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Reduced proliferation capacity of native bone marrow MSC after allogenic stem cell transplantation is associated with clinical outcome

ABSTRACT: Reduced proliferation capacity of native bone marrow MSC after allogenic stem cell transplantation is associated with clinical outcome

PROVIDER: PRJNA839247 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19262400_1.fastq.gz	Fastqsanger.gz
	SRR19262400_2.fastq.gz	Fastqsanger.gz
	SRR19262401_1.fastq.gz	Fastqsanger.gz
	SRR19262401_2.fastq.gz	Fastqsanger.gz
	SRR19262402_1.fastq.gz	Fastqsanger.gz

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Reduced proliferation capacity of native bone marrow MSC after allogenic stem cell transplantation is associated with clinical outcome

Project description:Engraftment and differentiation of donor hematopoietic stem cells is decisive for the clinical success of allogeneic stem cell transplantation (alloSCT) and depends on the recipient’s bone marrow (BM) niche. Presumably, a damaged niche contributes to poor graft function post-alloSCT, but the underlying mechanisms and specifically the role of BM multipotent mesenchymal stroma cells (MSC) are ill defined. Upon multivariate analysis in a cohort of 732 individuals, we observed a reduced presence of proliferation-capable MSC in BM-aspirates from patients (N=196) who had undergone alloSCT (OR 0.61, p=.028). This was confirmed by paired analysis in 30 patients showing a higher frequency of samples with a lack of MSC presence post-alloSCT compared to pre-alloSCT. This reduced MSC presence was associated with reduced survival of patients following alloSCT and specifically with impaired graft function. Post-alloSCT MSC showed diminished in vitro proliferation along with a transcriptional antiproliferative signature, upregulation of epithelial-mesenchymal transition and extracellular matrix pathways and abnormal cytokine release in coculture with hematopoietic cells. In order to avoid in-vitro-culture bias we isolated the CD146+/CD45-/HLA-DR- BM cell fraction, which comprised the entire MSC population. The post-alloSCT isolated native CD146+MSC showed a similar reduction in proliferation capacity and shared the same antiproliferative transcriptomic signature as for post-alloSCT adherence-isolated MSC. Taken together, our data show that alloSCT confers damage to the proliferative capacity of native MSC, which is associated with reduced patient survival after alloSCT and impaired engraftment of allogeneic hematopoiesis. These data represent the basis to elucidate mechanisms of BM-niche reconstitution post-alloSCT and its therapeutic manipulation.

2023-05-01 | GSE203246 | GEO

The incorporation of extracellular vesicles from MSC into HSC increase their clonogenic capacity and engraftment ability

Project description:Treatment of graft failure after allogeneic stem cell transplantation with mesenchymal stromal cells (MSC) is being evaluated clinically. MSC can exert their functions by the release of extracellular vesicles (EV). Our aim is to analyze changes induced in hematopoietic stem cells (HSC) after the incorporation of MSC-EV. MSC were isolated from healthy donors. MSC-EV were isolated by ultracentrifugation and characterized by flow cytometry (FC), Western-blot, electron microscopy and Nanosight. EV incorporation into HSC was analyzed by FC and confocal microscopy. To study HSC gene expression, RT-PCR and arrays were performed. Apoptosis and cell cycle were evaluated by FC and clonal growth by clonogenic assays in methylcellulose. The engraftment capacity of HSC was analyzed four weeks after transplantation in NOD-SCID mice. Our results showed that MSC-EV presented the characteristic morphology, size and inmunophenotype and were able to be incorporated into HSC. MSC-EV incorporation induced an a down-regulation of pro-apoptotic genes, an overexpression of genes involved in colony formation and cell proliferation together with an activation of the JAK-STAT pathway in HSC. A significant decrease in apoptosis (p=0.001), an increase of the percentage of cells in phase S and an increased CD44 expression (p=0.013) were confirmed by FC in HSC with MSC-EV. In addition, these HSC displayed a higher CFU-GM clonogenic potential (p=0.010). Finally, in the xenotransplantation model, the engraftment ability of human HSC with MSC-EV was significantly higher (p= 0.027). In summary, the incorporation of MSC-EV induces genomic and functional changes in HSC, increasing their clonogenic capacity and their engraftment ability.

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Gene expression profiling in IBD rat treat with MSC transplantation

Project description:Investigation of whole genome gene expression level changes in Inflammatory bowel disease rats after MSC transplantation, compared to IBD control rats, and to explore the mechanism of MSC transplantation. A four chip study using total RNA recovered from two separate IBD rats after MSC transplantation and two separate IBD control rats. Each chip measures the expression level of 26,419 genes from normal rat and IBD rat treated with MSC transplantation.

2015-05-08 | E-GEOD-68653 | biostudies-arrayexpress

Gene expression profiling in IBD rat treat with MSC transplantation

2015-05-08 | GSE68653 | GEO

Gene Expression profile of brain in SCI rat by MSC intravenous transplantation.

Project description:We had analysed gene expression profile of brain in SCI rat by MSC. Compared with MSC intravenous and vehicle injection at SCI day3. We used Clariom D / Gene Chip® Rat Transcriptome Array (RTA 1.0., Affymetrix, Santa Clara, CA, USA).

2018-09-01 | GSE108168 | GEO

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Project description:A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age

2018-12-18 | GSE122473 | GEO

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Project description:Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation

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Effect of MSC and MSC-derived extracellular vesicles on human blood coagulation

Project description:Mesenchymal stem cells (MSC) have emerged as potent therapeutic tool for a number of pathologies, including immune ones. However, unwelcome effects of MSC on the blood coagulation were revealed in some cases, which require more in-depth analysis. In this study, we explored the trombotic properties of human MSC from umbilical cord. We revealed strong procoagulant effects of umbilical cord MSC toward human and rat whole blood and platelets-free plasma using rotational thromboelastometry and thrombodynamics tests. The similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EV). In order to suggest approaches to avoid unwanted effects we studied the impact of heparin supplement on MSC/EV procoagulation properties. We found that therapeutic doses of unfractionated heparin injected in the patient's blood (administered in vivo) did not abrogate the procoagulant properties of MSC. Mass-spectrometry analysis of proteins of MSC and EV involved in coagulation-associated pathways was used to evaluate mechanisms of protrombotic effects.

2019-03-26 | PXD012768 | Pride

The incorporation of extracellular vesicles from MSC into HSC increase their clonogenic capacity and engraftment ability

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Murine MSCs: MSC-exosome-hypoxia vs MSC-exosome-normoxia

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