Local pharmacological induction of angiogenesis: Drugs for cells and cells as drugs

Gaspar, Diana; Peixoto, Rita; Pieri, Andrea De; Striegl, Britta; Zeugolis, Dimitrios I.; Raghunath, Michael

doi:10.1016/j.addr.2019.06.002

Cited by 17 publications

(9 citation statements)

References 514 publications

(382 reference statements)

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“…Tissue engineering techniques that combine biomaterials to protect testicular tissue and nanomedicines, providing localized and sustained drug delivery have been considered [28], and privileging local controlled delivery are important in the context of cancer as molecules acting as survival factors on distant tumor sites may have deleterious consequences for the patient [29].…”

Section: Introductionmentioning

confidence: 99%

Significant Benefits of Nanoparticles Containing a Necrosis Inhibitor on Mice Testicular Tissue Autografts Outcomes

Vento

Vermeulen

Ucakar

et al. 2019

IJMS

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Fertility preservation for prepubertal boys relies exclusively on cryopreservation of immature testicular tissue (ITT) containing spermatogonia as the only cells with reproductive potential. Preclinical studies that used a nude mice model to evaluate the development of human transplanted ITT were characterized by important spermatogonial loss. We hypothesized that the encapsulation of testicular tissue in an alginate matrix supplemented with nanoparticles containing a necrosis inhibitor (NECINH-NPS) would improve tissue integrity and germ cells’ survival in grafts. We performed orthotopic autotransplantation of 1 mm³ testicular tissue fragments recovered form mice (aged 4–5 weeks). Fragments were either non-encapsulated, encapsulated in an alginate matrix, or encapsulated in an alginate matrix containing NECINH-NPs. Grafts were recovered 5- and 21-days post-transplantation. We evaluated tissue integrity (hematoxylin-eosin staining), germ cells survival (immunohistochemistry for promyelocytic leukemia zinc-finger, VASA, and protein-boule-like), apoptosis (immunohistochemistry for active-caspase 3), and lipid peroxidation (immunohistochemistry for malondialdehyde). NECINH-NPs significantly improved testicular tissue integrity and germ cells’ survival after 21 days. Oxidative stress was reduced after 5 days, regardless of nanoparticle incorporation. No effect on caspase-dependent apoptosis was observed. In conclusion, NECINH-NPs in an alginate matrix significantly improved tissue integrity and germ cells’ survival in grafts with the perspective of higher reproductive outcomes.

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Section: Introductionmentioning

confidence: 99%

Significant Benefits of Nanoparticles Containing a Necrosis Inhibitor on Mice Testicular Tissue Autografts Outcomes

Vento

Vermeulen

Ucakar

et al. 2019

IJMS

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“…Growth factors and genes have been encapsulated into microspheres and hydrogels to facilitate revascularization and ischemia relief. 4 However, the angiogenic gene or protein-based therapy is often compromised by challenges in temporal and spatial delivery of multiple growth factors with different levels. 5 Until now, only modest success has been achieved in reducing the amputation rates of CLI patients.…”

Section: Introductionmentioning

confidence: 99%

“…For the rest of the patients, therapeutic angiogenesis is the only hope of salvaging ischemic limbs via targeting and sustained delivery of various proangiogenic agents. Growth factors and genes have been encapsulated into microspheres and hydrogels to facilitate revascularization and ischemia relief . However, the angiogenic gene or protein-based therapy is often compromised by challenges in temporal and spatial delivery of multiple growth factors with different levels .…”

Section: Introductionmentioning

confidence: 99%

Macrophage Spheroids with Chronological Phenotype Shifting To Promote Therapeutic Angiogenesis in Critical Limb Ischemia

Ran

Chen

Wei

et al. 2020

ACS Appl. Bio Mater.

