Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

Harman, Rebecca M.; Marx, Charlotte; Walle, Gerlinde R. Van de

doi:10.3389/fcell.2021.654885

Cited by 27 publications

(32 citation statements)

References 216 publications

(209 reference statements)

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“…MSCs exert their functions through the secretome, including soluble proteins, nucleic acids, and lipids, which show similar effects to those MSCs. 39 , 40 Therefore, we next investigated whether PO-MSCs promoted EMT and epithelial barrier destruction in pHNECs by secreted proteins, including IGFBP2, matrix metalloproteinase 9 (MMP9), monocyte chemotactic protein-1 (MCP-1), vascular endothelial growth factor A (VEGFA) and interleukin-1β (IL-1β), all of which are associated with pathogenic biological behaviors. 26 , 41 , 42 Remarkably, compared with mock control and PO-MSCs-EVs, only IGFBP2 was significantly enriched in PO-MSCs-CM ( Figure 5 A).…”

Section: Resultsmentioning

confidence: 99%

IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps

You¹,

Zhang²,

Zhang³

et al. 2023

iScience

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Section: Resultsmentioning

confidence: 99%

IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps

You¹,

Zhang²,

Zhang³

et al. 2023

iScience

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“…These promising compounds are currently being tested in combination with standard chemotherapy or allogenic transplantation settings in clinical trials of high-risk MDS and refractory AML patients ( Martínez-Cuadrón et al, 2018 ; Roboz et al, 2018 ; Michelis et al, 2019 ; Bose et al, 2020 ). On the other hand, the anti-tumoral effects displayed by MSCs were attributed to small secreted factors ( Maguire, 2013 ; Moll et al, 2020 ; Wu et al, 2020 ) and led to increased interest in the use of MSC secretome for anti-leukemic therapy as well as for a wide array of other diseases, such as ischemic, neuroinflammatory and pulmonary malignancies (reviewed in Harman et al, 2021 ). Collective proteomic studies demonstrated that the MSC secretome consists of trophic factors (e.g., FGF, HGF, VEGF), cytokines (e.g., IL-6, TGFβ-1…), hormones, small peptides (e.g., SCF, PTG, Leptin) and extracellular vesicles (EVs) containing miRNA, mRNA and biologically active proteins ( Chulpanova et al, 2018 ).…”

Section: Msc Heterogeneity In Myeloid Malignanciesmentioning

confidence: 99%

Dynamic Changes of the Bone Marrow Niche: Mesenchymal Stromal Cells and Their Progeny During Aging and Leukemia

Woods

Guezguez

2021

Front. Cell Dev. Biol.

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Mesenchymal stromal cells (MSCs) are a heterogenous cell population found in a wide range of tissues in the body, known for their nutrient-producing and immunomodulatory functions. In the bone marrow (BM), these MSCs are critical for the regulation of hematopoietic stem cells (HSC) that are responsible for daily blood production and functional immunity throughout an entire organism’s lifespan. Alongside other stromal cells, MSCs form a specialized microenvironment BM tissue called “niche” that tightly controls HSC self-renewal and differentiation. In addition, MSCs are crucial players in maintaining bone integrity and supply of hormonal nutrients due to their capacity to differentiate into osteoblasts and adipocytes which also contribute to cellular composition of the BM niche. However, MSCs are known to encompass a large heterogenous cell population that remains elusive and poorly defined. In this review, we focus on deciphering the BM-MSC biology through recent advances in single-cell identification of hierarchical subsets with distinct functionalities and transcriptional profiles. We also discuss the contribution of MSCs and their osteo-adipo progeny in modulating the complex direct cell-to-cell or indirect soluble factors-mediated interactions of the BM HSC niche during homeostasis, aging and myeloid malignancies. Lastly, we examine the therapeutic potential of MSCs for rejuvenation and anti-tumor remedy in clinical settings.

