Treatment of the Crigler–Najjar Syndrome Type I with Hepatocyte Transplantation

Fox, Ira J.; Chowdhury, Jayanta Roy; Kaufman, Stuart S.; Goertzen, Timothy C.; Chowdhury, Namita Roy; Warkentin, Phyllis I.; Dorko, Kenneth; Sauter, Bernhard; Strom, Stephen C.

doi:10.1056/nejm199805143382004

Cited by 972 publications

(638 citation statements)

References 22 publications

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“…Hepatocyte transplantation in humans has met with varied success. An infusion of isolated hepatocytes through the portal vein equivalent to 5% of the parenchymal mass to a patient with Crigler-Najjar syndrome achieved a medium-term reduction in serum bilirubin and increased bilirubin conjugate levels in the bile [43]. Hepatocyte transplantation has also been successful in the treatment of human glycogen storage disease type 1a [44], but not in the treatment of severe ornithine transcarbamylase deficiency, where rejection of the transplanted cells was thought to be the reason for only temporary (11 days) relief [45].…”

Section: Cell Therapies Using Hepatocytesmentioning

confidence: 99%

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Alison

Islam

Lim

2008

The Journal of Pathology

198

149

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The worldwide shortage of donor livers to transplant end stage liver disease patients has prompted the search for alternative cell therapies for intractable liver diseases, such as acute liver failure, cirrhosis and hepatocellular carcinoma (HCC). Under normal circumstances the liver undergoes a low rate of hepatocyte 'wear and tear' renewal, but can mount a brisk regenerative response to the acute loss of two-thirds or more of the parenchymal mass. A body of evidence favours placement of a stem cell niche in the periportal regions, although the identity of such stem cells in rodents and man is far from clear. In animal models of liver disease, adopting strategies to provide a selective advantage for transplanted hepatocytes has proved highly effective in repopulating recipient livers, but the poor success of today's hepatocyte transplants can be attributed to the lack of a clinically applicable procedure to force a similar repopulation of the human liver. The activation of bipotential hepatic progenitor cells (HPCs) is clearly vital for survival in many cases of acute liver failure, and the signals that promote such reactions are being elucidated. Bone marrow cells (BMCs) make, at best, a trivial contribution to hepatocyte replacement after damage, but other BMCs contribute to the hepatic collagen-producing cell population, resulting in fibrotic disease; paradoxically, BMC transplantation may help alleviate established fibrotic disease. HCC may have its origins in either hepatocytes or HPCs, and HCCs, like other solid tumours appear to be sustained by a minority population of cancer stem cells.

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Section: Cell Therapies Using Hepatocytesmentioning

confidence: 99%

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Alison

Islam

Lim

2008

The Journal of Pathology

198

149

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“…In a landmark study, Fox et al showed long-term metabolic benefit in a 10-year-old girl with type I Crigler-Najjar, who received 7.5 billion allogeneic hepatocytes (about 5% of the patient hepatocyte mass). 69 Transplanted cells restored bilirubin UDP-glucuronosyltransferase activity to 5.5% of control, which was sufficient to reduce total bilirubin serum levels to approximately half of the starting value and to decrease by as much the need for daily phototherapy. The appearance of conjugated bilirubin in bile demonstrated that donor hepatocytes had engrafted in the patient liver, and were still functioning for more than 2 years after cell transplantation.…”

Section: Hepatocyte Transplantation In Humansmentioning

confidence: 92%

“…70 However, serum bilirubin levels still remained very high and the patient ultimately needed OLT, indicating that allogeneic hepatocyte transplantation was partly successful. 69,71 Most recently, three studies also demonstrated metabolic benefits after hepatocyte transplantation in a patient with glycogen storage disease type 1a, with severe OTC and with peroxymal biogenesis disease. 70,72,73 These studies also showed that: (i) transplantation of normal hepatocytes as few as 1% of the patient liver mass could lead to metabolic benefits; 73 (ii) hepatocyte transplantation was safe in babies, therefore raising perspectives for ex vivo gene therapy in early stages of liver diseases; 70 (iii) repeated hepatocyte infusions (fresh and/or cryopreserved hepatocytes) allowed to obtain metabolic benefits; 70,72 and (iv) hepatocyte transplantations were insufficient to fully correct the metabolic liver diseases, therefore re-emphasizing the limitations of hepatocyte transplantation, in particular the inefficient repopulation of the recipient liver by donor cells.…”

Section: Hepatocyte Transplantation In Humansmentioning

confidence: 99%

Liver gene therapy: advances and hurdles

Nguyen

Ferry

2004

Gene Ther

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“…These have included extracorporeal bioartificial liver devices8, 9, 10 and cell therapy 11, 12, 13. Along these lines, major progress has been made with the development of bioengineering models combining primary or stem cell‐derived cells by using three‐dimensional (3D) scaffolds attempting to reproduce the complexity of tissue architecture 14.…”

Section: Introductionmentioning

confidence: 99%

Liver tissue engineering: From implantable tissue to whole organ engineering

Mazza

Al‐Akkad

Rombouts

et al. 2017

Hepatology Communications

101

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The term “liver tissue engineering” summarizes one of the ultimate goals of modern biotechnology: the possibility of reproducing in total or in part the functions of the liver in order to treat acute or chronic liver disorders and, ultimately, create a fully functional organ to be transplanted or used as an extracorporeal device. All the technical approaches in the area of liver tissue engineering are based on allocating adult hepatocytes or stem cell‐derived hepatocyte‐like cells within a three‐dimensional structure able to ensure their survival and to maintain their functional phenotype. The hosting structure can be a construct in which hepatocytes are embedded in alginate and/or gelatin or are seeded in a pre‐arranged scaffold made with different types of biomaterials. According to a more advanced methodology termed three‐dimensional bioprinting, hepatocytes are mixed with a bio‐ink and the mixture is printed in different forms, such as tissue‐like layers or spheroids. In the last decade, efforts to engineer a cell microenvironment recapitulating the dynamic native extracellular matrix have become increasingly successful, leading to the hope of satisfying the clinical demand for tissue (or organ) repair and replacement within a reasonable timeframe. Indeed, the preclinical work performed in recent years has shown promising results, and the advancement in the biotechnology of bioreactors, ex vivo perfusion machines, and cell expansion systems associated with a better understanding of liver development and the extracellular matrix microenvironment will facilitate and expedite the translation to technical applications. (Hepatology Communications 2018;2:131–141)

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Treatment of the Crigler–Najjar Syndrome Type I with Hepatocyte Transplantation

Cited by 972 publications

References 22 publications

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Liver gene therapy: advances and hurdles

Liver tissue engineering: From implantable tissue to whole organ engineering

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