Cellular Therapies in Pediatric Liver Diseases

Vimalesvaran, Sunitha; Nulty, Jessica; Dhawan, Anil

doi:10.3390/cells11162483

Cited by 3 publications

(6 citation statements)

References 116 publications

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“…Immunosuppression and detection of cellular rejection contributing to allogenic hepatocyte demise is a further challenge 122,124 . Alginate encapsulation of hepatocytes, facilitating a semipermeable barrier to transplanted cells, may be a promising method to avoid immune activation and rejection 121,125 …”

Section: Future Directionsmentioning

confidence: 99%

“…However, the vast majority of children with metabolic liver disease have required liver transplantation within months of this approach. 121 In some settings, this could be useful in children with severe defects as a bridge to OLT in the future. Hepatocytes have low proliferative capabilities in vitro, and despite experimental pre-conditioning approaches to enhance liver proliferation, including radiation, partial hepatic resection and portal vein embolization; effects are often short-lived.…”

Section: Hepatocyte Transplantationmentioning

confidence: 99%

“…Induced pluripotent stem cells (iPSCs), mature cells reprogrammed into an embryonic state, carry similar ethical concerns with additional oncogenic safety risks 127 . Mesenchymal stromal cells (MSC), a subtype of adult fibroblast‐like cells originating from bone marrow, synovial membrane, adipose, heart, cartilage, liver, Wharton jelly of umbilical cord and placenta are an increasing area of interest 121 . They too have a high proliferative capacity, exhibit anti‐fibrotic properties, immunomodulatory effects on both innate and adaptive immunity, and (incomplete) hepatocyte‐like differentiation potential 121,127 .…”

Section: Future Directionsmentioning

confidence: 99%

“…127 Mesenchymal stromal cells (MSC), a subtype of adult fibroblast-like cells originating from bone marrow, synovial membrane, adipose, heart, cartilage, liver, Wharton jelly of umbilical cord and placenta are an increasing area of interest. 121 They too have a high proliferative capacity, exhibit anti-fibrotic properties, immunomodulatory effects on both innate and adaptive immunity, and (incomplete) hepatocyte-like differentiation potential. 121,127 Clinical trials involving the use of MSC targeting a range of adult immune-mediated or fibroinflammatory diseases continue to progress.…”

Section: Hepatocyte Stem Cell Transplantation and Gene Therapiesmentioning

confidence: 99%

“…121 They too have a high proliferative capacity, exhibit anti-fibrotic properties, immunomodulatory effects on both innate and adaptive immunity, and (incomplete) hepatocyte-like differentiation potential. 121,127 Clinical trials involving the use of MSC targeting a range of adult immune-mediated or fibroinflammatory diseases continue to progress.…”

Section: Hepatocyte Stem Cell Transplantation and Gene Therapiesmentioning

confidence: 99%

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Current status and future directions of liver transplantation for metabolic liver disease in children

Eldredge,

Hardikar

2023

Pediatric Transplantation

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Orthotopic liver transplantation (OLT) in the care of children with inborn errors of metabolism (IEM) is well established and represent the second most common indication for pediatric liver transplantation in most centers worldwide, behind biliary atresia. OLT offers cure of disease when a metabolic defect is confined to the liver, but may still be transformative on a patient's quality of life reducing the chance of metabolic crises causing neurological damage in children be with extrahepatic involvement and no “functional cure.” Outcomes post‐OLT for inborn errors of metabolism are generally excellent. However, this benefit must be balanced with consideration of a composite risk of morbidity, and commitment to a lifetime of post‐transplant chronic disease management. An increasing number of transplant referrals for children with IEM has contributed to strain on graft access in many parts of the world. Pragmatic evaluation of IEM referrals is essential, particularly pertinent in cases where progression of extra‐hepatic disease is anticipated, with long‐term outcome expected to be poor. Decision to proceed with liver transplantation is highly individualized based on the child's dynamic risk‐benefit profile, their family unit, and their treating multidisciplinary team. Also to be considered is the chance of future treatments, such as gene therapies, emerging in the medium term.

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Section: Future Directionsmentioning

confidence: 99%

Section: Hepatocyte Transplantationmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Hepatocyte Stem Cell Transplantation and Gene Therapiesmentioning

confidence: 99%

Section: Hepatocyte Stem Cell Transplantation and Gene Therapiesmentioning

confidence: 99%

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Current status and future directions of liver transplantation for metabolic liver disease in children

Eldredge,

Hardikar

2023

Pediatric Transplantation

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Future Approaches and Therapeutic Modalities for Acute-on-Chronic Liver Failure

Wakil¹,

Niazi²,

Lunsford³

et al. 2023

Clinics in Liver Disease

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Therapeutic Cell Repopulation of the Liver: From Fetal Rat Cells to Synthetic Human Tissues

Shafritz

Ebrahimkhani

Oertel

2023

Cells

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Progenitor cells isolated from the fetal liver can provide a unique cell source to generate new healthy tissue mass. Almost 20 years ago, it was demonstrated that rat fetal liver cells repopulate the normal host liver environment via a mechanism akin to cell competition. Activin A, which is produced by hepatocytes, was identified as an important player during cell competition. Because of reduced activin receptor expression, highly proliferative fetal liver stem/progenitor cells are resistant to activin A and therefore exhibit a growth advantage compared to hepatocytes. As a result, transplanted fetal liver cells are capable of repopulating normal livers. Important for cell-based therapies, hepatic stem/progenitor cells containing repopulation potential can be separated from fetal hematopoietic cells using the cell surface marker δ-like 1 (Dlk-1). In livers with advanced fibrosis, fetal epithelial stem/progenitor cells differentiate into functional hepatic cells and out-compete injured endogenous hepatocytes, which cause anti-fibrotic effects. Although fetal liver cells efficiently repopulate the liver, they will likely not be used for human cell transplantation. Thus, utilizing the underlying mechanism of repopulation and developed methods to produce similar growth-advantaged cells in vitro, such as human induced pluripotent stem cells (iPSCs). This approach has great translational potential for developing novel cell-based therapies in patients with liver disease. The present review gives a brief overview of the classic cell transplantation models and various cell sources studied as donor cell candidates. The advantages of fetal liver-derived stem/progenitor cells are discussed, as well as the mechanism of liver repopulation. Moreover, this article reviews the potential of in vitro developed synthetic human fetal livers from iPSCs and their therapeutic benefits.

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Cellular Therapies in Pediatric Liver Diseases

Cited by 3 publications

References 116 publications

Current status and future directions of liver transplantation for metabolic liver disease in children

Current status and future directions of liver transplantation for metabolic liver disease in children

Future Approaches and Therapeutic Modalities for Acute-on-Chronic Liver Failure

Therapeutic Cell Repopulation of the Liver: From Fetal Rat Cells to Synthetic Human Tissues

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