Fractionated External Beam Radiotherapy as a Suitable Preparative Regimen for Hepatocyte Transplantation After Partial Hepatectomy

Journal Article · Fri Jul 15 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2011.02.035· OSTI ID:21587604

Krause, Petra ^[1]; Wolff, Hendrik A; Rave-Frank, Margret ^[2]; Schmidberger, Heinz ^[3]; Becker, Heinz ^[1]; Hess, Clemens Friedrich ^[2]; Christiansen, Hans ^[2]; Koenig, Sarah ^[1]

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1. Department of General and Visceral Surgery, University Medical Centre Goettingen (Germany)
2. Department of Radiotherapy and Radiation Oncology, University Medical Centre Goettingen (Germany)
3. Department of Radiooncology, Mainz University, Langenbeckstr. 1, 55131 Mainz (Germany)

Purpose: Hepatocyte transplantation is strongly considered to be a promising option to correct chronic liver failure through repopulation of the diseased organ. We already reported on extensive liver repopulation by hepatocytes transplanted into rats preconditioned with 25-Gy single dose selective external beam irradiation (IR). Herein, we tested lower radiation doses and fractionated protocols, which would be applicable in clinical use. Methods and Material: Livers of dipeptidylpeptidase IV (DPPIV)-deficient rats were preconditioned with partial liver external beam single dose IR at 25 Gy, 8 Gy, or 5 Gy, or fractionated IR at 5 x 5 Gy or 5 x 2 Gy. Four days after completion of IR, a partial hepatectomy (PH) was performed to resect the untreated liver section. Subsequently, 12 million wild-type (DPPIV{sup +}) hepatocytes were transplanted via the spleen into the recipient livers. The degree of donor cell integration and liver repopulation was studied 16 weeks after transplantation by means of immunofluorescence and DPPIV-luminescence assay. Results: Donor hepatocyte integration and liver repopulation were more effective in the irradiated livers following pretreatment with the IR doses 1 x 25 Gy and 5 x 5 Gy (formation of large DPPIV-positive cell clusters) than single-dose irradiation at 8 Gy or 5 Gy (DPPIV-positive clusters noticeably smaller and less frequent). Quantitative analysis of extracted DPPIV revealed signals exceeding the control level in all transplanted animals treated with IR and PH. Compared with the standard treatment of 1 x 25 Gy, fractionation with 5 x 5 Gy was equally efficacious, the Mann-Whitney U test disclosing no statistically significant difference (p = 0.146). The lower doses of 1 x 5 Gy, 1 x 8 Gy, and 5 x 2 Gy were significantly less effective with p < 0.05. Conclusion: This study suggests that fractionated radiotherapy in combination with PH is a conceivable pretreatment approach to prime the host liver for hepatocyte transplantation, thus bringing the experimental model a step closer to clinical application.

• OSTI ID: 21587604
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 80, Issue 4; Other Information: DOI: 10.1016/j.ijrobp.2011.02.035; PII: S0360-3016(11)00336-1; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
FRACTIONATED IRRADIATION
FRACTIONATION
HEPATECTOMY
LIVER
LIVER CELLS
RADIATION DOSES
RADIOTHERAPY
RATS
SPLEEN
ANIMAL CELLS
ANIMALS
BODY
DIGESTIVE SYSTEM
DOSES
GLANDS
IRRADIATION
MAMMALS
MEDICINE
NUCLEAR MEDICINE
ORGANS
RADIOLOGY
RODENTS
SEPARATION PROCESSES
SOMATIC CELLS
SURGERY
THERAPY
VERTEBRATES