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Mechanism of recovery following human stem cell-derived extracellular vesicle treatment to cerebral ischemia

ABSTRACT: Characterization of hMSC cell and EV revealed that hypoxia preconditioning upregulated 41 expression of metabolic proteins related to HIF signaling, neurogenesis and EV biogenesis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: li sun

LAB HEAD: Li Sun

PROVIDER: PXD041677 | Pride | 2025-07-21

REPOSITORIES: Pride

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			Action	DRS
	20220111_LS_1.msf	Msf
	20220111_LS_1.mzML	Mzml
	20220111_LS_1.mzid.gz	Mzid
	20220111_LS_10.msf	Msf
	20220111_LS_10.mzML	Mzml

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1 - 5 of 60

Publications

Cargo Analysis and MRI-Based Therapeutic Assessment of Iron Oxide Labelled Extracellular Vesicles of Hypoxia Human Stem Cells in Ischemic Stroke.

Helsper Shannon S Sun Li L Jeske Richard R Liu Chang C Athey Jacob J Yuan Xuegang X Grant Samuel C SC Li Yan Y

Journal of extracellular biology 20250717 7

Human mesenchymal stem cells (hMSCs) have been under investigation in preclinical and clinical settings for treating neurological disorders in recent years. Predominantly due to paracrine effects <i>in vivo</i>, hMSC-secreted extracellular vesicles (EVs) are at the forefront of these investigations. In this study, the therapeutic efficacy of hypoxia hMSCs and the secreted EVs labelled with iron oxides was evaluated in a preclinical model of ischemic stroke. Transcriptome and proteomics analysis ...[more]

PMID: 40678584

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Engineering Extracellular Vesicles by Three-dimensional Dynamic Culture of Human Mesenchymal Stem Cells

Project description:Extracellular vesicles (EVs) contain proteins, enzymes and metabolites that contribute to the therapeutic potential of human mesenchymal stem cells (hMSCs). However, scale-up production of hMSC EVs has become a major challenge. In current study, hMSCs were grown as 3D aggregates under wave motion to promote EV secretion (3D EVs). mRNA sequencing reveals global transcriptome alterations (e.g., upregulated Wnt, TNF, and Hippo signaling and downregulated cellular senescence) for 3D aggregates. Compared to 2D EVs, the quantity of 3D EVs was enhanced significantly with smaller size, higher miR-21 and miR-22 expression, and the altered protein cargo revealed by proteomics. 3D hMSC aggregates promote activation of the endosomal sorting complexes required for transport (ESCRT) pathway and ESCRT-independent pathway. In addition, 3D EVs rejuvenated stem cells expressing cellular senescence and modulated immune response determined by T lymphocyte and macrophage phenotype assays. In summary, this study provides a promising strategy for high-quality EV production from hMSCs with enhanced therapeutic potentials.

2022-08-12 | PXD028975 | Pride

EBV Latent membrane protein1 modifies EV content

Project description:Extracellular vesicles (EV) mediate intercellular communication events and alterations in normal vesicle content contribute to function and disease initiation or progression. The ability to package a variety of cargo and transmit molecular information between cells renders EVs important mediators of cell to cell crosstalk. Latent membrane protein 1 (LMP1) is a chief viral oncoprotein expressed in most Epstein-Barr virus (EBV)-associated cancers and is released from cells at high levels in EVs. LMP1 containing EVs have been demonstrated to promote cell growth, migration, differentiation, and regulate immune cell function. Despite these significant changes in recipient cells induced by LMP1 modified EVs, the mechanism how this viral oncogene modulates the recipient cells towards these phenotypes is not well understood. We hypothesize that LMP1 alters EV content and following uptake of the LMP1-modified EVs by the recipient cells results in the activation of cell signaling pathways and increased gene expression which modulates the biological properties of recipient cell towards a new phenotype. Our results show that LMP1 expression alters the EV protein and microRNA content packaged into EVs.

2020-11-03 | PXD021914 | Pride

Transcription profiling of human control (hMSC-TERT) vs Dlk overexpressing cells (hMSC-Dlk1) to analyse Dlk1-mediated signaling pathways during hMSC differentiation

Project description:We aimed in this study to identify the differentially regulated genes by Dlk1 in hMSC cells using microarray technology in order to gain a better understanding of Dlk1-mediated signaling pathways during hMSC differentiation. Both control (hMSC-TERT)(not expressing Dlk1) and Dlk1 overexpressing cells (hMSC-Dlk1) were cultured in triplicate at 3×104 cells/cm2 in Petri-dish in standard growth medium. At 90-100% confluence, highly purified total cellular RNA was isolated from each of three independent cultures per cell line using RNeasy Kit (QIAGEN Nordic, West Sussex, UK) according to the manufacturer?s instructions

2006-02-10 | E-MEXP-560 | biostudies-arrayexpress

miRNA anlysis of extracellular vesicles (EV) secreted by embryonic stem cell-derived cardiovascular progenitor cells (hES-CPg) which recapitulate the therapeutic effects of these cells in a model of chronic heart failure (CHF).

Project description:Background: We have found that extracellular vesicles (EV) secreted by embryonic stem cell-derived cardiovascular progenitor cells (hES-CPg) recapitulate the therapeutic effects of these cells in a model of chronic heart failure (CHF). Objectives: Our goal was to test other cellular sources of EV and to explore their mechanism of action.

2017-10-06 | E-MTAB-5165 | biostudies-arrayexpress

Extracellular vesicles (EV) secreted by embryonic stem cell-derived cardiovascular progenitor cells (hES-CPg) recapitulate the therapeutic effects of these cells in a model of chronic heart failure (CHF).

