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Bone marrow-derived cells and their conditioned medium induce microvascular repair in uremic rats by stimulation of endogenous repair mechanisms.

ABSTRACT: The reduced number of circulating stem/progenitor cells that is found in chronic kidney disease (CKD) patients may contribute to impaired angiogenic repair and decreased capillary density in the heart. Cell therapy with bone marrow-derived cells (BMDCs) has been shown to induce positive effects on the microvasculature and cardiac function, most likely due to secretion of growth factors and cytokines, all of which are present in the conditioned medium (CM); however, this is controversial. Here we showed that treatment with BMDC or CM restored vascular density and decreased the extent of fibrosis in a rat model of CKD, the 5/6 nephrectomy. Engraftment and differentiation of exogenous BMDCs could not be detected. Yet CM led to the mobilization and infiltration of endogenous circulating cells into the heart. Cell recruitment was facilitated by the local expression of pro-inflammatory factors such as the macrophage chemoattractant protein-1, interleukin-6, and endothelial adhesion molecules. Consistently, in vitro assays showed that CM increased endothelial adhesiveness to circulating cells by upregulating the expression of adhesion molecules, and stimulated angiogenesis/endothelial tube formation. Overall, our results suggest that both treatments exert vasculoprotective effects on the heart of uremic rats by stimulating endogenous repair mechanisms.

SUBMITTER: Golle L

PROVIDER: S-EPMC5572734 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Bone marrow-derived cells and their conditioned medium induce microvascular repair in uremic rats by stimulation of endogenous repair mechanisms.

Golle Lina L Gerth Hans U HU Beul Katrin K Heitplatz Barbara B Barth Peter P Fobker Manfred M Pavenstädt Hermann H Di Marco Giovana S GS Brand Marcus M

Scientific reports 20170825 1

The reduced number of circulating stem/progenitor cells that is found in chronic kidney disease (CKD) patients may contribute to impaired angiogenic repair and decreased capillary density in the heart. Cell therapy with bone marrow-derived cells (BMDCs) has been shown to induce positive effects on the microvasculature and cardiac function, most likely due to secretion of growth factors and cytokines, all of which are present in the conditioned medium (CM); however, this is controversial. Here we ...[more]

PMID: 28842629

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Project description:BackgroundOligovascular niche mediates interactions between cerebral endothelial cells and oligodendrocyte precursor cells (OPCs). Disruption of OPC-endothelium trophic coupling may aggravate the progress of cerebral white matter injury (WMI) because endothelial cells could not provide sufficient support under diseased conditions. Endothelial progenitor cells (EPCs) have been reported to ameliorate WMI in the adult brain by boosting oligovascular remodeling. It is necessary to clarify the role of the conditioned medium from hypoxic endothelial cells preconditioned EPCs (EC-pEPCs) in WMI since EPCs usually were recruited and play important roles under blood-brain barrier disruption. Here, we investigated the effects of EC-pEPCs on oligovascular remodeling in a neonatal rat model of WMI.MethodsIn vitro, OPC apoptosis induced by the conditioned medium from oxygen-glucose deprivation-injured brain microvascular endothelial cells (OGD-EC-CM) was analyzed by TUNEL and FACS. The effects of EPCs on EC damage and the expression of cytomokine C-X-C motif ligand 12 (CXCL12) were examined by western blot and FACS. The effect of the CM from EC-pEPCs against OPC apoptosis was also verified by western blot and silencing RNA. In vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia and treated with EPCs or EC-pEPCs at P7, and then angiogenesis and myelination together with cognitive outcome were evaluated at the 6th week.ResultsIn vitro, EPCs enhanced endothelial function and decreased OPC apoptosis. Meanwhile, it was confirmed that OGD-EC-CM induced an increase of CXCL12 in EPCs, and CXCL12-CXCR4 axis is a key signaling since CXCR4 knockdown alleviated the anti-apoptosis effect of EPCs on OPCs. In vivo, the number of EPCs and CXCL12 protein level markedly increased in the WMI rats. Compared to the EPCs, EC-pEPCs significantly decreased OPC apoptosis, increased vascular density and myelination in the corpus callosum, and improved learning and memory deficits in the neonatal rat WMI model.ConclusionsEC-pEPCs more effectively promote oligovascular remodeling and myelination via CXCL12-CXCR4 axis in the neonatal rat WMI model.

Project description:PurposeThis study aimed to investigate the effects of photobiomodulation (PBM) and conditioned medium (CM) derived from human adipose-derived stem cells (h-ASCs), both individually and in combination, on the maturation stage of an ischemic infected delayed healing wound model (IIDHWM) in type I diabetic (TIDM) rats.MethodsThe study involved the extraction of h-ASCs from donated fat, assessment of their immunophenotypic markers, cell culture, and extraction and concentration of CM from cultured 1 × 10^6 h-ASCs. TIDM was induced in 24 male adult rats, divided into four groups: control, CM group, PBM group (80 Hz, 0.2 J/cm2, 890 nm), and rats receiving both CM and PBM. Clinical and laboratory evaluations were conducted on days 4, 8, and 16, and euthanasia was performed using CO2 on day 16. Tensiometrical and stereological examinations were carried out using two wound samples from each rat.ResultsAcross all evaluated factors, including wound closure ratio, microbiological, tensiometrical, and stereological parameters, similar patterns were observed. The outcomes of CM + PBM, PBM, and CM treatments were significantly superior in all evaluated parameters compared to the control group (p = 0.000 for all). Both PBM and CM + PBM treatments showed better tensiometrical and stereological results than CM alone (almost all, p = 0.000), and CM + PBM outperformed PBM alone in almost all aspects (p = 0.000). Microbiologically, both CM + PBM and PBM exhibited fewer colony-forming units (CFU) than CM alone (both, p = 0.000).ConclusionPBM, CM, and CM + PBM interventions substantially enhanced the maturation stage of the wound healing process in IIDHWM of TIDM rats by mitigating the inflammatory response and reducing CFU count. Moreover, these treatments promoted new tissue formation in the wound bed and improved wound strength. Notably, the combined effects of CM + PBM surpassed the individual effects of CM and PBM.Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-023-01285-3.

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Bone marrow-derived cells and their conditioned medium induce microvascular repair in uremic rats by stimulation of endogenous repair mechanisms.

Publications

Bone marrow-derived cells and their conditioned medium induce microvascular repair in uremic rats by stimulation of endogenous repair mechanisms.

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