scholarly journals Mice Engrafted with Human Fetal Thymic Tissue and Hematopoietic Stem Cells Develop Pathology Resembling Chronic Graft-versus-Host Disease

2013 ◽  
Vol 19 (9) ◽  
pp. 1310-1322 ◽  
Author(s):  
Jennifer L. Lockridge ◽  
Ying Zhou ◽  
Yusof A. Becker ◽  
Shidong Ma ◽  
Shannon C. Kenney ◽  
...  
2019 ◽  
Vol 47 (5) ◽  
pp. 656-660 ◽  
Author(s):  
Sundeep Chandra ◽  
Patrizia Cristofori ◽  
Carlos Fonck ◽  
Charles A. O’Neill

A therapeutic option for monogenic disorders is gene therapy with ex vivo-transduced autologous hematopoietic stem cells (HSCs). Safety or efficacy studies of ex vivo-modified HSCs are conducted in humanized mouse models after ablation of the murine bone marrow and transfer of human CD34+ HSCs. Engrafted human CD34+ cells migrate to bone marrow and differentiate into various human hematopoietic lineages. A 12-week study was conducted in NSG™ mice to evaluate engraftment, differentiation, and safety of human CD34+ cells that were transduced ( ex vivo) with a proprietary lentiviral vector encoding a human gene (BMRN-1) or a mock (green fluorescent protein) vector. Several mice intravenously injected with naive CD34+ cells or transduced CD34+ cells had variable lymphohistiocytic inflammatory cell infiltrates and microgranulomas in the liver and lungs consistent with graft-versus-host disease (GVHD). Spleen, bone marrow, stomach, reproductive tract, but not the skin had similar inflammatory changes. Ex vivo viral transduction of CD34+ cells did not impact engraftment or predispose to xenogeneic GVHD.


2015 ◽  
Vol 25 (1) ◽  
pp. 67-75
Author(s):  
Anatoliy N. Goltsev ◽  
◽  
Tatyana G. Dubrava ◽  
Yuliya A. Gaevskaya ◽  
Elena D. Lutsenko ◽  
...  

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