A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

Brown, Matthew E.; Zhou, Ying; McIntosh, Brian E.; Norman, Ian G.; Lou, Hannah E.; Biermann, Mitch; Sullivan, Jeremy A.; Kamp, Timothy J.; Thomson, James A.; Anagnostopoulos, Petros V.; Burlingham, William J.

doi:10.1016/j.stemcr.2018.02.011

Cited by 47 publications

(70 citation statements)

References 39 publications

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“…The limited availability of said human fetal tissues creates logistical and operational constraints. Recently, a novel BLT-like humanized mouse model has been developed using non-autologous human cord blood-derived HSCs and human neonatal/pediatric thymus, which enable investigators to construct > 1000 BLT-like humanized mice using cryopreserved thymus tissues and readily available cord blood-derived HSCs [96]. Recent studies demonstrate that these BLT-like humanized mice develop human immune cells, support HIV infection and replication, and exhibit anti-HIV immune response (unpublished data from Elie Haddad, Chloé Colas, et al, at the CanCure 5th Annual General Meeting-2019, Poster Session, in Montreal, Canada).…”

Section: Bone Marrow-liver-thymus (Blt)-humanized Mouse Modelmentioning

confidence: 99%

Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies

et al. 2020

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The development of safe and effective combination antiretroviral therapies for human immunodeficiency virus (HIV) infection over the past several decades has significantly reduced HIV-associated morbidity and mortality. Additionally, antiretroviral drugs have provided an effective means of protection against HIV transmission. Despite these advances, significant limitations exist; namely, the inability to eliminate HIV reservoirs, the inability to reverse lymphoid tissues damage, and the lack of an effective vaccine for preventing HIV transmission. Evaluation of the safety and efficacy of therapeutics and vaccines for eliminating HIV reservoirs and preventing HIV transmission requires robust in vivo models. Since HIV is a human-specific pathogen, that targets hematopoietic lineage cells and lymphoid tissues, in vivo animal models for HIV-host interactions require incorporation of human hematopoietic lineage cells and lymphoid tissues. In this review, we will discuss the construction of mouse models with human lymphoid tissues and/or hematopoietic lineage cells, termed, human immune system (HIS)-humanized mice. These HIS-humanized mouse models can support the development of functional human innate and adaptive immune cells, along with primary (thymus) and secondary (spleen) lymphoid tissues. We will discuss applications of HIS-humanized mouse models in evaluating the safety and efficacy of therapeutics against HIV reservoirs and associated immunopathology, and delineate the human immune response elicited by candidate HIV vaccines. In addition to focusing on how these HIS-humanized mouse models have already furthered our understanding of HIV and contributed to HIV therapeutics development, we discuss how emerging HIS-humanized rat models could address the limitations of HIS-mouse models.

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Section: Bone Marrow-liver-thymus (Blt)-humanized Mouse Modelmentioning

confidence: 99%

Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies

et al. 2020

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“…We, and others, have begun to utilize humanized mouse models to study immunotherapy with PDXs [44,46,47]. At our institution, the Brown and Burlingham groups have developed a NeoThy humanized mouse model using non-fetal human tissue (i.e., cryopreserved neonatal thymus and umbilical cord blood HSC) that harbors functional human hematopoietic cells [49]. We have used NeoThy mice to successfully engraft multiple human PDXs and have demonstrated that they harbor functional immune cells (currently unpublished data).…”

Section: Humanized Modelsmentioning

confidence: 99%

Patient Derived Models to Study Head and Neck Cancer Radiation Response

Cosper

Abel

Lee

et al. 2020

Cancers

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Patient-derived model systems are important tools for studying novel anti-cancer therapies. Patient-derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for the study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient-derived models for radiation research, including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

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“…However, a major limitation of the BLT model is its absolute reliance on fetal tissues. Therefore, alternative approaches involving the engraftment of immunodeficient mouse strains with embryonic stem cell-derived, thymic epithelial progenitors [293], or with neonatal thymus [294], have been recently proposed.…”

Section: Human Microenvironment and Lymphocyte Educationmentioning

confidence: 99%

Humanized Mice for Live-Attenuated Vaccine Research: From Unmet Potential to New Promises

O'Connell

Douam

2020

Vaccines

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Live-attenuated vaccines (LAV) represent one of the most important medical innovations in human history. In the past three centuries, LAV have saved hundreds of millions of lives, and will continue to do so for many decades to come. Interestingly, the most successful LAVs, such as the smallpox vaccine, the measles vaccine, and the yellow fever vaccine, have been isolated and/or developed in a purely empirical manner without any understanding of the immunological mechanisms they trigger. Today, the mechanisms governing potent LAV immunogenicity and long-term induced protective immunity continue to be elusive, and therefore hamper the rational design of innovative vaccine strategies. A serious roadblock to understanding LAV-induced immunity has been the lack of suitable and cost-effective animal models that can accurately mimic human immune responses. In the last two decades, human-immune system mice (HIS mice), i.e., mice engrafted with components of the human immune system, have been instrumental in investigating the life-cycle and immune responses to multiple human-tropic pathogens. However, their use in LAV research has remained limited. Here, we discuss the strong potential of LAVs as tools to enhance our understanding of human immunity and review the past, current and future contributions of HIS mice to this endeavor.

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A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

Cited by 47 publications

References 39 publications

Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies

Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies

Patient Derived Models to Study Head and Neck Cancer Radiation Response

Humanized Mice for Live-Attenuated Vaccine Research: From Unmet Potential to New Promises

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