RESUMEN
As the most prominent and ideal modality in female fertility preservation, ovarian tissue cryopreservation, and transplantation often confront the challenge of ischemic damage and follicular loss from avascular transplantation. To surmount this impediment, we engineered a novel platelet-derived factors-encapsulated fibrin hydrogel (PFH), a paradigmatic biomaterial. PFH encapsulates autologous platelet-derived factors, utilizing the physiological blood coagulation cascade for precise local delivery of bioactive molecules. In our study, PFH markedly bolstered the success of avascular ovarian tissue transplantation. Notably, the quantity and quality of follicles were preserved with improved neovascularization, accompanied by decreased DNA damage, increased ovulation, and superior embryonic development rates under a Low-concentration Platelet-rich plasma-derived factors encapsulated fibrin hydrogel (L-PFH) regimen. At a stabilized point of tissue engraftment, gene expression analysis mirrored normal ovarian tissue profiles, underscoring the effectiveness of L-PFH in mitigating the initial ischemic insult. This autologous blood-derived biomaterial, inspired by nature, capitalizes on the blood coagulation cascade, and combines biodegradability, biocompatibility, safety, and cost-effectiveness. The adjustable properties of this biomaterial, even in injectable form, extend its potential applications into the broader realm of personalized regenerative medicine. PFH emerges as a promising strategy to counter ischemic damage in tissue transplantation, signifying a broader therapeutic prospect. (197 words).
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Preservación de la Fertilidad , Hidrogeles , Isquemia , Neovascularización Fisiológica , Ovario , Femenino , Animales , Preservación de la Fertilidad/métodos , Neovascularización Fisiológica/efectos de los fármacos , Ovario/efectos de los fármacos , Hidrogeles/química , Isquemia/terapia , Humanos , Fibrina/química , Plasma Rico en Plaquetas/metabolismoRESUMEN
Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.
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Terapia Genética , Isquemia , Lípidos , Polímeros , Animales , Isquemia/terapia , Terapia Genética/métodos , Lípidos/química , Ratones , Polímeros/química , Nanopartículas/química , Factor de Crecimiento de Hepatocito/genética , Línea Celular , Transfección/métodos , Plásmidos/genética , Técnicas de Transferencia de Gen , Masculino , Miembro Posterior/irrigación sanguínea , Catalasa/metabolismoRESUMEN
BACKGROUND: Although femoropopliteal-specific stents have durable patency, stent thrombosis (ST) may occur, which can lead to acute limb ischaemia (ALI). AIMS: We aimed to investigate the clinical features and outcomes of ALI caused by femoropopliteal ST in patients with lower extremity artery disease. METHODS: This multicentre retrospective study included 499 patients with ALI - of whom 108 patients had ALI caused by femoropopliteal ST (ST-ALI) and 391 patients had ALI caused by other aetiologies (de novo ALI) - who underwent treatment between September 2011 and March 2023. Clinical features and outcomes were compared between the two groups. The primary outcome measure was 12-month amputation-free survival; factors associated with amputation or death were investigated using multivariate Cox proportional hazards regression analysis. RESULTS: Patients with ST-ALI were significantly more likely to exhibit conventional atherosclerotic risk factors, including diabetes mellitus (63% vs 26%) and haemodialysis (51% vs 10%) compared to patients with de novo ALI, whereas patients with de novo ALI were older (80 years vs 74 years) and more likely to have atrial fibrillation (49% vs 18%) than patients with ST-ALI. The 12-month amputation-free survival rate was significantly lower in the ST-ALI group than that in the de novo ALI group (51% vs 76%; p<0.001). Multivariate analysis revealed that ST-ALI, older age, haemodialysis, atrial fibrillation, the presence of a wound, peak C-reactive protein level, and non-ambulatory status all have an independent, positive association with death or major amputation. CONCLUSIONS: The current study revealed that patients with ST-ALI had worse clinical outcomes than those with de novo ALI, highlighting the need to maximise ST prevention.
