Placental mesenchymal stromal cells as an alternative tool for therapeutic angiogenesis

Mathew, Suja Ann; Naik, Charuta; Cahill, Paul A.; Bhonde, Ramesh

doi:10.1007/s00018-019-03268-1

Cited by 77 publications

(60 citation statements)

References 106 publications

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“…EVs, in particular, have been confirmed as the principal factor contributing to the paracrine function-mediated therapeutic efficacy of donor cells [37]. These nanosized EVs are lipid bilayer structures containing proteins, nucleic acids, and lipids that can contribute to intercellular communications by transferring these specific molecules, further exerting biological effects [38,39]. In fact, EVs are attractive as therapeutics due to their cellular-related advantages, such as high stability, no risk of aneuploidy, and low propensity to trigger immune rejection following allogeneic administration [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth

Zhou

Yin

et al. 2020

Stem Cell Res Ther

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Background: Although dental pulp stem cells (DPSCs) isolated from periodontally compromised teeth (P-DPSCs) have been demonstrated to retain pluripotency and regenerative potential, their use as therapeutics remains largely unexplored. In this study, we investigated the proangiogenic effects of extracellular vesicles (EVs) secreted by P-DPSCs using in vitro and in vivo testing models. Methods: Patient-matched DPSCs derived from periodontally healthy teeth (H-DPSCs) were used as the control for P-DPSCs. Conditioned media (CMs) derived from H-DPSCs and P-DPSCs (H-CM and P-CM), CMs derived from both cell types pretreated with the EV secretion blocker GW4869 (H-GW and P-GW), and EVs secreted by H-DPSCs and P-DPSCs (H-EVs and P-EVs) were prepared to test their proangiogenic effects on endothelial cells (ECs). Cell proliferation, migration, and tube formation were assessed using the Cell Counting Kit-8 (CCK-8), transwell/scratch wound healing, and Matrigel assays, respectively. Specifically, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analysis were used to examine the expression levels of angiogenesis-related genes/proteins in ECs in response to EV-based incubation. Finally, a full-thickness skin defect model was applied to test the effects of EVs on wound healing and new vessel formation.

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Section: Discussionmentioning

confidence: 99%

The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth

Zhou

Yin

et al. 2020

Stem Cell Res Ther

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“…Assays and data suggested that elevated HIF-1α expression level, induced by exosomes administration, led to the upregulation of proangiogenic growth factors both in vitro and in vivo. HIF-1α-overexpressed Dysregulation of angiogenesis and endothelial dysfunction are strongly associated with myocardial infarction [3,25]. Inadequate angiogenesis usually results in a shortage of oxygen and nutritional supply and consequently leads to elevated cell death [26].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, many attempts have been made in recent years on promoting angiogenesis to stimulate the recovery of the microvasculature. Angiogenesis is the process of new blood vessel formation from pre-existing vasculature and is often dysregulated in MI [3]. The rescue of impaired angiogenesis is a prerequisite for therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis

et al. 2020

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Background: Myocardial infarction (MI) is a severe disease that often associated with dysfunction of angiogenesis. Cell-based therapies for MI using mesenchymal stem cell (MSC)-derived exosomes have been well studied due to their strong proangiogenic effect. Genetic modification is one of the most common methods to enhance exosome therapy. This study investigated the proangiogenic and cardioprotective effect of exosomes derived from hypoxiainducible factor 1-alpha (HIF-1α)-modified MSCs. Methods: Lentivirus containing HIF-1α overexpressing vector was packaged and used to infect MSCs. Exosomes were isolated from MSC-conditioned medium by ultracentrifugation. Human umbilical vein endothelial cells (HUVECs) were treated under hypoxia condition for 48 h co-cultured with PBS, control exosomes, or HIF-1αoverexpressed exosomes, respectively. Then the preconditioned HUVECs were subjected to tube formation assay, Transwell assay, and EdU assay to evaluate the protective effect of exosomes. Meanwhile, mRNA and secretion levels of proangiogenic factors were measured by RT-qPCR and ELISA assays. In vivo assays were conducted using the rat myocardial infarction model. PBS, control exosomes, or HIF-1α-overexpressed exosomes were injected through tail vein after MI surgery. Heart function was assessed by echocardiography at days 3, 14, and 28. At day 7, mRNA and protein expression levels of proangiogenic factors in the peri-infarction area and circulation were evaluated, respectively. At day 28, hearts were collected and subjected to H&E staining, Masson's trichrome staining, and immunofluorescent staining. Results: HIF-1α-overexpressed exosomes rescued the impaired angiogenic ability, migratory function, and proliferation of hypoxia-injured HUVECs. Simultaneously, HIF-1α-overexpressed exosomes preserved heart function by promoting neovessel formation and inhibiting fibrosis in the rat MI model. In addition, both in vitro and in vivo proangiogenic factors mRNA and protein expression levels were elevated after HIF-1α-overexpressed exosome application.

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“…The VW-MSCs not only showed classical mesenchymal trilineage potential, but also differentiated toward endothelial phenotype and sustained the formation of capillary networks [23][24][25][26]. To date, the role of VW-MSCs in vascular regeneration has been intensely studied [27] and VW-MSCs are now emerging as a powerful tool for studying angiogenesis in physiological and pathological contexts [28].…”

Section: Introductionmentioning

confidence: 99%

Effects of Hydrogen Sulfide Donor NaHS on Porcine Vascular Wall-Mesenchymal Stem Cells

Bernardini

Mantia

Nesci

et al. 2020

IJMS

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Hydrogen sulfide (H2S) is now considered not only for its toxicity, but also as an endogenously produced gas transmitter with multiple physiological roles, also in maintaining and regulating stem cell physiology. In the present work, we evaluated the effect of a common H2S donor, NaHS, on porcine vascular wall–mesenchymal stem cells (pVW–MSCs). pVW–MSCs were treated for 24 h with increasing doses of NaHS, and the cell viability, cell cycle, and reactive oxygen species (ROS) production were evaluated. Moreover, the long-term effects of NaHS administration on the noteworthy characteristics of pVW–MSCs were analyzed. The MTT test revealed no alteration in cell viability, however, the cell cycle analysis demonstrated that the highest NaHS dose tested (300 μM) determined a block in S phase, which did not depend on the ROS production. Moreover, NaHS (10 μM), continuously administered in culture for 21 days, was able to significantly reduce NG2, Nestin and PDGFR-β expression. The pro-angiogenic attitude of pVW–MSCs was partially reduced by NaHS: the cells maintained the ability to grow in spheroid and sprouting from that, but endothelial markers (Factor VIII and CD31) were reduced. In conclusion, NaHS can be toxic for pVW–MSCs in high doses, while in low doses, it influences cellular physiology, by affecting the gene expression with a slowing down of the endothelial lineage.

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Placental mesenchymal stromal cells as an alternative tool for therapeutic angiogenesis

Cited by 77 publications

References 106 publications

The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth

The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth

HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis

Effects of Hydrogen Sulfide Donor NaHS on Porcine Vascular Wall-Mesenchymal Stem Cells

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