Extracellular vesicles: Regenerative medicine prospect in hematological malignancies

Masoumipour, Maedeh; Abbaspanah, Bahareh; Mousavi, Seyed Hadi

doi:10.1002/cbin.11660

Cited by 5 publications

(4 citation statements)

References 69 publications

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“…Analyzing marker correlation patterns generates deeper insights into the mechanisms underlying AL development. The observed disruptions in correlations provide strong evidence for dysregulated cellular communication within leukemic blasts (Bewersdorf & Zeidan, 2020; Masoumipour et al, 2021). Our findings revealed intriguing patterns of disrupted correlations within specific lineages for each AL group.…”

Section: Discussionmentioning

confidence: 88%

Immunophenotype signatures in acute leukemias unveiled by integrative systems immunology

Bahia,

Lima,

de Medeiros Oliveira

et al. 2024

Preprint

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Acute leukemias (ALs) are complex hematological disorders, and accurate diagnosis is crucial for guiding treatment decisions and predicting patient outcomes. While changes in cell marker levels are well documented, the impact of these changes on marker relationships through an integrative systems approach remains uncharacterized. To address this gap, we conducted a 12-year study investigating 41 markers, including ontogenic markers and those used to diagnose both common and rare leukemia types, using immunophenotyping flow cytometry (IFC) data from 1,069 leukocyte samples obtained from peripheral blood (PB) or bone marrow (BM) aspirates of patients with suspected ALs. Machine learning techniques, such as principal component analysis (PCA) and random forest (RF) classification, demonstrated the stratification power of the cellular markers. Hierarchical clustering analysis of leukocyte ontogenetic markers revealed disease-specific clusters, irrespective of sex or sample type (PB or BM). Additionally, we found that patients with acute myeloid leukemia (AML) showed mild disruption in cell marker correlations, whereas the most significant dysregulation was observed in patients with T-cell acute lymphoblastic leukemia (T-ALL). Importantly, we identified ontogenic correlation changes indicating clusters of immature versus mature leukocyte markers, as well as cell lineage-specific markers influencing cellular relationships. These findings underscore the value of integrating systems strategies into conventional IFC analyses to enhance synthetic diagnosis and deepen our understanding of ALs pathophysiology.

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Section: Discussionmentioning

confidence: 88%

Immunophenotype signatures in acute leukemias unveiled by integrative systems immunology

Bahia,

Lima,

de Medeiros Oliveira

et al. 2024

Preprint

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“…In recent years, wide ranges of evidence showed that SC-derived secretomes contain heterogeneous extracellular vesicles (EVs), Exos, and microvesicles, with various growth factors, cytokines, lipids, nucleotides, and proteins to alleviate the pathological conditions and alter the healing process [22][23][24]. To this end, cell-free therapies have become a novel approach in regenerative medicine From a molecular aspect, Exos mimic the proteomic and genomic status of parent SCs, making them an alternative therapeutic instead of SCs [14].…”

Section: Cell-free Therapies and Exosomes (Exos)mentioning

confidence: 99%

“…Using various internalization mechanisms, ligand-based endocytosis, direct fusion, West Kazakhstan Medical Journal Halimeh Mobarak et al macropinocytosis, etc. facilitates the entry of cargo-loaded Exos into the target cells such as cancer cells [14,[22][23][24]. It is postulated that SC EVs are relatively safe as they are unable to replicate and differentiate unintendedly after administration in the body [14].…”

Section: Cell-free Therapies and Exosomes (Exos)mentioning

confidence: 99%

Stem Cell- and Stem Cell-Free-Based Therapies: Pros and Cons

Mobarak,

Rahbarghazi,

Mahdipour

2023

WKMJ

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The efficiency of stem cell (SC)-based therapies has been proven in numerous animal and human studies. Along with the differentiation into several lineages, it is quite evident that SCs convey significant therapeutic effects in a paracrine manner via releasing various nano-sized extracellular vesicles (EVs) containing cytokines and bioactive factors. Notably, recent trials have stated the lack of stability and durability of the transplanted SCs at the site of injury for long periods, leading to the restrictions of SC in regenerative outcomes. Thus, EVs especially exosomes (Exos) gained much attention for therapeutic purposes and delivery purposes to the injury site. In contrast to whole-SC-based therapies, Exos can be used with fewer side effects. However, it should not be forgotten that both whole-SC- and cell-free-based options possess inherent pros and cons that necessitate being carefully evaluated before application in the clinical setting. Here, the effectiveness and limitations associated with whole-SCand SC-free-based therapies in the clinical setting are briefly discussed.

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“…Compared to those diluted nucleotide pieces in the peripheral blood, the exosomal content is much more stable. Therefore, the value of analyzing exosome-encapsulated DNA/RNA has been recognized (Cheng et al, 2015 ; Ramirez et al, 2018 ), and the exosomes in liquid biopsy are commonly utilized to develop diagnostic tools in clinical applications (Grieco et al, 2021 ; Masoumipour et al, 2021 ; Zani-Ruttenstock et al, 2021 ). Among these, studies have shown that exosomes could be used for predicting Alzheimer’s disease (AD) and evaluating the severity of intellectual disability in patients with Parkinson’s disease and dementia (Cheng et al, 2015 ; Stuendl et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic immune and exosome transcriptomic responses in patients undergoing psychostimulant methamphetamine withdrawal

Zhang²,

Ma³

et al. 2022

Front. Cell. Neurosci.

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Methamphetamine (METH) addiction and withdrawal cause serious harm to both the immune system and nervous system. However, the pathogenesis remains largely unknown. Herein, we investigated the peripheral cytokines and exosomal transcriptome regulatory networks in the patients with METH use disorders (MUDs) undergoing withdrawal. Twenty-seven cytokines were simultaneously assessed in 51 subjects, including 22 at the acute withdrawal (AW) stage and 29 at the protracted withdrawal (PW) stage, and 31 age and gender-matched healthy controls (HCs). Compared to the HCs, significantly decreased levels of interleukin (IL)-1β, IL-9, IL-15, Basic FGF, and MIP1a, increased levels of IL-1rα, IL-6, Eotaxin IP-10, VEGF, and RANTES were identified in AW. These disturbances were mostly or partly restored to the baseline in PW. However, the cytokines IL-6, IL-7, and IL-12p70 were consistently increased even after one year of withdrawal. Besides, a significant decrease in CD3+T and CD4+T cell numbers was observed in AW, and the diminishment was restored to baseline in PW. Comparatively, there were no statistically significant changes in CD8+T, NK, and B cells. Furthermore, the exosomal mRNAs and long non-coding RNAs (lncRNA) were profiled, and the lncRNA-miRNA-mRNA networks were constructed and associated with METH AW and PW stages. Notably, the chemokine signaling was remarkably upregulated during AW. By contrast, the differentially expressed mRNAs/lincRNAs were significantly enriched in neurodegeneration-related diseases. Taken together, a group of METH withdrawal-related cytokines and exosomal mRNA/lncRNA regulatory networks were obtained, which provides a useful experimental and theoretical basis for further understanding of the pathogenesis of the withdrawal symptoms in MUDs.

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Extracellular vesicles: Regenerative medicine prospect in hematological malignancies

Cited by 5 publications

References 69 publications

Immunophenotype signatures in acute leukemias unveiled by integrative systems immunology

Immunophenotype signatures in acute leukemias unveiled by integrative systems immunology

Stem Cell- and Stem Cell-Free-Based Therapies: Pros and Cons

Dynamic immune and exosome transcriptomic responses in patients undergoing psychostimulant methamphetamine withdrawal

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