Impact of Angiogenic Therapy in the Treatment of Critical Lower Limb Ischemia in an Animal Model

Reis, Paulo Eduardo Ocke; Carvalho, Leonardo Pinto de; Yasumura, Eduardo Gallatti; Silva, Flávia Helena da; Garcia, Bianca Cristina; Beutel, Abram; Sacramento, Chester Bittencourt; Baptista-Silva, José Carlos Costa; Campos, Rui; Takiya, Christina Maeda; Borojević, Radovan; Han, Sang Won

doi:10.1177/1538574413518119

Cited by 4 publications

(4 citation statements)

References 25 publications

(28 reference statements)

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“…Under anesthesia, mice were transplanted in their left gastrocnemius 4 h after surgery with 30 µL of PBS (n = 20 mice) or with 30 µL of 5 × 10 5 BMCs (n = 40 mice and approximately 6 per condition) or of 5 × 10 5 MSCs (n = 35 mice and approximately 6 per condition) or of 5 × 10 5 S-MSCs (n = 40 mice and approximately 6 per condition). The quantity of injected cells (5 × 10 5 ) can be considered as low in comparison with similar previously published studies [31–33]. A 30-gauge needle was used for the unique intramuscular injection.…”

Section: Methodsmentioning

confidence: 85%

In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia

et al. 2019

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Background: Cell therapy has been proposed for patients with critical limb ischemia (CLI). Autologous bone marrow derived cells (BMCs) have been mostly used, mesenchymal stem cells (MSCs) being an alternative. The aim of this study was to characterize two types of MSCs and evaluate their efficacy. Methods: MSCs were obtained from CLI-patients BMCs. Stimulated-(S-) MSCs were cultured in endothelial growth medium. Cells were characterized by the expression of cell surface markers, the relative expression of 6 genes, the secretion of 10 cytokines and the ability to form vessel-like structures. The cell proangiogenic properties was analysed in vivo, in a hindlimb ischemia model. Perfusion of lower limbs and functional tests were assessed for 28 days after cell infusion. Muscle histological analysis (neoangiogenesis, arteriogenesis and muscle repair) was performed. Results: S-MSCs can be obtained from CLI-patients BMCs. They do not express endothelial specific markers but can be distinguished from MSCs by their secretome. S-MSCs have the ability to form tube-like structures and, in vivo, to induce blood flow recovery. No amputation was observed in S-MSCs treated mice. Functional tests showed improvement in treated groups with a superiority of MSCs and S-MSCs. In muscles, CD31+ and αSMA+ labelling were the highest in S-MSCs treated mice. S-MSCs induced the highest muscle repair. Conclusions: S-MSCs exert angiogenic potential probably mediated by a paracrine mechanism. Their administration is associated with flow recovery, limb salvage and muscle repair. The secretome from S-MSCs or secretome-derived products may have a strong potential in vessel regeneration and muscle repair.

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Section: Methodsmentioning

confidence: 85%

In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia

et al. 2019

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“…In mouse models of CLI, angiogenic therapy consisting in bone marrow cells injections resulted in reduced limb necrosis and muscle impairment, enhanced gastrocnemius and quadriceps muscle mass, and blood flow regeneration, compared with untreated ischemic animals. [83][84][85] Interestingly, in a murine hindlimb ischemic model, injections of donepezil-an anti-Alzheimer drug-upregulated angiomyogenesis factors (VEGF, HIF-1α, and Akt) and reduced skeletal muscle atrophy. 86 Data in humans did not confirm the potential benefice of angiogenesis therapy in PAD, notably showing similar exercise performance and survival rates.…”

Section: -Week Programmentioning

confidence: 99%

Sarcopenia and peripheral arterial disease: a systematic review

Pizzimenti

Meyer

Charles

et al. 2020

J cachexia sarcopenia muscle

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Background Patients with lower extremity peripheral arterial disease (PAD) and sarcopenia are a population at risk requiring specific and targeted care. The aim of this review is to gather all relevant studies associating sarcopenia and PAD and to identify the underlying pathophysiological mechanisms as well as potential therapeutic strategies to improve skeletal muscle function. Methods A systematic review was carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results Data extraction allowed the evaluation of 140 publications; 87 met the inclusion criteria; of which 79 were included in the final review, reporting sufficient data for epidemiological and diagnostic criteria, mechanical analysis, and therapeutic approaches. Epidemiological analysis and diagnostic criteria were based on 18 studies following 2362 PAD patients [31.39% (SD 7.61) women], aged 72.42 (SD 2.84); sarcopenia was present in 34.63% (SD 12.86) of the patients. Mechanical and pathway analysis were based on five animal studies and 29 clinical reports, showing significantly altered muscle strength and function in 1352 PAD patients [26.49% (SD 17.32) women], aged 67.67 (SD 5.14) years; impaired muscle histology in 192 PAD patients (9.2% (SD 11.22) women), aged 64.3 (SD 0.99) years; +58.63% (SD 25.48) of oxidative stress in 69 PAD patients [16.96% (SD 8.10) women], aged 63.17 (SD 1.43) years; mitochondriopathy in 153 PAD patients [29.39% (SD 28.27) women], aged 63.50 (SD 1.83) years; +15.58% (SD 7.41) of inflammation in 900 PAD patients [40.77% (SD 3.71) women], aged 74.88 (SD 2.76) years; and altered signalling pathways in 51 PAD patients [34.45% (SD 32.23) women], aged 72.25 (SD 5.25) years. Therapeutic approaches analysis was based on seven animal studies and 21 clinical reports. In total, 884 patients followed an exercise therapy, and 18 received an angiogenesis treatment; 30.84% (SD 17.74) were women. Mean ages of patients studied were 66.85 (SD 3.96). Conclusions Sarcopenia and lower extremity PAD have musculoskeletal consequences that directly impair patients' quality of life and prognosis. Although PAD is primarily a vascular disease, all etiological factors of sarcopenia identified so far are present in PAD. Indeed, both sarcopenia and PAD are accompanied by oxidative stress, skeletal muscle mitochondrial impairments, inflammation, inhibition of specific pathways regulating muscle synthesis or protection (i.e. IGF-1, RISK, and SAFE), and activation of molecules associated with muscle degradation. To date, besides revascularization, the best therapeutic strategy includes exercise, but approaches targeting the underlying mechanisms still deserve further studies.

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“…Despite the fact that surgical revascularization for ischemia of lower limbs can avoid amputation, this treatment does not necessarily lead to an efficient limb blood supply or mobility without pain, nor to independence of the patient [1][2][3][4]. When progression of atherosclerosis is not interrupted by the used treatments, graft failure or thrombosis may require additional interventional procedures [1][2][3][4][5]. Some patients can reach the disease stage in which the local circulatory system contains arteries of small caliber, with circulation maintained by an extensive network of collateral vessels that cannot provide an adequate supply of blood to tissues.…”

mentioning

confidence: 99%

“…In this context, there is a class of patients in a pre-amputation stage with advanced CLI of the lower limbs that are not candidates for surgery. Besides poor survival rates, prognosis with respect to limb preservation in CLI patients remains also poor, particularly in no-option CLI patients, where 6-month major amputation rates have been reported to range from 10% to 40% [1][2][3][4][5].…”

mentioning

confidence: 99%