Hepatocyte transplantation: Consider infusion before incision

Heath, Ryan D.; Ertem, Furkan U.; Romana, Bhupinder; Ibdah, Jamal A.; Tahan, Veysel

doi:10.5500/wjt.v7.i6.317

Cited by 4 publications

(5 citation statements)

References 57 publications

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“…For the past two decades, more than 20 patients with inherited liver-based metabolic disorders have received hepatocyte transplantation. Most of these patients showed only partial and transient improvements in metabolic function for several months and finally underwent liver transplantation [ 121 – 123 ]. Among these individuals, two patients with PFIC2 showed no obvious benefits after hepatocyte transplantation, as the existing fibrosis impaired the engraftment of the transplanted hepatocytes [ 122 ].…”

Section: Main Textmentioning

confidence: 99%

Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases

et al. 2018

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BackgroundJaundice is a common symptom of inherited or acquired liver diseases or a manifestation of diseases involving red blood cell metabolism. Recent progress has elucidated the molecular mechanisms of bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis.Main bodyThe major genetic diseases causing jaundice involve disturbances of bile flow. The insufficiency of bile salts in the intestines leads to fat malabsorption and fat-soluble vitamin deficiencies. Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. Progressive familial intrahepatic cholestasis (PFIC) is the prototype of genetic liver diseases manifesting jaundice in early childhood, progressive liver fibrosis/cirrhosis, and failure to thrive. The first three types of PFICs identified (PFIC1, PFIC2, and PFIC3) represent defects in FIC1 (ATP8B1), BSEP (ABCB11), or MDR3 (ABCB4). In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype. Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis. Other cholestatic genetic disorders may have extra-hepatic manifestations, such as developmental disorders causing ductal plate malformation (Alagille syndrome, polycystic liver/kidney diseases), mitochondrial hepatopathy, and endocrine or chromosomal disorders. The diagnosis of genetic liver diseases has evolved from direct sequencing of a single gene to panel-based next generation sequencing. Whole exome sequencing and whole genome sequencing have been actively investigated in research and clinical studies. Current treatment modalities include medical treatment (ursodeoxycholic acid, cholic acid or chenodeoxycholic acid), surgery (partial biliary diversion and liver transplantation), symptomatic treatment for pruritus, and nutritional therapy. New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway.Short conclusionUnderstanding the complex pathways of jaundice and cholestasis not only enhance insights into liver pathophysiology but also elucidate many causes of genetic liver diseases and promote the development of novel treatments.

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Section: Main Textmentioning

confidence: 99%

Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases

et al. 2018

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“…Strategies for safe cellular transplantation have become a common practice (Table 1), 7,8 and the advantages of cellular over whole organ transplantation are well described (Table 2). 9 …”

Section: Advantages and Disadvantages Of Cellular Versus Solid Organ Transplantationmentioning

confidence: 99%

“…[4][5][6] Strategies for safe cellular transplantation have become a common practice (Table 1), 7,8 and the advantages of cellular over whole organ transplantation are well described (Table 2). 9 Many consider the preparation required for cellular transplantation as a significant disadvantage, and the numerous steps of islet isolation are illustrative (Table 3). 10 Similarly, as described below, other cellular transplants will need continued basic and clinical research to achieve reproducible preparation for broad application.…”

Section: Advantag E S and Disadvantag E S Of Cellul Ar Ver Sus Solid Org An Tr An S Pl Antati Onmentioning

confidence: 99%

Challenges, highlights, and opportunities in cellular transplantation: A white paper of the current landscape