2017-10-06 | E-MTAB-5164 | biostudies-arrayexpress

Extracellular Vesicles from patients with Antibody-Mediated Rejection induce tubular senescence and endothelial to mesenchymal transition by regulating complement activation through horizontal transfer of miRNAs

Project description:Extracellular vesicles (EV) has been shown to deliver potential microRNA (miRNA) as cargo for specific target cells; effectively, the EV unique nature of the bilayer allows miRNA to be protected from degradation. We used microarray analysis to compare the miRNA profiles of EV isolated from acute antibody-mediated allograft rejection patients (AAMR) and chronic antibody-mediated allograft rejection (CAMR) compared to Tx Controls patients. By microarray miRNA profiling we detected 42 miRNAs downregulated and 34 miRNAs upregulated with FDR < 0.05 and Fold change >2. Principal Component analysis showed that these 76 miRNAs were able to distinguish AMR-derived EV from healthy TX patients. We also investigated whether differences in EV miRNA content could separate AAMR and CAMR patients. We found 9 miRNAs differentially expressed in the two AMR groups (eight downregulated and only one upregulated in AAMR compared to CAMR; effectively, these miRNAs could distinguish AAMR-derived EV from CAMR-derived EV. We then investigated the possible target genes of these miRNAs according to their expression, fold change and the p value; interestingly, several targets were associated to CDKN1A and CDKN2A genes regulation.

2021-09-10 | E-MTAB-10447 | biostudies-arrayexpress

Mitochondria EglN1 drivers breast cancer progression by controlling metabolic adatation to hypoxic stress

Project description:Hypoxia is a hallmark of solid tumors. Mitochondria play essential roles in cellular adaptation to hypoxia, but the underlying mechanisms are not fully understood. Through mitochondrial proteomic profiling, we find that the prolyl hydroxylase EglN1 accumulates on mitochondria under hypoxia. EglN1 substrate binding region 23 loop is responsible for its mitochondrial translocation and contributes to tumor growth. Furthermore, we identify AMPK as an EglN1 substrate on mitochondria. The EglN1-AMPK interaction is essential for their mutual mitochondrial translocation. EglN1 prolyl-hydroxylates AMPK under normoxia, then they rapidly dissociate following prolyl-hydroxylation, leading to their immediate release from mitochondria. While hypoxia results in constant EglN1-AMPK interaction and accumulation on mitochondria, leading to the formation of CaMKK2-EglN1-AMPK complex to activate AMPK phosphorylation, consequently ensuring metabolic homeostasis and tumor growth. Our findings demonstrate EglN1 as an oxygen-sensitive metabolic checkpoint signaling hypoxic stress to mitochondria through its 23 loop, revealing a therapeutic target for solid tumors.

2023-08-29 | PXD041653 | Pride

Human iPSC-derived cardiomyocytes under hypoxia/normoxia, treated with bone marrow or cardiac stromal cell extracellular vesicles

Project description:RNA-seq was performed on cultured human induced pluripotent cell derived cardiomyocytes (iPSC-CMs). There are four groups, with three samples per group: H1,H2,H3. Negative control. Healthy, normoxic iPSC-CMs D1,D2,D3. Positive control. iPSCs cultured under hypoxic (0-1% O2) for 48h with 2% v/v PBS as vehicle control EV1,EV2,EV3. Treatment 1. iPSCs cultured under hypoxic (0-1% O2) for 48h, with cardiac stromal cell derived extracellular vesicles, provided at a dose of 67ng/µl (2% v/v) EV21, EV23, EV24. Treatment 2 iPSCs cultured under hypoxic (0-1% O2) for 48h, with bone marrow mesenchymal stromal cell (BM-MSC) derived extracellular vesicles, provided at a dose of 67ng/µl (2% v/v) All EVs were isolated from cultured human cells using sequential centrifugation methods. Cells were cultured using commercial EV-depleted FBS to avoid contamination of bovine EVs. EVs were validated for CD81, CD9, ALIX positivity, and visualised by cryoEM. Particle to protein ratios were not different between cardiac and bone marrow EV isolates. Therefore EV doses were standardised so that the same dose by protein (67ng/µl) and EV number (~2,000 EVs per iPSC-CM) were added.

2024-10-02 | E-MTAB-13966 | biostudies-arrayexpress

Packaging of DNA:RNA hybrids in extracellular vesicles and their horizontal transfer in cancer

Project description:RNAs isolated from ZR751 (acceptors/responders) and BT474 (non-acceptors/non-responders) cells following education with EV-Hybridlow (EV-DNA from normoxic cancer cells) and EV-Hybridhigh (EV-DNA from IH-derived cancer cells) were sequenced.

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Expression profiling of human umbilical cord mesenchymal stem cell line hMSCs, human esophageal carcinoma cell line EC9706 and their hybrids EMFs.

Project description:Our findings demonstrate that hMSCs can inhibit the malignant phenotypes of ECs through induced cell fusion without potentially cancerous reprogramming. To further understand the differences between before-after cell fusion and the mechanism of suppression, we used gene expression profiling technology from Capitalbio to find out the differences between EC cells, hMSCs and their derived heterokaryons. Six dual channel Capitalbio 22K Human oligo arrays was used to hybrid six paired samples (EC9706-cy3+EMF1-cy5, EC9706-cy3+EMF2-cy5, EC9706-cy3+EMF3-cy5, EMF1-cy3+hMSCs-cy5, EMF3-cy3+hMSC-cy5, hMSC-cy3+EMF2-cy5).One replicate per array.

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