Humanized Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Cell-Based Therapies

Schinnerling, Katina; Rosas, Carlos; Soto, Lilian; Thomas, Ranjeny; Aguillón, Juan Carlos

doi:10.3389/fimmu.2019.00203

Cited by 57 publications

(56 citation statements)

References 279 publications

(412 reference statements)

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“…The K/BxN model exhibits persistent pain with mechanical hypersensitivity, which does not return to baseline levels during disease progression and outlasts inflammation [155]. Table 2 briefly summarizes the pathology and pain behaviors reported in RA models [134,137,[153][154][155][156][157][158][159][160][161][162][163][164][165][166][167]. CIA, collagen-induced arthritis; CAIA, collagen antibody-induced arthritis; AIA, antigen-induced arthritis; TNF-Tg, tumor necrosis factor transgene; IL-1RA-/-, interleukin-1 receptor antagonist knockout; CII, collagen type II; Ab, antibody; mBSA, methylated bovine serum albumin; GPI, glucose-6-phosphateisomerase; hTNF, human tumor necrosis factor; RA, rheumatoid arthritis; d, day; wk, week(s); Cat S, cathepsin S; FKN, fractalkine; TLR-4, toll-like receptor 4; IL-1RI, interleukin-1 receptor type I; pCREB, phospho-CREB.…”

Section: Behavioral Tests To Assess Pain In Ra Animal Modelsmentioning

confidence: 99%

Understanding the Molecular Mechanisms Underlying the Pathogenesis of Arthritis Pain Using Animal Models

Hong

Park

Kim

2020

IJMS

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Arthritis, including osteoarthritis (OA) and rheumatoid arthritis (RA), is the leading cause of years lived with disability (YLD) worldwide. Although pain is the cardinal symptom of arthritis, which is directly related to function and quality of life, the elucidation of the mechanism underlying the pathogenesis of pain in arthritis has lagged behind other areas, such as inflammation control and regulation of autoimmunity. The lack of therapeutics for optimal pain management is partially responsible for the current epidemic of opioid and narcotic abuse. Recent advances in animal experimentation and molecular biology have led to significant progress in our understanding of arthritis pain. Despite the inherent problems in the extrapolation of data gained from animal pain studies to arthritis in human patients, the critical assessment of molecular mediators and translational studies would help to define the relevance of novel therapeutic targets for the treatment of arthritis pain. This review discusses biological and molecular mechanisms underlying the pathogenesis of arthritis pain determined in animal models of OA and RA, along with the methodologies used.

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Section: Behavioral Tests To Assess Pain In Ra Animal Modelsmentioning

confidence: 99%

Understanding the Molecular Mechanisms Underlying the Pathogenesis of Arthritis Pain Using Animal Models

Hong

Park

Kim

2020

IJMS

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“…By blocking these cytokines with a decoy receptor (TACI:Fc), they found that BLyS and APRIL regulate both B and T cell function but their effects varied depending on the presence or absence of germinal center structures, with a strong immunostimulatory effect on both types of lymphocytes only in germinal center-positive synovium [ 127 ]. Similar studies providing important contributions for disease treatment, have been described in a recent review of humanized mouse models of RA [ 126 ].…”

Section: Using His Mice To Study Tolerance and Autoimmunitymentioning

confidence: 62%

“…Rheumatoid arthritis research groups have also taken advantage of HIS hu-mice to investigate disease pathogenesis, environmental cues and pre-clinical treatments [ 126 ]. Beside the study with BLT hu-mice described above in the T1D section [ 122 ], most studies have used either PBMCs or synovial tissue from RA patients as source of human cells.…”

Section: Using His Mice To Study Tolerance and Autoimmunitymentioning

confidence: 99%

The development of human immune system mice and their use to study tolerance and autoimmunity

Costa

Lang

Torres

et al. 2019

Journal of Translational Autoimmunity

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Autoimmune diseases evolve from complex interactions between the immune system and self-antigens and involve several genetic attributes, environmental triggers and diverse cell types. Research using experimental mouse models has contributed key knowledge on the mechanisms that underlie these diseases in humans, but differences between the mouse and human immune systems can and, at times, do undermine the translational significance of these findings. The use of human immune system (HIS) mice enables the utility of mouse models with greater relevance for human diseases. As the name conveys, these mice are reconstituted with mature human immune cells transferred directly from peripheral blood or via transplantation of human hematopoietic stem cells that nucleate the generation of a complex human immune system. The function of the human immune system in HIS mice has improved over the years with the stepwise development of better models. HIS mice exhibit key benefits of the murine animal model, such as small size, robust and rapid reproduction and ease of experimental manipulation. Importantly, HIS mice also provide an applicable in vivo setting that permit the investigation of the physiological and pathological functions of the human immune system and its response to novel treatments. With the gaining popularity of HIS mice in the last decade, the potential of this model has been exploited for research in basic science, infectious diseases, cancer, and autoimmunity. In this review we focus on the use of HIS mice in autoimmune studies to stimulate further development of these valuable models.

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“…Recent studies in other tissue systems have developed humanized models (e.g. decellularized animal tissues seeded with human cells or humanized animal models) [184,185], but this has not been explored as thoroughly in tendon. Advancing models of chronic tendon injuries are needed for exploring the factors that regulate tendon pathologies in human tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

Models of tendon development and injury

Theodossiou

Schiele

2019

BMC biomed eng

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Tendons link muscle to bone and transfer forces necessary for normal movement. Tendon injuries can be debilitating and their intrinsic healing potential is limited. These challenges have motivated the development of model systems to study the factors that regulate tendon formation and tendon injury. Recent advances in understanding of embryonic and postnatal tendon formation have inspired approaches that aimed to mimic key aspects of tendon development. Model systems have also been developed to explore factors that regulate tendon injury and healing. We highlight current model systems that explore developmentally inspired cellular, mechanical, and biochemical factors in tendon formation and tenogenic stem cell differentiation. Next, we discuss in vivo, in vitro, ex vivo, and computational models of tendon injury that examine how mechanical loading and biochemical factors contribute to tendon pathologies and healing. These tendon development and injury models show promise for identifying the factors guiding tendon formation and tendon pathologies, and will ultimately improve regenerative tissue engineering strategies and clinical outcomes.

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Humanized Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Cell-Based Therapies

Cited by 57 publications

References 279 publications

Understanding the Molecular Mechanisms Underlying the Pathogenesis of Arthritis Pain Using Animal Models

Understanding the Molecular Mechanisms Underlying the Pathogenesis of Arthritis Pain Using Animal Models

The development of human immune system mice and their use to study tolerance and autoimmunity

Models of tendon development and injury

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