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Amputación Quirúrgica , Arteria Femoral , Isquemia , Enfermedad Arterial Periférica , Arteria Poplítea , Stents , Trombosis , Humanos , Masculino , Anciano , Femenino , Estudios Retrospectivos , Arteria Poplítea/cirugía , Isquemia/terapia , Isquemia/mortalidad , Isquemia/etiología , Isquemia/cirugía , Arteria Femoral/cirugía , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/cirugía , Enfermedad Arterial Periférica/mortalidad , Anciano de 80 o más Años , Persona de Mediana Edad , Trombosis/etiología , Trombosis/mortalidad , Resultado del Tratamiento , Factores de Riesgo , Recuperación del Miembro , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/efectos adversos , Extremidad Inferior/irrigación sanguínea , Enfermedad Aguda , Grado de Desobstrucción VascularRESUMEN
Acute limb ischemia (ALI) due to arterial thromboembolic occlusion is a critical emergency in vascular medicine, requiring attention for rapid diagnosis and intervention, to prevent limb loss and major amputation, which is associated with patient disability in the long term. Traditionally, surgical embolectomy has been used for the treatment of ALI. Endovascular treatment of ALI traditionally involved catheter-directed thrombolysis. This option, however, poses some limitations, including an increased risk for access site and systemic bleeding complications, especially in patients with high bleeding risk. Therefore, in the last decades, several devices have been developed and tested for the mechanical endovascular treatment of ALI. Such devices involve either rotational thrombectomy or continuous thrombus aspiration. While rotational thrombectomy is limited in rather large arteries due to the risk of dissection and perforation in arteries <3 mm, continuous thrombus aspiration can be applied in smaller vessels and tortuous anatomies. In our case series we present a minimal-invasive endovascular approach for the treatment of two patients with ALI due to thrombotic occlusion of tortious and small diameter arteries. Minimal-invasive mechanical thrombectomy using the Penumbra Aspiration System emerged as a successful alternative to surgical embolectomy, enabling prompt treatment and with a short hospital stay for both patients. Our article therefore highlights the use of continuous thrombus aspiration in small diameter vessels and tortuous anatomies, which may represent a contraindication for the use of rotational thrombectomy. In addition, this technique may be applied even in patients with higher bleeding risk since additional lysis is not necessary in patients, where complete thrombus removal can be achieved by this device.
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Procedimientos Endovasculares , Trombectomía , Humanos , Trombectomía/instrumentación , Trombectomía/efectos adversos , Resultado del Tratamiento , Masculino , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/efectos adversos , Anciano , Femenino , Isquemia/diagnóstico , Isquemia/cirugía , Isquemia/terapia , Persona de Mediana Edad , Tromboembolia/etiología , Tromboembolia/diagnóstico , Enfermedad AgudaRESUMEN
Chronic arterial insufficiency of lower limbs (CAILL) is a common cardiovascular disease that affects 200 million subjects worldwide: from 4 to 12% of people aged 55-70 years and 20% - over 70 years. The cause of blood circulation disorder in this disease is usually a complex of pathological changes including abnormality of vessel walls' anatomical structure or integrity, disorder of blood rheological properties and alterations of its thrombotic potential. Thus, the therapy of patients with CAILL aiming at hemostasis and, in particular, platelets' aggregation is one of the most urgent problems of medicine. OBJECTIVE: To study the effectiveness of blue range visible radiation combined with basic therapy to improve hemostasis in patients with CAILL. MATERIAL AND METHODS: The number of male patients with CAILL equal 63 aged 43-57 years was examined. Blood flow parameters on a fixed part of femoral artery outside the occlusion area were registered based on subjective criteria, number of painless steps and ultrasound doppler flowmetry according to the Fontaine-Pokrovsky classification. The second degree of ischemia was diagnosed in 38 patients, the third degree - in 25 patients. All patients received basic pharmacotherapy. Patients were divided into 2 groups by simple randomization method: control group included 18 patients with II degree of ischemia and 12 patients with III degree of ischemia who received basic pharmacotherapy combined with photohemotherapy (PHT). A set of commonly used laboratory methods for examination of blood coagulation system was applied to assess the effectiveness of PHT. The number of apparently healthy people equal 26 was examined to evaluate normal value of hemostasiological parameters. RESULTS: Basic pharmacological treatment had a certain positive effect on studied hemostasis parameters and its thrombotic component. However, they did not differ statistically significantly from similar parameters before treatment on the 14th day after treatment. As a result of comprehensive therapy the changes in hemostasis system had identical and statistically significant in percentage terms changes compared to norm and baseline in patients' subgroups of study group with II and III degrees of ischemia. In addition, most hemostasis parameters in patients with II degree of ischemia were close to those of apparently healthy volunteers. Hemostasis parameters in patients with III degree of ischemia decreased to the levels of patients with II degree of ischemia before treatment. CONCLUSION: The use of basic pharmacological therapy with optical exposure to blood by blue light allows to correct hemostasis and its thrombotic component in patients with CAILL.