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“…The most concerning are 3D culture, hypoxia, genetic engineering, cytokine pretreatment, etc. [ 10 , 11 ]. Previous studies have verified that stem cell preconditioning could dynamically alter the composition of their secretome.…”

Section: Introductionmentioning

confidence: 99%

ADSCs stimulated by VEGF-C alleviate intestinal inflammation via dual mechanisms of enhancing lymphatic drainage by a VEGF-C/VEGFR-3-dependent mechanism and inhibiting the NF-κB pathway by the secretome

Zhang

Wang

et al. 2022

Stem Cell Res Ther

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Background Adipose-derived stem cells (ADSCs) have provided promising applications for Crohn’s disease (CD). However, the practical efficacy of ADSCs remains controversial, and their mechanism is still unclear. Based on the pathogenesis of dysregulated immune responses and abnormal lymphatic alterations in CD, vascular endothelial growth factor-C (VEGF-C) is thought to be a favourable growth factor to optimize ADSCs. We aimed to investigate the efficacy of VEGF-C-stimulated ADSCs and their dual mechanisms in both inhibiting inflammation “IN” and promoting inflammation “OUT” in the intestine. Methods Human stem cells isolated from adipose tissues were identified, pretreated with or without 100 ng/ml VEGF-C and analysed for the secretion of cell culture supernatants in vitro. Lymphatic endothelial cells (LECs) were treated with ADSCs-conditioned medium or co-cultured with ADSCs and VEGF-C stimulated ADSCs. Changes in LECs transmigration, and VEGF-C/VEGFR-3 mRNA levels were assessed by transwell chamber assay and qRT–PCR. ADSCs and VEGF-C-stimulated ADSCs were intraperitoneally injected into mice with TNBS-induced chronic colitis. ADSCs homing and lymphatic vessel density (LVD) were evaluated by immunofluorescence staining. Lymphatic drainage was assessed using Evans blue. Cytokines and growth factors expression was detected respectively by ELISA and qRT–PCR. The protein levels of VEGF-C/VEGFR-3-mediated downstream signals and the NF-κB pathway were assayed by western blot. Faecal microbiota was measured by 16S rRNA sequencing. Results ADSCs stimulated with VEGF-C released higher levels of growth factors (VEGF-C, TGF-β1, and FGF-2) and lower expression of cytokines (IFN-γ and IL-6) in cell supernatants than ADSCs in vitro (all P < 0.05). Secretome released by VEGF-C stimulated ADSCs exhibited a stronger LEC migratory capability and led to elevated VEGF-C/VEGFR-3 expression, but these effects were markedly attenuated by VEGFR-3 inhibitor. VEGF-C-stimulated ADSCs homing to the inflamed colon and mesenteric lymph nodes (MLNs) can exert stronger efficacy in improving colitis symptoms, reducing inflammatory cell infiltration, and significantly enhancing lymphatic drainage. The mRNA levels and protein concentrations of anti-inflammatory cytokines and growth factors were markedly increased with decreased proinflammatory cytokines in the mice treated with VEGF-C-stimulated ADSCs. Systemic administration of VEGF-C-stimulated ADSCs upregulated the colonic VEGF-C/VEGFR-3 pathway and activated downstream AKT and ERK phosphorylation signalling, accompanied by decreased NF-κB p65 expression. A higher abundance of faecal p-Bacteroidetes and lower p-Firmicutes were detected in mice treated with VEGF-C-stimulated ADSCs (all P < 0.05). Conclusion VEGF-C-stimulated ADSCs improve chronic intestinal inflammation by promoting lymphatic drainage and enhancing paracrine signalling via activation of VEGF-C/VEGFR-3-mediated signalling and inhibition of the NF-κB pathway. Our study may provide a new insight into optimizing ADSCs treatment and investigating potential mechanisms in CD.

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Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

Cited by 27 publications

References 216 publications

IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps

IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps

Dynamic Changes of the Bone Marrow Niche: Mesenchymal Stromal Cells and Their Progeny During Aging and Leukemia

ADSCs stimulated by VEGF-C alleviate intestinal inflammation via dual mechanisms of enhancing lymphatic drainage by a VEGF-C/VEGFR-3-dependent mechanism and inhibiting the NF-κB pathway by the secretome

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