Endothelial progenitor cell secretome delivered by novel polymeric nanoparticles in ischemic hindlimb

Felice, Francesca; Piras, Anna Maria; Rocchiccioli, Silvia; Barsotti, Maria Chiara; Santoni, Tatiana; Pucci, Angela; Burchielli, Silvia; Chiellini, Emo; Ucciferri, Nadia; Solaro, Roberto; Altomare, Angelina; Cecchettini, Antonella; Stefano, Rossella Di

doi:10.1016/j.ijpharm.2018.03.015

Cited by 26 publications

(27 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The discrepant findings possibly result from the artificial conditions that were used in our investigation. Felice and colleagues [27] exposed the cells to hypoxic conditions while we subjected PACs to specific mediators that were shown to significantly increase the AKI protective activity of intact cells [8,[15][16][17]. Regarding the fact that our study failed to show any beneficial effects of the secretome at all, the data substantially indicate that renoprotective effects of whole cells most likely require the mere presence of intact PACs in the kidney, especially if preconditioning protocols are in use.…”

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

Dihazi¹,

Schwarze²,

Patschan³

et al. 2020

Preprint

View full text Add to dashboard Cite

Acute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies focused on so-called Proangiogenic Cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production / secretion of extracellular vesicles (MV -microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and / or the secretome alone. AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI -40 minutes). Syngeneic murine PACs were stimulated with either melatonine, Angiopoietin-1 or -2, or with Bone Morphogenetic Protein-5 (BMP-5) for one hour, respectively. PACderived MV and the vesicle-depleted supernatant were subsequently collected and i.v. injected postischemia. Mice were analyzed 48 hours later. IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened post-ischemic renal function even further: MV+Ang-1, MV+BMP-5, MV+melatonin, and MV+secretome+Ang-1. Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonine, BMP-5), other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.

show abstract

Section: Discussionmentioning

confidence: 68%

“…Thus, they detected mediators with substantial proangiogenic activity. The third study that needs to be mentioned focused on EPC secretome-enriched nanoparticles in vascular repair [27]. It was documented that hypoxia stimulated the production of secretome proteins with angiogenic properties.…”

Section: Discussionmentioning

confidence: 99%

PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

Dihazi¹,

Schwarze²,

Patschan³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Felice and colleagues [27] exposed the cells to hypoxic conditions while we subjected PACs to specific mediators that were shown to significantly increase the AKI protective activity of intact cells [8,[15][16][17]. Regarding the fact that our study failed to show any beneficial effects of the secretome at all, the data substantially indicate that renoprotective effects of whole cells most likely require the mere presence of intact PACs in the kidney, especially if preconditioning protocols are in use.…”

Section: Discussionmentioning

confidence: 68%

“…Thus, they detected mediators with substantial proangiogenic activity. The third study that needs to be mentioned focused on EPC secretomeenriched nanoparticles in vascular repair [27]. It was documented that hypoxia stimulated the production of secretome proteins with angiogenic properties.…”

Section: Discussionmentioning

confidence: 99%

PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

Dihazi

Schwarze

Patschan

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Acute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies focused on so-called Proangiogenic Cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production / secretion of extracellular vesicles (MV - microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and / or the secretome alone.Methods: AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI - 40 minutes). Syngeneic murine PACs were stimulated with either melatonine, Angiopoietin-1 or -2, or with Bone Morphogenetic Protein-5 (BMP-5) for one hour, respectively. PAC-derived MV and the vesicle-depleted supernatant were subsequently collected and i.v. injected post-ischemia. Mice were analyzed 48 hours later.Results: IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened post-ischemic renal function even further: MV+Ang-1, MV+BMP-5, MV+melatonin, and MV+secretome+Ang-1.Conclusion: Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonine, BMP-5), other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.

show abstract

“…These data are in line with recent reports in which the EOC secretome has been packaged in nanoparticles or hydrogels to treat acute ischemic diseases. 59,60 Previous studies determined that in the absence of the cholesterol efflux transporters (Abca1 and Abcg1) in myeloid cells of the bone marrow was insufficient to explain the anti-atherogenic effects of LXRs described in whole bone marrow transplant experiments. [9][10][11][12][13][14] Our data support the role of another effector cell (EPC) in contributing to the anti-atherogenic effects of LXR.…”

Section: Discussionmentioning

confidence: 99%

The Secretome of Liver X Receptor Agonist Treated Early Outgrowth Cells Decreases Atherosclerosis inLdlr-/- Mice

Rasheed

Shawky

Tsai

et al. 2019

Preprint

View full text Add to dashboard Cite

Objective -Endothelial progenitor cells (EPCs) promote the maintenance of the endothelium by the secretion of vasoreparative factors. A population of EPCs known as early outgrowth cells (EOCs) are currently being investigated as novel cell-based therapies for the treatment of cardiovascular disease. We previously demonstrated that the absence of liver x receptors (LXRs) is detrimental to the formation and function of EOCs under hypercholesterolemic conditions. Here, we investigate whether LXR gain-of-function in EOCs is beneficial for the treatment of atherosclerosis.Approach and Results -EOCs were differentiated from the bone marrow of wildtype (WT) and LXR-knockout (Lxrαβ-/-) mice in the presence of vehicle or LXR agonist (GW3965). WT EOCs treated with GW3965 throughout differentiation showed reduced expression of endothelial lineage markers (Cd144, Vegfr2) compared to WT vehicle and Lxrαβ-/cells. GW3965-treated EOCs produced secreted factors that reduced monocyte adhesion to activated endothelial cells in culture. When injected into atherosclerosis-prone Ldlr-/-mice, GW3965-treated EOCs and concentrated conditioned media (CM) from GW3965-treated EOCs, reduced plaque burden within the aortic sinus. Furthermore, when CM from human EOCs (obtained from patients with established CAD) were treated with GW3965, monocyte to endothelial adhesion was decreased suggesting the translatability of the results.

show abstract

Endothelial progenitor cell secretome delivered by novel polymeric nanoparticles in ischemic hindlimb

Cited by 26 publications

References 31 publications

PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

The Secretome of Liver X Receptor Agonist Treated Early Outgrowth Cells Decreases Atherosclerosis inLdlr-/- Mice

Contact Info

Product

Resources

About