Analysis of biodistribution and engraftment into the liver of genetically modified mesenchymal stromal cells derived from adipose tissue

Giuliana di Rocco, Antonietta Gentile, Annalisa Antonini, Silvia Truffa, Giulia Piaggio, Maurizio C. Capogrossi, Gabriele Toietta

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Presently, orthotopic liver transplant is the major therapeutic option for patients affected by primary liver diseases. This procedure is characterized by major invasive surgery, scarcity of donor organs, high costs, and lifelong immunosuppressive treatment. Transplant of hepatic precursor cells represents an attractive alternative. These cells could be used either for allogeneic transplantation or for autologous transplant after ex vivo genetic modification. We used stromal cells isolated from adipose tissue (AT-SCs) as platforms for autologous cell-mediated gene therapy. AT-SCs were transduced with lentiviral vectors expressing firefly luciferase, allowing for transplanted cell tracking by bioluminescent imaging (BLI). As a complementary approach, we followed circulating human α1-antitrypsin (hAAT) levels after infusion of AT-SCs overexpressing hAAT. Cells were transplanted into syngeneic mice after CCl4-induced hepatic injury. Luciferase bioluminescence signals and serum hAAT levels were measured at different time points after transplantation and demonstrate persistence of transplanted cells for up to 2 months after administration. These data, along with immunohistochemical analysis, suggest engraftment and repopulation of injured livers by transplanted AT-SCs. Moreover, by transcriptional targeting using cellular tissue-specific regulatory sequences, we confirmed that AT-SCs differentiate towards a hepatogenic-like phenotype in vitro and in vivo. Additionally, in transplanted cells reisolated from recipient animals' livers, we detected activation of the a-fetoprotein (AFP) promoter. This promoter is normally transcriptionally silenced in adult tissues but can be reactivated during liver regeneration, suggesting commitment towards hepatogenic-like differentiation of engrafted cells in vivo. Our data support AT-SCmediated gene therapy as an innovative therapeutic option for disorders of liver metabolism.

Original languageEnglish
Pages (from-to)1997-2008
Number of pages12
JournalCell Transplantation
Volume21
Issue number9
DOIs
Publication statusPublished - 2012

Fingerprint

Mesenchymal Stromal Cells
Liver
Adipose Tissue
Tissue
Transplants
Gene therapy
Genetic Therapy
Cell Tracking
Fetal Proteins
Firefly Luciferases
Liver Regeneration
Transplantation (surgical)
Bioluminescence
Homologous Transplantation
Autografts
Immunosuppressive Agents
Stromal Cells
Luciferases
Liver Diseases
Cell Differentiation

Keywords

  • Cell biology; Gene therapy; Bioluminescent imaging; Liver; Stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Analysis of biodistribution and engraftment into the liver of genetically modified mesenchymal stromal cells derived from adipose tissue. / di Rocco, Giuliana; Gentile, Antonietta; Antonini, Annalisa; Truffa, Silvia; Piaggio, Giulia; Capogrossi, Maurizio C.; Toietta, Gabriele.

In: Cell Transplantation, Vol. 21, No. 9, 2012, p. 1997-2008.

Research output: Contribution to journalArticle

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