Hepatic irradiation augments engraftment of donor cells following hepatocyte transplantation

Yamanouchi, Kaoru; Zhou, Haoran; Roy‐Chowdhury, Namita; Macaluso, Frank; Liu, Liping; Yamamoto, Toshiyuki; Yannam, Govardhana Rao; Enke, Charles Arthur; Solberg, Timothy D.; Adelson, Anthony B.; Platt, Jeffrey L.; Fox, Ira J.; Roy‐Chowdhury, Jayanta; Guha, Chandan

doi:10.1002/hep.22573

Cited by 117 publications

(106 citation statements)

References 29 publications

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“…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). Thus, preparative HIR has been used to correct liver function in murine and rodent models of inherited metabolic diseases, such as primary hyperoxaluria (89, 97), Wilson's disease (133), and hypercholesterolemia (218).…”

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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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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“…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%

“…In children older than 2 years, single fractions of 5 Gy have been reported to be safe, particularly if delivered to a small portion of the liver. The adverse effects of even higher radiation doses can be prevented if only a portion of the liver is radiated [98]. With this procedure, hepatic irradiation should be delivered in a single fraction and confined to only a portion (ideally less than 40%) of one lobe of the liver.…”

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, these strategies appear difficult to implement clinically because of potential toxicity. Miyazaki,Yamanouchi,et al 6 Irradiation-induced apoptosis of hepatocytes and sinusoidal endothelial cells within 24 hours after HIR improved by one week (12).…”

Section: Introductionmentioning

confidence: 99%

Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells

Miyazaki

Yamanouchi

Sakai

et al. 2013

Journal of Surgical Research

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Hepatic irradiation augments engraftment of donor cells following hepatocyte transplantation

Cited by 117 publications

References 29 publications

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

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

Clinical Hepatocyte Transplantation: Practical Limits and Possible Solutions

Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells

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