Inducible expression of indoleamine 2,3-dioxygenase attenuates acute rejection of tissue-engineered lung allografts in rats.
Lung disease remains one of the principal causes of death worldwide and the incidence of pulmonary diseases is increasing. Complexity in treatments and shortage of donors leads us to develop new ways for lung disease treatment. One promising strategy is preparing engineered lung for transplantation. In this context, employing new immunosuppression strategies which suppresses immune system locally rather than systemic improves transplant survival. This tends to reduce the difficulties in transplant rejection and the systemic impact of the use of immunosuppressive drugs which causes side effects such as serious infections and malignancies. In our study examining the immunosuppressive effects of IDO expression, we produced rat lung tissues with the help of decellularized tissue, differentiating medium and rat mesenchymal stem cells. Transduction of these cells by IDO expressing lentiviruses provided inducible and local expression of this gene. To examine immunosuppressive properties of IDO expression by these tissues, we transplanted these allografts into rats and, subsequently, evaluated cytokine expression and histopathological properties. Expression of inflammatory cytokines IFNγ and TNFα were significantly downregulated in IDO expressing allograft. Moreover, acute rejection score of this experimental group was also lower comparing other two groups and mRNA levels of FOXP3, a regulatory T cell marker, upregulated in IDO expressing group. However, infiltrating lymphocyte counting did not show significant difference between groups. This study demonstrates that IDO gene transfer into engineered lung allograft tissues significantly attenuates acute allograft damage suggesting local therapy with IDO as a strategy to reduce the need for systemic immunosuppression and, thereby, its side effects.
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Ammar
A
Ebrahimi
Immunology, Asthma and Allergy Research Institute, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Gholam Ali
GA
Kardar
Ladan
L
Teimoori-Toolabi
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Iran.
LadanTeimoori
L
Toolabi
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Hossein
H
Ghanbari
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: sadrodiny@sina.tums.ac.ir.
Esmaeil
E
Sadroddiny
D000818:Animals; D002454:Cell Differentiation; D015971:Gene Expression Regulation, Enzymologic; D006084:Graft Rejection / Q000235:genetics*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D016040:Lung Transplantation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology; D023822:Tissue Engineering
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
Engineered lung; Immunosuppression; Indoleamine 2,3-dioxygenase; Lung transplantation