Treatment of newborn G6pc -/- mice with bone marrow-derived myelomonocytes induces liver repair

Roberta Resaz, Laura Emionite, Cristina Vanni, Simonetta Astigiano, Maura Puppo, Rosa Lavieri, Daniela Segalerba, Annalisa Pezzolo, Maria Carla Bosco, Alessandra Oberto, Carola Eva, Janice Y. Chou, Luigi Varesio, Ottavia Barbieri, Alessandra Eva

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: Several studies have shown that bone marrow-derived committed myelomonocytic cells can repopulate diseased livers by fusing with host hepatocytes and can restore normal liver function. These data suggest that myelomonocyte transplantation could be a promising approach for targeted and well-tolerated cell therapy aimed at liver regeneration. We sought to determine whether bone marrow-derived myelomonocytic cells could be effective for liver reconstitution in newborn mice knock-out for glucose-6-phosphatase-α. Methods: Bone marrow-derived myelomonocytic cells obtained from adult wild type mice were transplanted in newborn knock-out mice. Tissues of control and treated mice were frozen for histochemical analysis, or paraffin-embedded and stained with hematoxylin and eosin for histological examination or analyzed by immunohistochemistry or fluorescent in situ hybridization. Results: Histological sections of livers of treated knock-out mice revealed areas of regenerating tissue consisting of hepatocytes of normal appearance and partial recovery of normal architecture as early as 1 week after myelomonocytic cells transplant. FISH analysis with X and Y chromosome paints indicated fusion between infused cells and host hepatocytes. Glucose-6-phosphatase activity was detected in treated mice with improved profiles of liver functional parameters. Conclusions: Our data indicate that bone marrow-derived myelomonocytic cell transplant may represent an effective way to achieve liver reconstitution of highly degenerated livers in newborn animals.

Original languageEnglish
Pages (from-to)1263-1271
Number of pages9
JournalJournal of Hepatology
Volume55
Issue number6
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Cell fusion
  • Glucose-6-phosphatase-α
  • Hematopoietic stem cells
  • Myelomonocytes
  • Null mice

ASJC Scopus subject areas

  • Hepatology

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