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Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model
Published on: July 2, 2016
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Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model.
Anjie Zhen1, Valerie Rezek2, Cindy Youn2
1David Geffen School of Medicine, University of California, Los Angeles; azhen@mednet.ucla.edu.
Journal of Visualized Experiments : Jove
|July 13, 2016
Summary
Humanized BLT mice support HIV gene therapy research. Engineered stem cells successfully differentiated and showed anti-HIV activity in this model, demonstrating its potential for studying engineered immunity.
Area of Science:
- Immunology
- Hematology
- Gene Therapy
Background:
- Developing effective stem cell-based gene therapies for HIV requires a suitable animal model.
- Existing humanized mouse models, like the Bone-marrow/Liver/Thymus (BLT) mouse, allow for human immune system reconstitution and study of hematopoietic stem cell (HSC) differentiation.
- The NSG-BLT mouse model offers a platform for studying human immune cell development and function in vivo.
Purpose of the Study:
- To establish and validate the humanized non-obese diabetic (NOD)-severe combined immunodeficient (SCID)-common gamma chain knockout (cγ(-/-))-Bone-marrow/Liver/Thymus (NSG-BLT) mouse model for studying engineered immunity against HIV.
- To demonstrate the hematopoietic differentiation and anti-HIV activity of HSCs engineered with a CD4 chimeric antigen receptor (CD4CAR) lentivirus vector in the NSG-BLT model.
Main Methods:
- Construction of humanized NSG-BLT mice using HSCs transduced with a CD4CAR lentivirus vector.
- Assessment of the differentiation capacity of CD4CAR HSCs into multiple hematopoietic lineages within the NSG-BLT model.
- Evaluation of the anti-HIV activity of the genetically modified cells in vivo.
Main Results:
- The CD4CAR HSCs successfully engrafted and differentiated into various hematopoietic lineages in the NSG-BLT mice.
- The engineered cells demonstrated significant anti-HIV activity in the humanized mouse model.
- The NSG-BLT model proved effective for studying the in vivo behavior and therapeutic potential of gene-modified HSCs.
Conclusions:
- The NSG-BLT mouse model is a valuable in vivo tool for evaluating stem cell-based gene therapies targeting HIV.
- This model facilitates the study of hematopoietic differentiation and immune function of genetically modified cells, paving the way for engineered immunity against HIV.
- Experiments involving lentivirus and human tissues require strict adherence to Biosafety Level 2 (BSL2) with special precautions (BSL2+) protocols.
