Cell therapy of critical limb ischemia-problems and 					prospects

Osipova, Olesia; Saaya, Shoraan; Карпенко, А. А.; Zakian, Suren M.; Aboian, Edouard

doi:10.1024/0301-1526/a000787

Cited by 14 publications

(9 citation statements)

References 77 publications

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“…Currently, multiple growth factors and stem cells have been tried as an angiogenic promoter [ [5] , [6] , [7] ]. However, their clinical applications are limited due to their short half-life, poor stability, off-target effects, high cost and overlook the harmful microenvironment of ischemic tissue [ 8 , 9 ]. The overexpressed H 2 O 2 in ischemic muscles results in inflammatory responses and disturbs the promotion of angiogenesis by inhibiting the vascular endothelial growth factor (VEGF) expression [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia

Chen

Duan

Diao

et al. 2021

Bioactive Materials

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The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement. Zinc ions have been reported to stimulate angiogenesis, but application was limited to the toxicity concerns. We hypothesized that zinc based metal-EGCG capsule (EGCG/Zn Ps) can achieve sustained release Zn 2+ resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG. The surface morphology, zeta potential, infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured. In vitro, EGCG/Zn showed significantly antioxidant, anti-inflammatory and induced cell migration effect. In addition, EGCG/Zn Ps enabled the sustained release of zinc ions, which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor (VEGF) in vitro and in vivo. In mouse models of limb ischemia, EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues. Moreover, EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score, limb temperature and blood flow than other groups. In conclusion, EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn 2+ and EGCG, thus enabling the direct application to limb ischemia.

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Section: Introductionmentioning

confidence: 99%

ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia

Chen

Duan

Diao

et al. 2021

Bioactive Materials

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“…Recently, cell transplantation-based therapy using stem or progenitor cells from different sources into ischemic tissues emerged as a new approach to stimulate angiogenesis and/or vasculogenesis. Among the different cell populations used, endothelial progenitor cells (EPCs), mesenchymal stromal cells (MSCs), and bone marrowmononuclear cells demonstrated their benefit in preclinical studies for ischemic disease treatment [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model

Proust¹,

Ponsen²,

Rouffiac

et al. 2020

Stem Cell Res Ther

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Background: Cardiovascular diseases are the main cause of morbidity and mortality worldwide. Restoring blood supply to ischemic tissues is an essential goal for the successful treatment of these diseases. Growth factor or gene therapy efficacy remains controversial, but stem cell transplantation is emerging as an interesting approach to stimulate angiogenesis. Among the different stem cell populations, cord blood-endothelial progenitor cells (CB-EPCs) and more particularly cord blood-endothelial progenitor cell-derived endothelial colony forming cells (CB-ECFCs) have a great proliferative potential without exhibiting signs of senescence. Even if it was already described that CB-ECFCs were able to restore blood perfusion in hind-limb ischemia in an immunodeficient mouse model, until now, the immunogenic potential of allogenic CB-ECFCs remains controversial. Therefore, our objectives were to evaluate the immune tolerance potency of CB-ECFCs and their capacity to restore a functional vascular network under ischemic condition in immunocompetent mice. Methods: In vitro, the expression and secretion of immunoregulatory markers (HLA-G, IL-10, and TGF-β1) were evaluated on CB-ECFCs. Moreover, CB-ECFCs were co-cultured with activated peripheral blood mononuclear cells (PBMCs) for 6 days. PBMC proliferation was evaluated by [3H]-thymidine incorporation on the last 18 h. In vivo, CB-ECFCs were administered in the spleen and muscle of immunocompetent mice. Tissues were collected at day 14 after surgery. Finally, CB-ECFCs were injected intradermally in C57BL/6JRj mice close to ischemic macrovessel induced by thermal cauterization. Mice recovered until day 5 and were imaged, twice a week until day 30.

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“…The adaptive vascular responses of arteriogenesis and angiogenesis are compromised within the ischaemic muscle of many CLI patients and this insufficiency in microvascular remodelling is a major predictor of disease prognosis . Therapeutic strategies to stimulate microvascular remodelling also have achieved limited success, despite promising results in pre‐clinical models . Patients with CLI experience chronic ischaemic myopathy, including myofibre atrophy and dysfunction, as well as an excessive accumulation of fatty and/or fibrotic tissue, indicating sustained deficits in muscle regeneration.…”

Section: Introductionmentioning

confidence: 99%

High‐fat diet pre‐conditioning improves microvascular remodelling during regeneration of ischaemic mouse skeletal muscle

et al. 2020

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Aim Critical limb ischaemia (CLI) is characterized by inadequate angiogenesis, arteriolar remodelling and chronic myopathy, which are most severe in type 2 diabetic patients. Hypertriglyceridaemia, commonly observed in these patients, compromises macrovascular function. However, the effects of high‐fat diet‐induced increases in circulating lipids on microvascular remodelling are not established. Here, we investigated if high‐fat diet would mimic the detrimental effect of type 2 diabetes on post‐ischaemia vascular remodelling and muscle regeneration, using a mouse model of hindlimb ischaemia. Methods Male C57Bl6/J mice were fed with normal or high‐fat diets for 8 weeks prior to unilateral femoral artery ligation. Laser doppler imaging was used to assess limb perfusion recovery. Vascular recovery, inflammation, myofibre regeneration and fibrosis were assessed at 4 or 14 days post‐ligation by histology and RNA analyses. Capillary‐level haemodynamics were assessed by intravital microscopy of control and regenerating muscles 14 days post‐ligation. Results High‐fat diet increased muscle succinate dehydrogenase activity and capillary‐level oxygen supply. At 4 days post‐ligation, no diet differences were detected in muscle damage, inflammatory infiltration or capillary activation. At 14 days post‐ligation, high fat‐fed mice displayed accelerated limb blood flow recovery, elevated capillary and arteriole densities as well as greater red blood cell supply rates and capillary‐level oxygen supply. Regenerating muscles from high fat‐fed mice displayed lower interstitial fat and collagen deposition. Conclusion The muscle‐level adaptations to high‐fat diet improved multiple aspects of muscle recovery in response to ischaemia and did not recapitulate the worse outcomes seen in diabetic CLI patients.

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Cell therapy of critical limb ischemia-problems and prospects

Cited by 14 publications

References 77 publications

ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia

ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia

Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model

High‐fat diet pre‐conditioning improves microvascular remodelling during regeneration of ischaemic mouse skeletal muscle

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