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Isquemia , Extremidad Inferior , Humanos , Masculino , Persona de Mediana Edad , Adulto , Isquemia/terapia , Extremidad Inferior/irrigación sanguínea , Plaquetas , Enfermedad CrónicaRESUMEN
Iatrogenic acute limb ischaemia (ALI) in neonates is a rare but severe event with potentially deleterious outcomes. In the neonatal intensive care unit, this risk is increased due to the high rate of catheterisation procedures. ALI management includes pharmacological and non-pharmacological interventions, but no commonly accepted clinical guidelines are available. In the present case, a peripheral catheter was erroneously placed in the left brachial artery of a term infant, causing blockage and ischaemia in the limb. The catheter was immediately removed, the affected limb was elevated and warm compresses were applied to the contralateral limb. The patient was treated with fresh frozen plasma, heparin, iloprost and topical nitroglycerin. Three nerve block procedures were also performed. At 6-8 days of age, significant improvement was observed. The patient was discharged at 17 days of age with near-complete resolution, whereas complete resolution was observed at postdischarge follow-up.
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Enfermedad Iatrogénica , Isquemia , Humanos , Recién Nacido , Isquemia/etiología , Isquemia/terapia , Cateterismo Periférico/efectos adversos , Arteria Braquial/diagnóstico por imagen , Heparina/administración & dosificación , Heparina/uso terapéutico , Masculino , Nitroglicerina/administración & dosificación , Nitroglicerina/uso terapéutico , Femenino , Vasodilatadores/uso terapéutico , Vasodilatadores/administración & dosificación , Iloprost/administración & dosificación , Iloprost/uso terapéutico , Enfermedad Aguda , Bloqueo Nervioso/métodosRESUMEN
Introduction: The immunomodulatory properties of mesenchymal stromal cells (MSC) have been well-characterized in in-vitro and in-vivo models. We have previously shown that liver MSC (L-MSC) are superior inhibitors of T-cell activation/proliferation, NK cell cytolytic function, and macrophage activation compared to adipose (A-MSC) and bone marrow MSC (BM-MSC) in-vitro. Method: To test these observations in-vivo, we infused these types of MSC into mice with unilateral renal artery stenosis (RAS), an established model of kidney inflammation. Unilateral RAS was induced via laparotomy in 11-week-old, male 129-S1 mice under general anesthesia. Control mice had sham operations. Human L-MSC, AMSC, and BM-MSC (5x105 cells each) or PBS vehicle were injected intra-arterially 2 weeks after surgery. Kidney morphology was studied 2 weeks after infusion using micro-MRI imaging. Renal inflammation, apoptosis, fibrosis, and MSC retention were studied ex-vivo utilizing western blot, immunofluorescence, and immunohistological analyses. Results: The stenotic kidney volume was smaller in all RAS mice, confirming significant injury, and was improved by infusion of all MSC types. All MSC-infused groups had lower levels of plasma renin and proteinuria compared to untreated RAS. Serum creatinine improved in micetreated with BM- and L-MSC. All types of MSC located to and were retained within the stenotic kidneys, but L-MSC retention was significantly higher than A- and BM-MSC. While all groups of MSC-treated mice displayed reduced overall inflammation and macrophage counts, L-MSC showed superior potency in-vivo at localizing to the site of inflammation and inducing M2 (reparative) macrophage polarization to reduce inflammatory changes. Discussion: These in-vivo findings extend our in-vitro studies and suggest that L-MSC possess unique anti-inflammatory properties that may play a role in liver-induced tolerance and lend further support to their use as therapeutic agents for diseases with underlying inflammatory pathophysiology.
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Isquemia , Hígado , Macrófagos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Ratones , Trasplante de Células Madre Mesenquimatosas/métodos , Masculino , Humanos , Hígado/patología , Hígado/inmunología , Isquemia/terapia , Isquemia/inmunología , Macrófagos/inmunología , Modelos Animales de Enfermedad , Inflamación/inmunología , Inflamación/terapia , Activación de Macrófagos , Obstrucción de la Arteria Renal/terapia , Obstrucción de la Arteria Renal/inmunología , Riñón/patología , Riñón/inmunologíaRESUMEN
Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was "switched-on" by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis.
