confidence: 99%

Hepatocyte transplantation for inherited metabolic diseases of the liver

et al. 2012

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“…In the present study, using the rheoscope to subject hepatocyte samples to shear stress, we compared the index of viability with RLC as an index for evaluating the effect of the level of shear stress and exposure time on hepatocyte damage. Meyburg et al [5] investigated the effect of shear stress within a catheter on hepatocyte damage. From in vitro tests of hepatocyte viability using different catheters (2.2-6.6 Fr) and flow rates (1-10 mL/min), the level of shear stress was estimated to range from 0.09 to 3.47 Pa.…”

Section: Discussionmentioning

confidence: 99%

“…However, the effects of shear stress and duration of exposure on cumulative damage of hepatocytes are unclear. The effect of shear stress on hepatocyte damage has been investigated in clinical applications using catheters and tubes of different diameters [5,6]; however, the relationship between the level of shear stress and hepatocyte damage under the isolation process has received little attention.…”

Section: Introductionmentioning

confidence: 99%

Proposal of a novel evaluation index for the effects of shear stress and exposure time on hepatocyte damage

Yasuda¹,

Obara

Hsu

et al. 2015

J Artif Organs

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The purpose of this study was to propose a novel evaluation index for the effects of shear stress level and exposure time on hepatocyte damage. Suspensions of rat hepatocytes (0.5 mL) were subjected to shear stress from 1.2 to 3.1 Pa for 10 min (n = 3) using a rheoscope. We counted living and dead cells in photographs taken at 1-min intervals using a digital camera attached to the microscope. Living and dead cells were distinguished using a Trypan blue exclusion test. Under each level of shear stress, at each 1-min time interval, we measured the viability [living-cell number (t)/countable cell number (t)] and the ratio of living cells [RLC: living-cell number (t)/countable cell number in the initial condition]. The effects of shear stress and exposure time on viability and RLC were assessed by multiple regression analysis. As expected, we observed an increase in the number of dead cells and little change in the number of living cells when shear stress was increased. The coefficient of determination (R (2)) to predict the effectiveness of viability and RLC indicated a low to moderate correlation. Viability correlated with shear stress and exposure time (p < 0.001); however, RLC only correlated with exposure time of shear stress (p < 0.001). In this test condition, viability was strongly related not to living-cell damage but to dead-cell damage. Therefore, we propose RLC as a novel and effective index for investigating the effect of shear stress on living hepatocytes.

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“…The figure usually proposed that 5 % of the liver mass is equivalent to 250 million cells per kg body weight is based on estimations (Fox et al 1998), and seems probably by far underestimated for small infants for who the classical doses of 200 million cells par kg body weight is probably much less than 5 % (Meyburg et al 2009a). The number of hepatocytes in the human liver was calculated to be 2.41 × 10 11 (241 billion cells), accounting for 80 % of the total liver cell mass.…”

mentioning

confidence: 99%

Treating inborn errors of liver metabolism with stem cells: current clinical development

Sokal

2014

J of Inher Metab Disea

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Advanced therapies including stem cells are currently a major biotechnological development. Adult liver stem cells can differentiate into hepatocyte like cells and be infused in the recipient’s liver to bring a missing metabolic function. These cells can be produced in large quantities in vitro. Allogeneic stem cells are required to treat genetic diseases, and this approach allows to use one single source of tissue to treat different diseases and many recipients. Mesenchymal stem cells can in addition play an immunomodulatory and anti-inflammatory role and possibly prevent the accumulation of fibrous tissue in the liver. From a regulatory point of view, stem cells are considered as medicinal products, and must undergo a pharmaceutical development that goes beyond the research and proof-of-concept phases. Here, we review the track followed from the first hepatocyte transplantation in 2000 to the next generation product issued from stem cell technology, and the start of EMA approved clinical trials to evaluate the safety and potency of liver stem cells for the treatment of inborn errors of the liver metabolism.

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Liver Cell Transplantation: Basic Investigations for Safe Application in Infants and Small Children

Cited by 30 publications

References 31 publications

Hepatocyte transplantation for inherited metabolic diseases of the liver

Hepatocyte transplantation for inherited metabolic diseases of the liver

Proposal of a novel evaluation index for the effects of shear stress and exposure time on hepatocyte damage

Treating inborn errors of liver metabolism with stem cells: current clinical development

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