The fate of recipient‐derived hepatocytes in sex‐mismatched liver allograft following liver transplantation

İdilman, Ramazan; Erden, Esra; Kuzu, Işınsu; Ersöz, Sadık; Karayalçın, Selim

doi:10.1111/j.1399-0012.2006.00623.x

Cited by 14 publications

(18 citation statements)

References 26 publications

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“…This finding was confirmed when Ychromosome positive hepatocytes were detected in the livers of female patients who had received bone marrow transplants from male donors (36,(40)(41)(42). The results of these studies broadened the possibility of cell based therapies for the treatment of IMDs of the liver, as the bone marrow would represent a readily available source of liver progenitor cells.…”

Section: Bone Marrow Derived Hepatocytessupporting

confidence: 60%

Stem cell therapy for inherited metabolic disorders of the liver

Ellor

Shupe

Petersen

2008

Experimental Hematology

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Modern medicine has conquered an enormous spectrum of health concerns, from the neonatal to the geriatric, the chronically ill to the acutely injured. Among the unmet challenges remaining in modern medicine are inborn disorders of metabolism within the liver. Such inherited metabolic disorders (IMDs) often leave an otherwise healthy individual with a crippling imbalance. As the principal regulator of the bodies many metabolic pathways, mal-encoded hepatic enzymes can drastically disrupt homeostasis throughout the entire body. Severe phenotypes are usually detected within the first few days of life, and treatments range from palliative lifestyle modifications, to aggressive surgical procedures. While orthotopic liver transplant is the single last resort 'cure' for these conditions, research over the past few years has brought new therapeutic technologies ever closer to the clinic. Stem cells, therapeutic viral vectors, or a combination thereof are projected to be the next, best, and final cure for IMDs, which is well reflected by this generation's research initiatives.

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Section: Bone Marrow Derived Hepatocytessupporting

confidence: 60%

Stem cell therapy for inherited metabolic disorders of the liver

Ellor

Shupe

Petersen

2008

Experimental Hematology

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“…This phenomenon was first reported in an aortic allograft model over forty years ago (9, 10) and has been observed to a limited extent when looked for in liver (11–17), kidney (18, 19) and heart (20, 21) transplants in human recipients. Fan et al (22) have also recently reported that bone marrow-derived hematopoietic stem cells and progenitor cells infiltrate allogeneic and syngeneic transplants, confirming these findings.…”

Section: Introductionmentioning

confidence: 84%

Chimeric Allografts Induced by Short‐Term Treatment With Stem Cell–Mobilizing Agents Result in Long‐Term Kidney Transplant Survival Without Immunosuppression: A Study in Rats

Okabayashi

Cameron

et al. 2016

American Journal of Transplantation

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Transplant tolerance allowing the elimination of life long immunosuppression has been the goal of research for 60 years. The induction of mixed chimerism has shown promise and has been successfully extended to large animals and the clinic. However, it remains cumbersome and requires heavy early immunosuppression. Here, we report that 4 injections of AMD3100 (A), a CXCR-4 antagonist, plus 8 injections of low-dose FK506 (F, 0.05mg/kg/day) first week after kidney transplantation extended survival, but death from renal failure occurred at 30–90 days. Repeating the same course of A and F at 1, 2 and 3 months after transplant resulted in 92% allograft acceptance (n=12) at 7 months, normal kidney function and histology with no further treatment. Transplant acceptance was associated with the influx of host stem cells resulting in a hybrid kidney and a modulated host immune response. Confirmation of these results could initiate a paradigm shift in post-transplant therapy.

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“…Whereas we and others have demonstrated that there is no or very little involvement of BM-HSC in liver regeneration after OLT [17, 19, 24], other studies reported findings of donor derived hepatocytes in patients that received liver or bone marrow transplants [14–16, 22, 23]. The frequency of BM-HSC derived hepatocytes varied between percentages <1% and 8% with some authors using sampling error corrections.…”

Section: Bone Marrow Derived Hematopoietic Stem Cells As Source Fomentioning

confidence: 71%

“…Multiplication of frequency values with these correction factors lead to a reported frequency of BM-HSC derived hepatocytes of up to 43% [15]. Longitudinally performed biopsies suggest that hepatocyte chimerism is an early event (if it occurs at all) which is not correlated with the severity of injury [22, 23]. Several groups examined the status of hepatic cellular chimerism after OLT, reporting that substantial levels of chimerism are commonly found in macrophages, Kupffer cells and endothelial cells of the liver, and bile duct, whereas hepatocyte chimerism was seen only occasionally [18, 20, 21].…”

Section: Bone Marrow Derived Hematopoietic Stem Cells As Source Fomentioning

confidence: 99%

Implication for Bone Marrow Derived Stem Cells in Hepatocyte Regeneration after Orthotopic Liver Transplantation

Pilat

Unger

Berlakovich

2013

International Journal of Hepatology

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The liver has the outstanding ability to regenerate itself and restore parenchymal tissue after injury. The most common cell source in liver growth/regeneration is replication of preexisting hepatocytes although liver progenitor cells have been postulated to participate in liver regeneration in cases of massive injury. Bone marrow derived hematopoietic stem cells (BM-HSC) have the formal capacity to act as a source for hepatic regeneration under special circumstances; however, the impact of this process in liver tissue maintenance and regeneration remains controversial. Whether BM-HSC are involved in liver regeneration or not would be of particular interest as the cells have been suggested to be an alternative donor source for the treatment of liver failure. Data from murine models of liver disease show that BM-HSC can repopulate liver tissue and restore liver function; however, data obtained from human liver transplantation show only little evidence for liver regeneration by this mechanism. The cell source for liver regeneration seems to depend on the nature of regeneration process and the extent of injury; however, the precise mechanisms still need to be resolved. Current data suggest, that in human orthotopic liver transplantation, liver regeneration by BM-HSC is a rather rare event and therefore not of clinical relevance.

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The fate of recipient‐derived hepatocytes in sex‐mismatched liver allograft following liver transplantation

Abstract: Based on these results, we suggest that ''recipient-specific bone marrow-derived hepatocyte repopulation'' in liver allograft during tissue injury is a relatively early event.

Cited by 14 publications

References 26 publications

Stem cell therapy for inherited metabolic disorders of the liver

Stem cell therapy for inherited metabolic disorders of the liver

Chimeric Allografts Induced by Short‐Term Treatment With Stem Cell–Mobilizing Agents Result in Long‐Term Kidney Transplant Survival Without Immunosuppression: A Study in Rats

Implication for Bone Marrow Derived Stem Cells in Hepatocyte Regeneration after Orthotopic Liver Transplantation

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