Current Advancements in Animal Models of Postsurgical Lymphedema: A Systematic Review

Hsu, Jerry F.; Yu, Roy P.; Stanton, Eloise; Wang, Jin; Wong, Alex K.

doi:10.1089/wound.2021.0033

Cited by 14 publications

(14 citation statements)

References 125 publications

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“…Since it is difficult to reflect the pathophysiology of secondary lymphedema in animal models because of its occurrence in the chronic state, many animal models have been established to evaluate the new therapeutic strategy for lymphedema. The rodent tail lymphedema model is commonly used to evaluate the therapeutic strategies for secondary lymphedema because this model closely mimics the progression of human lymphedema, including fibrosis, fat deposition, and the infiltration of immune cells [ 104 ]. However, it is questionable whether rodent tail lymphedema mimics the pathophysiology of lymphedema in human limbs because the tail of rodents has no lymph nodes and is anatomically and physiologically different from human limbs [ 104 , 105 ].…”

Section: Discussionmentioning

confidence: 99%

“…The rodent tail lymphedema model is commonly used to evaluate the therapeutic strategies for secondary lymphedema because this model closely mimics the progression of human lymphedema, including fibrosis, fat deposition, and the infiltration of immune cells [ 104 ]. However, it is questionable whether rodent tail lymphedema mimics the pathophysiology of lymphedema in human limbs because the tail of rodents has no lymph nodes and is anatomically and physiologically different from human limbs [ 104 , 105 ]. The mouse hindlimb lymphedema model is also used as an animal model of lymphedema.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, irradiation is often necessary to create the chronic lymphedema model. However, the dose and timing of irradiation are not standardized, and the degree of edema varies widely among studies [ 104 ]. Although animal lymphedema models such as rabbit, sheep, dog, pig, and monkey have also been used to study chronic or clinically-relevant lymphedema, the numbers of these studies are limited [ 104 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, the dose and timing of irradiation are not standardized, and the degree of edema varies widely among studies [ 104 ]. Although animal lymphedema models such as rabbit, sheep, dog, pig, and monkey have also been used to study chronic or clinically-relevant lymphedema, the numbers of these studies are limited [ 104 ]. Therefore, the establishment of a common animal model that reflects the pathophysiology of human lymphedema is necessary to develop new therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

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Emerging Anti-Inflammatory Pharmacotherapy and Cell-Based Therapy for Lymphedema

Ogino

Yokooji

Hayashida

et al. 2022

IJMS

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Secondary lymphedema is a common complication of lymph node dissection or radiation therapy for cancer treatment. Conventional therapies such as compression sleeve therapy, complete decongestive physiotherapy, and surgical therapies decrease edema; however, they are not curative because they cannot modulate the pathophysiology of lymphedema. Recent advances reveal that the activation and accumulation of CD4+ T cells are key in the development of lymphedema. Based on this pathophysiology, the efficacy of pharmacotherapy (tacrolimus, anti-IL-4/IL-13 antibody, or fingolimod) and cell-based therapy for lymphedema has been demonstrated in animal models and pilot studies. In addition, mesenchymal stem/stromal cells (MSCs) have attracted attention as candidates for cell-based lymphedema therapy because they improve symptoms and decrease edema volume in the long term with no serious adverse effects in pilot studies. Furthermore, MSC transplantation promotes functional lymphatic regeneration and improves the microenvironment in animal models. In this review, we focus on inflammatory cells involved in the pathogenesis of lymphedema and discuss the efficacy and challenges of pharmacotherapy and cell-based therapies for lymphedema.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Emerging Anti-Inflammatory Pharmacotherapy and Cell-Based Therapy for Lymphedema

Ogino

Yokooji

Hayashida

et al. 2022

IJMS

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“…However, recent animal studies, newly developed mechanisms, and the validation of new treatments have brought about a change. For example, studies on lymphedema have mostly been focusing on the therapeutic effects, such as physical therapy; however, studies on lymphangiogenesis and other methods for treating edema are being actively conducted through animal experiments [13][14][15][16][17][18].…”

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confidence: 99%

Recent Trends in Rehabilitation for Cancer Patients

Seo

2022

Ann Rehabil Med

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Surgical lymphedema models in the mice hindlimb—A systematic review and quality assessment

Bucan,

Frendø,

Ngo

et al. 2023

Microsurgery

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BackgroundLymphedema constitutes a major unsolved problem in plastic surgery. To identify novel lymphedema treatments, preclinical studies are vital. The surgical mouse lymphedema model is popular and cost‐effective; nonetheless, a synthesis and overview of the literature with evidence‐based guidelines is needed. The aim of this review was to perform a systematic review to establish best practice and support future high‐quality animal studies exploring lymphedema treatments.MethodsWe performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, searching four databases (PubMed, Embase, Web of Science, and Scopus) from inception–September 2022. The Animals in Research Reporting In Vivo Experiments 2.0 (ARRIVE 2.0) guidelines were used to evaluate reporting quality. Studies claiming to surgically induce lymphedema in the hindlimb of mice were included.ResultsThirty‐seven studies were included. Four main models were used. (1) Irradiation+surgery. (2) A variation of the surgery used by (1) + irradiation. (3) Surgery only (SPDF‐model). (4) Surgery only (PLND‐model). Remaining studies used other techniques. The most common measurement modality was the caliper. Mean quality coefficient was 0.57. Eighteen studies (49%) successfully induced sustained lymphedema. Combination of methods seemed to yield the best results, with an overrepresentation of irradiation, the removal of two lymph nodes, and the disruption of both the deep and superficial lymph vessels in the 18 studies.ConclusionSurgical mouse hindlimb lymphedema models are challenged by two related problems: (1) retaining lymphedema for an extended period, that is, establishing a (chronic) lymphedema model (2) distinguishing lymphedema from post‐operative edema.Most studies failed to induce lymphedema and used error‐prone measurements. We provide an overview of studies claiming to induce lymphedema and advocate improved research via five evidence‐based recommendations to use: (1) a proven lymphedema model; (2) sufficient follow‐up time, (3) validated measurement methods; (4) ARRIVE‐guidelines; (5) contralateral hindlimb as control.

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Current Advancements in Animal Models of Postsurgical Lymphedema: A Systematic Review

Cited by 14 publications

References 125 publications

Emerging Anti-Inflammatory Pharmacotherapy and Cell-Based Therapy for Lymphedema

Emerging Anti-Inflammatory Pharmacotherapy and Cell-Based Therapy for Lymphedema

Recent Trends in Rehabilitation for Cancer Patients

Surgical lymphedema models in the mice hindlimb—A systematic review and quality assessment

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