Hematopoietic Support Capacity of Mesenchymal Stem Cells: Biology and Clinical Potential

Fajardo-Orduña, Guadalupe R.; Mayani, Héctor; Montesinos, Juan José

doi:10.1016/j.arcmed.2015.10.001

Cited by 61 publications

(46 citation statements)

References 63 publications

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“…This is because MSCs generate most of the stromal cells present in the bone marrow (BM) and form part of the haematopoietic stem cell niche. The haematopoiesis‐supporting capacities of MSCs have been demonstrated previously (Fajardo‐Orduna et al , ). Cell‐cell interactions and cytokine secretion simultaneously contribute to differentiation in terminal MK lineage cells as well as platelet production within the BM niche.…”

Section: Discussionmentioning

confidence: 55%

Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the TNFAIP3/NF‐κB/SMAD pathway in patients with immune thrombocytopenia

Feng

et al. 2018

Br J Haematol

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Immune thrombocytopenia (ITP) is an autoimmune disease. Mesenchymal stem cells (MSCs) play important roles in the physiology and homeostasis of the haematopoietic system, including supporting megakaryocytic differentiation from CD34 haematopoietic progenitor cells. Tumour necrosis factor alpha-induced protein 3 (TNFAIP3, also termed A20) plays a key role in terminating NF-κB signalling. Human genetic studies showed that the polymorphisms of the TNFAIP3 gene may contribute to ITP susceptibility. In this study, we showed a significant decrease in TNFAIP3 and increase in NF-κB/SMAD7 in ITP-MSCs. In co-cultures with CD34 cells, NF-κB was overexpressed in MSCs from healthy controls (HC-MSCs) after transfection with NFKBIA (IκB)-specific short hairpin (sh)RNAs, resulting in MSC deficiency and a reduction in megakaryocytic differentiation and thrombopoiesis. Knockdown of TNFAIP3 expression using TNFAIP3-specific shRNAs in HC-MSCs affected megakaryocytopoiesis. However, IKBKB knockdown corrected megakaryocytopoiesis inhibition in the ITP-MSCs by decreasing NF-κB expression. Amplified TNFAIP3 expression in ITP-MSCs by TNFAIP3 cDNA can facilitate megakaryocyte differentiation. shRNA-mediated knockdown of SMAD7 expression rescued the impaired MSC function in ITP patients. Therefore, we demonstrate that a pathological reduction in TNFAIP3 levels induced NF-κB/SMAD7 pathway activation, causing a deficiency in MSCs in ITP patients. The ability of ITP-MSCs to support megakaryocytic differentiation and thrombopoiesis of CD34 cells was impaired.

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Section: Discussionmentioning

confidence: 55%

Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the TNFAIP3/NF‐κB/SMAD pathway in patients with immune thrombocytopenia

Feng

et al. 2018

Br J Haematol

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“…Regarding their therapeutic potential, several properties were associated with MSCs highlighting thus the importance of their use for different therapeutic purposes. Today, it is widely accepted that MSCs are actively involved in the hematopoiesis support (910). MSC are part of the highly specialized “bone marrow microenvironment” and are critical for forming the niche that maintains Hematopoietic Stem Cells (HSCs).…”

Section: Mesenchymal Stromal Cellsmentioning

confidence: 99%

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

et al. 2017

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Mesenchymal Stromal Cells (MSCs) are potential cellular candidates for several immunotherapy purposes. Their multilineage potential and immunomodulatory properties make them interesting tools for the treatment of various immunological diseases. However, depending on the local microenvironment, diverse biological functions of MSCs can be modulated. Indeed, during infections such as obtained following TLR-agonist engagement (called as TLR priming), the phenotype, multilineage potential, hematopoietic support and immunomodulatory capacity of MSCs can present critical changes, which could further affect their therapeutic potential. Thus, for appropriate clinical application of MSCs, it is important to well know and understand these effects in particular during infectious episodes and to find the suitable experimental settings to study that. Pre-stimulation of MSCs with a specific TLR ligand may serve as an effective priming step to modulate one of its function to achieve a desired therapeutic issue.

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“…12 They release a variety of hematopoiesis-regulating molecules and extracellular vesicles controlling functional characteristic of HSCs such as quiescence, self-renewal, and differentiation. [13][14][15][16] Various studies have used MSCs as a feeder layer for the ex vivo expansion and differentiation of HSCs toward megakaryocytic progenitors. 14,[17][18][19] MSCs produce low levels of thrombopoietin (TPO), which synergizes with other cytokines such as IL-6, IL-11, and stem cell factor (SCF) for megakaryocyte differentiation in the absence of exogenous cytokines.…”

Section: Introductionmentioning

confidence: 99%

Effect of Mesenchymal Stem Cell-derived Microvesicles on Megakaryocytic Differentiation of CD34+ Hematopoietic Stem Cells

et al. 2020

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Purpose: Mesenchymal stem cells (MSCs) release hematopoietic cytokines, growth factors, and Microvesicles (MVs) supporting the hematopoietic stem cells (HSCs). MVs released from various cells, playing a crucial role in biological functions of their parental cells. MSC-derived MVs contain microRNAs and proteins with key roles in the regulation of hematopoiesis. Umbilical cord blood (UCB) is a source for transplantation but the long-term recovery of platelets is a main problem. Therefore, we intend to show that MSC-MVs are able to improve the differentiation of UCB-derived CD34+ cells to megakaryocyte lineage. Methods: In this descriptive study, MSCs were cultured in DMEM to collect the culture supernatant, which was ultracentrifuged for the isolation of MVs. HSCs were isolated from UCB using MACS method and cultured in IMDM supplemented with cytokines and MVs in three different conditions. Megakaryocyte differentiation was evaluated through the expression of specific markers and genes after 72 hours, and the data was analyzed by t test (P<0.05). Results: The expression of specific megakaryocyte markers (CD41 and CD61) in the presence of different concentrations of MSC-MVs did not show any significant difference. Also, the expression of specific genes of megakaryocyte lineage was compared with control group. The expression of GATA2 and c-Mpl was significantly increased, GATA1 was not significantly decreased, and FLI1 was significantly decreased. Conclusion: MSC-MVs could improve the expression of specific megakaryocyte genes; however, there was no significant expression of CD markers. Further studies, including the evaluation of late stages of megakaryocyte differentiation, are required to evaluate platelet production and shedding

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Hematopoietic Support Capacity of Mesenchymal Stem Cells: Biology and Clinical Potential

Cited by 61 publications

References 63 publications

Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the TNFAIP3/NF‐κB/SMAD pathway in patients with immune thrombocytopenia

Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the TNFAIP3/NF‐κB/SMAD pathway in patients with immune thrombocytopenia

Mesenchymal Stromal Cells and Toll-Like Receptor Priming: A Critical Review

Effect of Mesenchymal Stem Cell-derived Microvesicles on Megakaryocytic Differentiation of CD34+ Hematopoietic Stem Cells

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