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Therapeutic angiogenesis becomes an essential approach to rescue ischemia and the cell-based therapy facilitates ischemia recovery via stimulation of paracrine signals or replacement of damaged cells. Macrophages participate in multiple processes of tissue repair, and the M1 and M2 phenotypes play distinct roles in the sequential stages of healing initiation, angiogenesis stabilization, and tissue maturation. In this study, macrophage spheroids (MøSs) are proposed to promote therapeutic angiogenesis in critical limb ischemia (CLI) via chronological shifting from M1 to M2 phenotypes. Uniform-sized MøSs are prepared by using electrosprayed microcapsules as the confined growth template, and fiber fragments are inoculated to achieve a local release of chrysin for macrophage phenotype manipulation. The macrophage polarization shifting is confirmed from the decreased CD86 expressions (M1 marker) from 64.7 to 31.7% and the concurrent increase in CD206 expressions (M2 marker) from 39.3 to 72.4%. Meanwhile, the tumor necrosis factor-α secretion from M1 is downregulated by around threefold, whereas the levels of interleukin-10 and transforming growth factor-β1 from M2 increase by around threefold. The incubation with conditioned media from the MøS culture could promote the proliferation and migration of endothelial cells (ECs), showing a high healing rate of EC layers. The local treatment of hind-limb ischemia leads to a full recovery from ischemic to normal limbs with a high blood perfusion rate. Histological analysis shows few muscle degeneration and fibrosis areas and high capillary densities. As far as we know, this is the first attempt to develop uniform-sized MøSs and to undergo dynamic phenotypic shifting from early M1 to later M2 for angiogenesis promotion in the CLI treatment.

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“…Endothelial progenitor cells (EPCs) therapy for ischemia has considered as a cell-based treatment and recently introduced into clinical practice (2,3). EPCs are a minor population of circulating mononuclear cells that participates in adult neovascularization in pathological and physiological processes (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…EPCs have been shown to account for up to 26% of all ECs in neovascularization (6). The contribution of EPCs in angiogenesis has also been documented in the recovery processes of various diseases, such as myocardial ischemia (7,8), limb ischemia (2,9), ischemic stroke (10,11), and wounds (12).…”

Section: Introductionmentioning

confidence: 99%

The Dual Effect of CXCR4 Antagonist AMD3100 on the Recruitment of Endogenous Endothelial Precursor Cells and Outcome of Stroke

Xia

et al. 2020

Preprint

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Background: To examine the effect of CXCR4 antagonist AMD3100 on the recruitment of endogenous endothelial precursor cells (EPC) in ischemic boundary zone (IBZ) after permanent middle cerebral artery occlusion (pMCAO) and outcome of stroke. Methods: Adult male SD rats underwent pMCAO. AMD3100 was injected once at 1 hour (an early phase) or on day 14 (a later phase) or for 7 consecutive days from day 1 to day 7(3 mg/kg/day) after pMCAO. Flow cytometry analyses were performed to detect endogenous EPCs in peripheral blood (PB). Endogenous EPCs in IBZ were identified by immunofluorescence staining. SDF-1 expression levels in IBZ were measured by real time PCR dynamically. Infarct volume and neurological outcome including neurological score and body weight loss were used to estimate the outcome of stroke. Results: AMD3100-treatment could mobilize endogenous EPCs to PB of rats after pMCAO, and continuous AMD3100-treatment mobilized more EPCs to PB than single AMD3100-treatment. Single AMD3100 treatment at 1 hour after pMCAO rather than continuous AMD3100 treatment in an early phase could recruit endogenous EPCs in IBZ and improve neurological outcome after pMCAO. Single AMD3100 administration in later phase (on day 14) could not recruit endogenous EPCs to IBZ or improve neurological outcome after pMCAO. SDF-1 relative expression in IBZ increased in an early phase from day 1 to day 3, then decreased in later phase from day 7 to day 14. Conclusions: Our findings suggested that single AMD3100 treatment in an early phase could recruit endogenous EPCs to IBZ and improve the outcome of stroke, and AMD3100 might be used for the treatment of stroke if given at proper time window.

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Local pharmacological induction of angiogenesis: Drugs for cells and cells as drugs

Cited by 17 publications

References 514 publications

Significant Benefits of Nanoparticles Containing a Necrosis Inhibitor on Mice Testicular Tissue Autografts Outcomes

Significant Benefits of Nanoparticles Containing a Necrosis Inhibitor on Mice Testicular Tissue Autografts Outcomes

Macrophage Spheroids with Chronological Phenotype Shifting To Promote Therapeutic Angiogenesis in Critical Limb Ischemia

The Dual Effect of CXCR4 Antagonist AMD3100 on the Recruitment of Endogenous Endothelial Precursor Cells and Outcome of Stroke

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