Liver irradiation: a potential preparative regimen for hepatocyte transplantation

Guha, Chandan; Parashar, Bhupesh; Deb, N.; Sharma, Anand; Gorla, Giridhar R.; Alfieri, Alan A.; Roy‐Chowdhury, Namita; Roy‐Chowdhury, Jayanta; Bhatia, Vikram

doi:10.1016/s0360-3016(00)01495-4

Cited by 34 publications

(25 citation statements)

References 46 publications

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“…The initial sub-lethal irradiation damage of recipient mice to allow engraftment of BM may therefore have created enough damage to the liver to effect signals for bone marrow recruitment [21]. Irradiation results in hepatocyte death during mitosis and thus reduces hepatocyte proliferation in response to liver damage [22], creating the opportunity for donor cells to be recruited to assist in liver repair. Without irradiation, we found no engraftment of DL BM cells in the liver of tx mice [1], suggesting that potential liver damage from irradiation is a prior requirement for liver engraftment.…”

Section: Discussionmentioning

confidence: 99%

Correction of copper metabolism is not sustained long term in Wilson’s disease mice post bone marrow transplantation

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Correction of copper metabolism is not sustained long term in Wilson’s disease mice post bone marrow transplantation

et al. 2007

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“…Irradiation of the native liver has been investigated in preclinical models as a method to inhibit native hepatocyte proliferation, to transiently disrupt the sinusoidal endothelial barrier, and to inhibit phagocytic activity of Kupffer cells, without a systemic toxic effect as is commonly seen with endothelial disruption drugs [98,99,100]. As reported, the disruption of the physical endothelial barrier to injected hepatocytes reaches a peak value within 24 h by increasing apoptosis of endothelial cells.…”

Section: Preconditioning Treatments To Enhance Engraftment and Prolifmentioning

confidence: 99%

Clinical Hepatocyte Transplantation: Practical Limits and Possible Solutions

et al. 2015

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Since the first human hepatocyte transplants (HTx) in 1992, clinical studies have clearly established proof of principle for this therapy as a treatment for patients with acquired or inherited liver disease. Although major accomplishments have been made, there are still some specific limitations to this technology, which, if overcome, could greatly enhance the efficacy and implementation of this therapy. Here, we describe what in our view are the most significant obstacles to the clinical application of HTx and review the solutions currently proposed. The obstacles of significance include the limited number and quality of liver tissues as a cell source, the lack of clinical grade reagents, quality control evaluation of hepatocytes prior to transplantation, hypothermic storage of cells prior to transplantation, preconditioning treatments to enhance engraftment and proliferation of donor cells, tracking or monitoring cells after transplantation, and the optimal immunosuppression protocols for transplant recipients.

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“…However, HT is limited because the number of cells that can be safely transplanted into the liver is inadequate to compensate for liver function. Encouraged by the massive repopulation of donor hepatocytes after HT for ameliorating RILD in rodents, focal liver irradiation was examined as a preparative regimen for HT in the treatment of metabolic liver diseases (85)(86)(87). Several investigators have demonstrated that preparative HIR in combination with hepatic mitogenic signals can enable selective engraftment (209) and proliferation of donor hepatocytes in irradiated host livers (37, 111, 132).…”

Section: Stem Cell Therapy To Ameliorate Radiation-induced Liver Diseasementioning

confidence: 99%

Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

Benderitter

Caviggioli

Chapel

et al. 2014

Antioxidants & Redox Signaling

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Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for restoring functionality to the irradiated tissue bed. Recent Advances: Preclinical studies presented in this review provide encouraging proof of concept regarding the therapeutic potential of stem cells for treating the adverse side effects associated with radiotherapy in different organs. Early-stage clinical data for radiation-induced lung, bone, and skin complications are promising and highlight the importance of selecting the appropriate stem cell type to stimulate tissue regeneration. Critical Issues: While therapeutic efficacy has been demonstrated in a variety of animal models and human trials, a range of additional concerns regarding stem cell transplantation for ameliorating radiationinduced normal tissue sequelae remain. Safety issues regarding teratoma formation, disease progression, and genomic stability along with technical issues impacting disease targeting, immunorejection, and clinical scale-up are factors bearing on the eventual translation of stem cell therapies into routine clinical practice. Future Directions: Follow-up studies will need to identify the best possible stem cell types for the treatment of early and late radiation-induced normal tissue injury. Additional work should seek to optimize cellular dosing regimes, identify the best routes of administration, elucidate optimal transplantation windows for introducing cells into more receptive host tissues, and improve immune tolerance for longer-term engrafted cell survival into the irradiated microenvironment. Antioxid. Redox Signal. 21, 338-355.

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Liver irradiation: a potential preparative regimen for hepatocyte transplantation

Cited by 34 publications

References 46 publications

Correction of copper metabolism is not sustained long term in Wilson’s disease mice post bone marrow transplantation

Correction of copper metabolism is not sustained long term in Wilson’s disease mice post bone marrow transplantation

Clinical Hepatocyte Transplantation: Practical Limits and Possible Solutions

Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

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