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Isquemia , Espermatozoides , Trombosis , Animales , Masculino , Ratones , Isquemia/terapia , Espermatozoides/efectos de los fármacos , Trombosis/tratamiento farmacológico , Terapia Trombolítica/métodos , Hipertermia Inducida/métodos , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Fibrinolíticos/química , Humanos , Ratones Endogámicos C57BLRESUMEN
Critical limb ischemia is an important clinical entity due to its association with increased morbidity and mortality. The mortality and amputation-free survival remains poor especially in those where revascularization is not an option. Recently, the role of cellular therapy has emerged as a promising therapeutic measure that may aid in wound healing and revascularization and improve functional outcomes.
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Isquemia , Cicatrización de Heridas , Humanos , Cicatrización de Heridas/fisiología , Isquemia/terapia , Trasplante de Células Madre/métodos , Resultado del TratamientoRESUMEN
The rate of vascular recanalizations in CLTI is increasing worldwide. Safety and efficacy of surgical versus endovascular treatment in CLTI patients was investigated in 2 prospective randomized trials with contrasting results. The BEST-CLI trial randomized 1830 patients with CLTI, the Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL-2) trial included 345 patients with CLTI. Best-CLI evaluated outcome events as the primary endpoint, which includes major reinterventions in addition to major amputations and death. Only half of the CLTI patients received a crural intervention or surgery. There were no differences in major amputations or death. After a median follow-up (FU) of 2,7 years, the surgery group showed significantly better results compared to the endovascular group, due to fewer re-interventions. BASIL-2 used amputation-free survival as the primary outcome and only included patients with lower leg lesions. After a median FU of 40 months, endovascular therapy was found to be superior. The extremely high mortality rate was remarkable in both studies. The BEST-CLI study represents CLTI patients only to a limited degree, whereas the BASIL-2 study presents the treatment of CLTI patients with below-the-knee-lesions quite well. Both studies confirm that patients with CLTI should be treated in specialized centers that offer both crural surgery and endovascular therapy. Cardiovascular risk factor management must play a more important role in reducing the high mortality associated with CLTI.
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Amputación Quirúrgica , Humanos , Isquemia Crónica que Amenaza las Extremidades/cirugía , Isquemia Crónica que Amenaza las Extremidades/terapia , Isquemia/terapia , Procedimientos Endovasculares/métodos , Masculino , Resultado del Tratamiento , Anciano , Femenino , Persona de Mediana EdadRESUMEN
Chronic limb threatening ischemia (CLTI) poses a significant treatment challenge for vascular surgeons, interventionalists, podiatrists, and associated medical specialists. The evidence for what constitutes appropriate care is rapidly evolving and new treatment options are in constant development. This review examines the current guidelines for CLTI care, as well as reported outcomes for multiple care strategies in this patient population, including revascularization and medical optimization. We performed a literature review of the PubMed database, reviewing articles that reported outcomes for CLTI care between 2000 and 2023, and described these outcomes as they relate to the current state of CLTI treatment. Significant data are still forthcoming regarding CLTI care, but widespread adoption of appropriate CLTI care is essential for the treatment of this vulnerable population.
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Isquemia Crónica que Amenaza las Extremidades , Humanos , Resultado del Tratamiento , Factores de Riesgo , Isquemia Crónica que Amenaza las Extremidades/terapia , Procedimientos Quirúrgicos Vasculares/normas , Procedimientos Quirúrgicos Vasculares/efectos adversos , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/normas , Medicina Basada en la Evidencia/normas , Guías de Práctica Clínica como Asunto , Isquemia/terapia , Isquemia/diagnóstico , Isquemia/fisiopatología , Recuperación del Miembro , Enfermedad CrónicaRESUMEN
OBJECTIVE: This study focuses on dose-response investigation using a codon-optimized and de novo-synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug enabling of subsequent clinical studies. BACKGROUND: Gene therapy is a potential solution for patients suffering from chronic limb-threatening ischemia. Understanding the dose for effective gene delivery is crucial for future Investigational New Drug-enabling studies. METHODS: Expression of the codon-optimized E-Selectin gene was assessed by flow cytometry following in vitro cell transfection assay and RT-qPCR for murine limbs injected in vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose-response studies involved 3 cohorts of FVB/NJ mice (n=6/group) with escalating log doses of E-Selectin/AAV2 injected intramuscularly in divided aliquots, ranging from 2 × 10 9 VG to 2 × 10 11 VG, into ischemic limbs created by left femoral artery/vein ligation/excision and administration of nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent of gangrene free limb, functional limb recovery, and therapeutic angiogenesis were assessed. RESULTS: Codon-optimized E-Sel/AAV2 gene therapy exhibits a superior expression level than WT E-Sel/AAV2 gene therapy both in vitro and in vivo. Mice treated with a high dose (2 × 10 11 VG) of E-Sel/AAV2 showed significantly improved perfusion indices, lower Faber scores, increased running stamina, and neovascularization compared with lower doses tested with control groups, indicating a distinct dose-dependent response. No toxicity was detected in any of the animal groups studied. CONCLUSIONS: E-Sel/AAV2 Vascular Regeneration Gene Therapy holds promise for enhancing the recovery of ischemic hindlimb perfusion and function, with the effective dose identified in this study as 2 × 10 11 VG aliquots injected intramuscularly.
