Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits

Sligar, Andrew D.; Howe, Gretchen; Goldman, Julia; Felli, Patricia; Karanam, Varsha; Smalling, Richard W.; Baker, Aaron

doi:10.3791/58964

Cited by 7 publications

(25 citation statements)

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“…Alternatively, animal models presenting risk factors associated with PAD, such as hyperlipidemia, hypercholesterolemia, or diabetes, have also been employed. Thus, CLI models generated in hyperlipidemic and diabetic mice generally coursed with reduced collateral formation and blood flow recovery, showing better correlation with human patients [56]. Apolipoprotein E (ApoE)-deficient mice, commonly accepted as a model of atherosclerosis [4], also show a decrease of muscle regeneration after FAL surgery [37].…”

Section: Animal Models Of CLImentioning

confidence: 99%

Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia

Beltrán-Camacho

Rojas-Torres

Durán-Ruiz

2021

IJMS

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Critical limb ischemia (CLI) constitutes the most severe form of peripheral arterial disease (PAD), it is characterized by progressive blockade of arterial vessels, commonly correlated to atherosclerosis. Currently, revascularization strategies (bypass grafting, angioplasty) remain the first option for CLI patients, although less than 45% of them are eligible for surgical intervention mainly due to associated comorbidities. Moreover, patients usually require amputation in the short-term. Angiogenic cell therapy has arisen as a promising alternative for these “no-option” patients, with many studies demonstrating the potential of stem cells to enhance revascularization by promoting vessel formation and blood flow recovery in ischemic tissues. Herein, we provide an overview of studies focused on the use of angiogenic cell therapies in CLI in the last years, from approaches testing different cell types in animal/pre-clinical models of CLI, to the clinical trials currently under evaluation. Furthermore, recent alternatives related to stem cell therapies such as the use of secretomes, exosomes, or even microRNA, will be also described.

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Section: Animal Models Of CLImentioning

confidence: 99%

Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia

Beltrán-Camacho

Rojas-Torres

Durán-Ruiz

2021

IJMS

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“…The animal model that was used in our studies was previous optimized to have prolonged recovery from ischemia and resistance to growth factor induction of revascularization. 14 In this study, FGF-2 alone did not provide enhanced revascularization as assessed by angiography or histological analysis. This finding is in contrast to multiple studies that have found enhancement of revascularization in the ischemic hindlimbs of healthy rabbits using FGF-2.…”

Section: Discussionmentioning

confidence: 48%

“…We evaluated the therapy in a rabbit model of limb ischemia recently developed by our group that includes diabetes/hyperlipidemia and exhibits therapeutic resistance to revascularization. 14 Our studies demonstrate that growth factors with S4PLs markedly improve revascularization in ischemia in this model whereas growth factor therapy alone was ineffective.…”

Section: Introductionmentioning

confidence: 65%

“…Our group has previously optimized this model and shown that it has significantly impaired revascularization compared to control rabbits and other models. 14 The rabbits were given ten injections of alginate with the treatments and recovery was tracked using angiography ( Fig. 1G, H ).…”

Section: Resultsmentioning

confidence: 99%

“…Our group has previously optimized this animal model to produce therapeutic resistance to growth factor therapies and lasting ischemia beyond similar models in healthy rabbits. 14 Our previous work has demonstrated that S4PLs in combination with growth factors can enhance revascularization in healthy and diabetic mice, healthy rats and wound healing in diabetic mice. [9][10][11][12]19 In addition, we have shown that mechanistically S4PLs enhance FGF-2 activity in endothelial cells, alter subcellular trafficking of FGF-2 including increasing uptake and recycling of the growth factor, 12 and can increase the numbers of M2 macrophages in healing wounds in diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

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Syndecan-4 Proteoliposomes Enhance Revascularization in a Rabbit Hind Limb Ischemia Model of Peripheral Ischemia

Sligar

Howe²,

Goldman³

et al. 2022

Preprint

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Regenerative therapeutics for treating peripheral arterial disease are an appealing strategy for creating more durable solutions for limb ischemia. In this work, we performed preclinical testing of an injectable formulation of syndecan-4 proteoliposomes combined with growth factors as treatment for peripheral ischemia delivered in an alginate hydrogel. We tested this therapy in an advanced model of hindlimb ischemia in rabbits with diabetes and hyperlipidemia. Our studies demonstrate enhancement in vascularity and new blood vessel growth with treatment with syndecan-4 proteoliposomes in combination with FGF-2 or FGF-2/PDGF-BB. The effects of the treatments were particularly effective in enhancing vascularity in the lower limb with a 2-4 increase in blood vessels in the treatment group in comparison to the control group. In addition, we demonstrate that the syndecan-4 proteoliposomes have stability for at least 28 days when stored at 4C to allow transport and use in the hospital environment. In addition, we performed toxicity studies in the mice and found no toxic effects even when injected at high concentration. Overall, our studies support that syndecan-4 proteoliposomes markedly enhance the therapeutic potential of growth factors in the context of disease and may be promising therapeutics for inducing vascular regeneration in peripheral ischemia.

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Syndecan-4 proteoliposomes enhance revascularization in a rabbit hind limb ischemia model of peripheral ischemia

Sligar

Howe²,

Goldman

et al. 2023

Acta Biomaterialia

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Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits

Cited by 7 publications

References 0 publications

Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia

Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia

Syndecan-4 Proteoliposomes Enhance Revascularization in a Rabbit Hind Limb Ischemia Model of Peripheral Ischemia

Syndecan-4 proteoliposomes enhance revascularization in a rabbit hind limb ischemia model of peripheral ischemia

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