Parsons

Baquerizo

Kirchner

et al. 2021

American Journal of Transplantation

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Although cellular transplantation remains a relatively small field compared to solid organ transplantation, the prospects for advancement in basic science and clinical care remain bountiful. In this review, notable historical events and the current landscape of the field of cellular transplantation are reviewed with an emphasis on islets (allo-and xeno-), hepatocytes (including bioartificial liver), adoptive regulatory immunotherapy, and stem cells (SCs, specifically endogenous organ-specific and mesenchymal). Also, the nascent but rapidly evolving field of three-dimensional bioprinting is highlighted, including its major processing steps and latest achievements. To reach its full potential where cellular transplants are a more viable alternative than solid organ transplants, fundamental change in how the field is regulated and advanced is needed. Greater public and private investment in the development of cellular transplantation is required. Furthermore, consistent with the call of multiple national transplant societies for allo-islet transplants, the oversight of cellular transplants should mirror that of solid organ transplants and not be classified under the unsustainable, outdated model | 3227 AJT PARSONS et Al.

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“…Additionally, the cost and the risk of life‐long immunosuppression have motivated scientists to develop alternative therapies . Hepatocyte transplantation (HepTx) could be a reliable alternative and an acceptable bridge to perform OLT . HepTx has the following hampering limitations: i) Low quality of livers donated for hepatocyte isolation, ii) Rapid de‐differentiation and loss of function among hepatocytes, and iii) Lack of proliferation of hepatocytes during ex vivo culture.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 Hepatocyte transplantation (HepTx) could be a reliable alternative and an acceptable bridge to perform OLT. 4,5 HepTx has the following hampering limitations: i) Low quality of livers donated for hepatocyte isolation, ii) Rapid de-differentiation and loss of function among hepatocytes, and iii) Lack of proliferation of hepatocytes during ex vivo culture. Furthermore, progressive improvement in postoperational protocols has helped transplant surgeons to successfully transplant donated livers that were so likely to be rejected before.…”

Section: Introductionmentioning

confidence: 99%

Prenatal liver stromal cells: Favorable feeder cells for long‐term culture of hepatic progenitor cells

Feizi

Zahmatkesh

Farzaneh

et al. 2019

J of Cellular Biochemistry

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Clinical and pharmaceutical applications of primary hepatocytes (PHs) are limited due to inadequate number of donated livers and potential challenges in successful maintenance of PHs in culture. Freshly isolated hepatocytes lose their specific features and rapidly de‐differentiate in culture. Bipotent hepatoblasts, as liver precursor cells that can differentiate into both hepatocytes and cholangiocytes (Alb‐ and Ck19‐positive cells, respectively), could be used as an alternative and reliable cell source to produce enough PHs for drug discovery or possible clinical applications. In this study, growth factor‐free coculture systems of prenatal or postnatal murine liver stromal cells (pre‐LSCs or post‐LSCs, respectively) were used as feeder cells to support freshly isolated mice hepatoblasts. DLK1‐positive hepatoblasts were isolated from mouse fetuses (E14.5) and cocultured with feeder cells under adherent conditions. The hepatoblasts' bipotent features, proliferation rate, and colony formation capacity were assessed on day 5 and 7 post‐seeding. Immunoﬂuorescence staining showed that the hepatoblasts remained double positive for Alb and Ck19 on both Pre‐ and Post‐LSCs, after 5 and 7 days of coculture. Moreover, application of pre‐LSCs as feeder cells significantly increased the number of DLK1‐positive cells and their proliferation rate (ie, increased the number of Ki‐67 positive cells) on day 7, compared to Post‐LSCs group. Finally, to address our ultimate goal, which was an extension of hepatoblasts ex vivo maintenance, 3D spheres of isolated hepatoblasts were, cultured in conditioned medium (CM) derived from pre‐LSCs until day 30. It was observed that the CM derived from Pre‐LSCs could successfully prolong the maintenance of hepatic progenitor cells (HPCs) in 3D suspension culture.

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Hepatocyte transplantation: Consider infusion before incision

Cited by 4 publications

References 57 publications

Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases

Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases

Challenges, highlights, and opportunities in cellular transplantation: A white paper of the current landscape

Prenatal liver stromal cells: Favorable feeder cells for long‐term culture of hepatic progenitor cells

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