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Codón , Selectina E , Terapia Genética , Miembro Posterior , Isquemia , Animales , Terapia Genética/métodos , Ratones , Isquemia/terapia , Miembro Posterior/irrigación sanguínea , Dependovirus/genética , Vectores Genéticos , Modelos Animales de Enfermedad , Neovascularización Fisiológica , Masculino , RegeneraciónRESUMEN
Ischemic osteonecrosis, particularly glucocorticoid-induced osteonecrosis of the femoral head (GIONFH), is primarily due to the dysfunction of osteogenesis and angiogenesis. miRNA, as a therapeutic system with immense potential, plays a vital role in the treatment of various diseases. However, due to the unique microenvironmental structure of bone tissue, especially in the case of GIONFH, where there is a deficiency in the vascular system, it is challenging to effectively target and deliver to the ischemic osteonecrosis area. A drug delivery system assisted by genetically engineered cell membranes holds promise in addressing the challenge of targeted miRNA delivery. Herein, we leverage the potential of miR-21 in modulating osteogenesis and angiogenesis to design an innovative biomimetic nanoplatform system. First, we employed metal-organic frameworks (MOFs) as the core structure to load miR-21-m (miR-21-m@MOF). The nanoparticles were further coated with the membrane of bone marrow mesenchymal stem cells overexpressing CXCR4 (CM-miR-21-m@MOF), enhancing their ability to target ischemic bone areas via the CXCR4-SDF1 axis. These biomimetic nanocomposites possess both bone-targeting and ischemia-guiding capabilities, actively targeting GIONFH lesions to release miR-21-m into target cells, thereby silencing PTEN gene and activating the PI3K-AKT signaling pathway to regulate osteogenesis and angiogenesis. This innovative miRNA delivery system provides a promising therapeutic avenue for GIONFH and potentially other related ischemic bone diseases. STATEMENT OF SIGNIFICANCE.
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Membrana Celular , Estructuras Metalorgánicas , MicroARNs , Nanopartículas , Osteonecrosis , Estructuras Metalorgánicas/química , Animales , Osteonecrosis/patología , Osteonecrosis/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Membrana Celular/metabolismo , Nanopartículas/química , Osteogénesis/efectos de los fármacos , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Células Madre Mesenquimatosas/metabolismo , Ingeniería Genética , Isquemia/patología , Isquemia/terapia , Isquemia/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , ConejosRESUMEN
Aim: This study aims to investigate the effects of large extracellular vesicles (EVs) induced by pluripotent stem cell-derived mesenchymal stem cells on lower limb ischemic disease and explore its potential mechanisms. Materials & methods: The pathology of muscles was accessed by H&E staining and immunofluorescence staining. In vitro, we conducted wound-healing assay, tube formation assay, RT qPCR, ELISA, RNA sequencing and proteomic analysis. Results: iMSCs-lEVs alleviated the injury of ischemic lower limb and promoted the recovery of lower limb function. In vitro, iMSCs-lEVs promoted the proliferation, migration, and angiogenesis of HMEC-1 cells by regulating the ERK/MAPK signing pathway. Conclusion: This study demonstrated that iMSCs-lEVs promoted endothelial cell angiogenesis via the ERK/MAPK signaling pathway, thereby improving function after lower limb ischemic injury.
[Box: see text].
