Clinical-grade human skin-derived ABCB5+ mesenchymal stromal cells exert modulatory functions on mRNA expression in a cisplatin-induced kidney injury murine model
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ABSTRACT:
PROVIDER: PRJNA927266 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23216714.fastq.gz | Fastqsanger.gz | |||
| SRR23216715.fastq.gz | Fastqsanger.gz | |||
| SRR23216716.fastq.gz | Fastqsanger.gz | |||
| SRR23216717.fastq.gz | Fastqsanger.gz | |||
| SRR23216718.fastq.gz | Fastqsanger.gz |
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Project description:Acute kidney injury (AKI) is characterized by a rapid reduction in renal function and glomerular filtration rate (GFR). The broadly used anti-cancer chemotherapeutic agent cisplatin often induces AKI as an adverse drug side effect. Therapies targeted at the reversal of AKI and its potential progression to chronic kidney disease or end-stage renal disease are currently insufficiently effective. Mesenchymal stromal cells (MSC) possess diverse immunomodulatory properties that confer upon them significant therapeutic potential for the treatment of diverse inflammatory disorders. Human dermal MSCs expressing ATP-Binding Cassette member B5 (ABCB5) have shown therapeutic efficacy in clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. In preclinical studies, ABCB5+ MSCs have also been shown to reverse metabolic reprogramming in polycystic kidney cells, suggesting a capacity for this cell subset to also improve organ function in kidney diseases. Here, we aimed to explore the therapeutic capacity of ABCB5+ MSCs to improve renal function in a preclinical rat model of cisplatin-induced AKI. First, ABCB5+ MSCs suppressed cisplatin-induced apoptosis of human conditionally-immortalized proximal tubular epithelial cells in vitro. Second, ABCB5+ MSCs inhibited the proliferation of either human or rat peripheral blood mononuclear cells. Third, ABCB5+ MSCs decreased TNF-α secretion after LPS stimulation in both human and rat macrophages. Fourth, clinical-grade ABCB5+ MSCs grafted intravenously and intraperitoneally to a cisplatin-induced AKI murine model exerted modulatory effects on mRNA expression patterns towards an anti-inflammatory and pro-regenerative state despite an apparent lack of amelioration of renal damage at physiologic, metabolic, and histologic levels. Our results demonstrate anti-inflammatory and pro-regenerative effects of clinical grade ABCB5+ MSCs in vitro and in vivo and suggest potential therapeutic utility of this cell population for treatment or prevention of cisplatin chemotherapy-induced tissue toxicity.
2024-01-04 | GSE223675 | GEO
Project description:We analyzed, by HTA 2.0, the GBM cell lines LN-18, LN-229, and U-87 MG after fluoresence-activated cell sorting (FACS) into ABCB5+ and ABCB5- fractions. Poor prognosis associated with glioblastoma multiforme (GBM) results from tumor resistance to therapy and high rate of recurrence. Compelling evidence suggests this is driven by subpopulations of slow-proliferating cancer stem cells with tumor-initiating potential. ATP-binding cassette member B5 (ABCB5) has been identified as a molecular marker for distinct subsets of chemoresistant tumor-initiating cell populations in diverse human malignancies. In the current study, we examined the potential role of ABCB5 in growth and chemoresistance of GBM. We found ABCB5 to be preferentially expressed in clinical GBM tumors and co-expressed with the stem cell marker CD133 in subpopulations of human GBM cell lines U-87 MG, LN-18 and LN-229. Antibody-mediated functional ABCB5 blockade inhibited proliferation and survival of human GBM cells and sensitized them to temozolomide (TMZ)-induced apoptosis. Likewise, in an in vivo GBM xenograft study in immunodeficient mice, anti-ABCB5 monoclonal antibody treatment inhibited tumor growth and sensitized tumors to TMZ therapy. Mechanistically, we demonstrated that ABCB5 regulates cell cycle checkpoint molecules to revoke drug-induced G2-M arrest and augments drug-mediated cell death. Overall, our data establish ABCB5 as a marker of GBM chemoresistance and point to the potential of ABCB5 targeting in improvement of current GBM therapies.
2020-03-05 | GSE127895 | GEO
Project description:Functional analysis of ABCB5 in A375 and G3361 melanoma cells, by comparing stably-transfected controls to ABCB5-shRNA-targeted cells. 12 samples total. Replicates n=3 for the following 4 groups: A375 pSUPER-retro-puro-Vector vs. A375 pSUPER-retro-puro-ABCB5-KD; G3361 pSUPER-retro-puro-shCNTRL vs. G3361 pSUPER-retro-puro-ABCB5-KD.
2014-06-17 | E-GEOD-38290 | biostudies-arrayexpress
Project description:Functional analysis of ABCB5 in A375 and G3361 melanoma cells, by comparing stably-transfected controls to ABCB5-shRNA-targeted cells.
2014-06-17 | GSE38290 | GEO
Project description:ABCB5 is marker for Limbal epithilal stem cells. A comparison between ABCB5+ versus ABCB5- cultured human limbal epithelial cells was carried out to evaluate the properties of the limbal stem cell ABCB5+ with a special focus on their role in inflammation and angiogenesis.
2023-10-24 | PXD041004 | Pride
Project description:Expression data from ABCB5-positive and ABCB5-negative GBM cells
| PRJNA525717 | ENA
Project description:Cancer stem cells (CSC) responsible for disease progression and therapeutic resistance have been identified in several human malignancies, including colorectal cancer (CRC). However, the molecular mechanisms through which CSC drive tumor growth are incompletely understood. ABCB5, a member of the ATP-binding cassette superfamily of active transporters, serves as a CSC-specific multidrug resistance mechanism in diverse human malignancies. Additionally, ABCB5 has recently been demonstrated to function as an anti-apoptotic gene in tissue-specific non-malignant stem cells. Here we demonstrate that ABCB5 also serves an anti-apoptotic role required for CSC maintenance in human cancer. Targeted inhibition of ABCB5, previously shown to be preferentially expressed on CD133-positive CRC stem cells, induced tumor cell apoptosis in vitro and in vivo and inhibited human CRC growth in NSG recipient mice. Mechanistically, ABCB5-positive tumor cell ablation through monoclonal antibody-mediated blockade or shRNA-mediated gene knockdown resulted in diminished production of the receptor tyrosine kinase AXL, a pro-tumorigenic molecule identified herein to be preferentially produced by CRC stem cells. Restoration of AXL expression through gene transfection in ABCB5 knockdown tumors partially restored tumor growth, demonstrating that ABCB5-positive CRC stem cells drive tumorigenicity at least in part through production of AXL. Our results establish a novel anti-apoptotic function of ABCB5 in human cancer and indicate that targeted blockade of ABCB5 represents a novel strategy for CSC eradication, independent of its previously established function as a multidrug resistance mediator.
2018-08-01 | GSE71670 | GEO
Project description:Defining markers of different phenotypic states in melanoma is important for understanding disease progression, determining the response to therapy, and defining the molecular mechanisms underpinning phenotype-switching driven by the changing intratumor microenvironment. The ABCB5 transporter is implicated in drug-resistance and has been identified as a marker of melanoma-initiating cells. Indeed, ongoing studies are using ABCB5 to define stem cell populations. However, we show here that the ABCB5 is a direct target for the Microphthalmia-associated transcription factor MITF and its expression can be induced by b-catenin, a key activator and co-factor for MITF. Consequently, ABCB5 mRNA expression is primarily associated with melanoma cells exhibiting differentiation markers. The results suggest first that ABCB5 is unlikely to represent a marker of dedifferentiated melanoma stem cells, and second that ABCB5 may contribute to the non-genetic drug-resistance associated with highly differentiated melanoma cells. To reconcile the apparently conflicting observations in the field we propose a model in which ABCB5 may mark a slow-cycling differentiated population of melanoma cells.
2019-10-16 | GSE136803 | GEO
Project description:Severe angiopathy has been postulated as a major driver for diabetes associated secondary complications. So far the knowledge on underlying mechanisms and thereon based therapeutic options to attenuate these pathologies are limited. Here we systematically administered ABCB5+ MSCs for the treatment of chronic non-healing diabetic wounds employing db/db mice, a type II diabetes model as their number markedly declined during diabetes. We found that administration of ABCB5+ MSCs markedly accelerates wound closure in diabetic db/db mice as opposed to the vehicle treated control group. Strikingly, administration of ABCB5+ MSCs at the edges of the diabetic wounds triggered considerable neoangiogenesis, most likely by the releasing a Ribonuclease angiogenin that was identified through secretome analysis of ABCB5+ MSCs. Interestingly, silencing of angiogenin in ABCB5+ MSCs significantly delayed wound closure in diabetic db/db mice indicating its key role in skin regeneration. Moreover, angiogenin also impacted the polarization of macrophages. The findings from this study will provide novel insight into the unique capacity of ABCB5+ MSCs to mount an adaptive response at the wound site with the delivery of angiogenic molecules holds significant promise for the therapy of non-healing diabetes foot ulcers, and other pathologies with impaired angiogenesis. The benefits for refined stem cell based therapies is virtually unlimited.
2020-01-24 | GSE144169 | GEO
Project description:We performed single cell RNA-seq of human ABCB5-positive limbal stem cells (LSCs) to examine their homogeneity.
2022-08-09 | GSE156524 | GEO