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Vesículas Extracelulares , Células Madre Pluripotentes Inducidas , Isquemia , Sistema de Señalización de MAP Quinasas , Neovascularización Fisiológica , Vesículas Extracelulares/metabolismo , Animales , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Isquemia/terapia , Isquemia/metabolismo , Isquemia/patología , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Ratones , Proliferación Celular , Extremidad Inferior/irrigación sanguínea , Movimiento Celular , Masculino , AngiogénesisRESUMEN
Acute limb ischaemia (ALI) is an emergent clinical condition that strains pre-hospital resources and impacts healthcare costs and patient quality of life. Hypothermia has long been used in clinical and research settings to mitigate ischaemic damage in tissues, but prompt reperfusion is needed to prevent loss of limb or function from ALI. To address the unmet need for pre-hospital intervention of threatened limbs awaiting definitive specialty care, we have focused on controlled application of hypothermia. Over years of animal experiments, phantom limb creation, and materials selection, we conceptualised and created a portable limb-cooling device that can be used alone or combined with a traditional tourniquet or resuscitative endovascular balloon occlusion of the aorta. Here, we describe our process of building and testing the device, from computer simulation through animal-limb metabolic studies, to prototype testing.
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Extremidades , Hipotermia Inducida , Isquemia , Hipotermia Inducida/métodos , Extremidades/irrigación sanguínea , Animales , Isquemia/terapia , Humanos , Enfermedad AgudaRESUMEN
Critical Limb Ischemia or chronic limb-threatening ischemia represents the end stage of peripheral artery disease where arterial flow is compromised to the lower extremities and risk of limb loss may become imminent. Revascularization of lower extremities is one of the cornerstones of limb salvage and amputation prevention. Establishing centers of high quality CLI therapy requires creating different foundational pillars in order to be successful. This article discusses critical limb ischemia center creation from the perspective of critical limb ischemia therapists working in an outpatient setting.
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Isquemia , Recuperación del Miembro , Enfermedad Arterial Periférica , Humanos , Isquemia/terapia , Isquemia/fisiopatología , Isquemia/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Crítica , Atención Ambulatoria , Isquemia Crónica que Amenaza las Extremidades/cirugía , Instituciones de Atención Ambulatoria , Resultado del Tratamiento , Grupo de Atención al Paciente , Extremidad Inferior/irrigación sanguínea , Prestación Integrada de Atención de SaludRESUMEN
Atrial fibrillation (AF) is associated with an increased risk of thromboembolic events; however, many patients with AF are noncompliant with medication regimens, which increases said risk substantially. Suboptimal health literacy presents significant hurdles to compliance with medical treatment. Here we present a case of an elderly Hispanic woman with AF and several comorbidities, including a history of dementia, who presented with consecutive recurrence of acute limb ischemia in the bilateral lower extremities just 3 days apart. Both events were successfully treated with endovascular thrombectomy. This case study not only showcases the efficacy of the latest endovascular technologies, but also draws attention to the importance of strict patient medication adherence in AF and the effects that health literacy can have on said adherence.
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Procedimientos Endovasculares , Isquemia , Trombectomía , Humanos , Trombectomía/métodos , Femenino , Isquemia/cirugía , Isquemia/terapia , Procedimientos Endovasculares/métodos , Extremidad Inferior/irrigación sanguínea , Fibrilación Atrial/cirugía , Anciano , RecurrenciaAsunto(s)
Angioplastia de Balón , Isquemia , Humanos , Isquemia/terapia , Isquemia/diagnóstico por imagen , Angioplastia de Balón/métodos , Isquemia Crónica que Amenaza las Extremidades/terapia , Isquemia Crónica que Amenaza las Extremidades/diagnóstico por imagen , Materiales Biocompatibles Revestidos , Enfermedad CrónicaRESUMEN
BACKGROUND: Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization. However, the variability seen in several factors such as cell combinations or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal "cellular-cocktail" prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties. Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination of endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT), compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI. METHODS: Balb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemic mice (after femoral ligation) that received 50 µl of physiological serum alone or a cellular combination of AT-MSCs with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular changes in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach. RESULTS: AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group presented the slowest ischemic progression along the assay. Moreover, many proteins involved in the repairing mechanisms promoted by cell treatments were identified. CONCLUSIONS: The combination of AT-MSCs with AT-ECFCs or with CB-ECFCs promoted similar revascularization in CLTI mice, by restoring blood flow levels, together with the modulation of the inflammatory and necrotic processes, and reduction of muscle damage. The protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs-induced revascularization (immune response, vascular repair, muscle regeneration, etc.).