The Impact of Mesenchymal Stem Cells on Differentiation of Hematopoietic Stem Cells

Saleh, Mahshid; Shamsasanjan, Karim; Movassaghpourakbari, Aliakbar; Akbarzadehlaleh, Parvin; Molaeipour, Zahra

doi:10.15171/apb.2015.042

Cited by 43 publications

(41 citation statements)

References 67 publications

(44 reference statements)

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“…Additionally, there is general agreement that Wnt signaling is important in stem cell biology. The Wnt/β‐catenin signaling has been reported to maintain pluripotency in embryonic stem cells and is critical for the expansion of neural progenitors thereby increasing brain size (Miyabayashi et al, ; Mohammadian et al, ; Saleh, Shamsasanjan, Movassaghpourakbari, Akbarzadehlaleh, & Molaeipour, ; Sato, Meijer, Skaltsounis, Greengard, & Brivanlou, ; Zechner et al, ). The Wnt/beta‐catenin signaling is also required for neural differentiation of ES cells, fate decision in neural crest stem cells and Wnt3a has been reported to promote differentiation into both the neural and astrocytic lineages by inhibiting neural stem cell maintenance (Otero, Fu, Kan, Cuadra, & Kessler, ; Zechner et al, ).…”

Section: Signaling Through Wnt/β‐catenin Pathwaymentioning

confidence: 99%

The roles of Wnt/β‐catenin pathway in tissue development and regenerative medicine

Majidinia

Akhondian²,

Jahanban‐Esfahlani³

et al. 2018

Journal Cellular Physiology

103

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Regenerative medicine is a translational field which combines tissue engineering and molecular biology to construct spare organs or help injured or defective tissues to regenerate or restore their normal functions. This is particularly important with specific organs such as heart, central nervous system, retina, or limbs which possess very limited regenerative capacity. As such, regenerative medicine has received peculiar attention in the last decade. In this regard, Wnt/β-catenin signaling pathway has been subject to intensive research, since it plays many essential roles in the regulation of the progenitor cell fate, developmental decisions, proliferation during embryonic development, and adult tissue homeostasis. In this paper, we will briefly introduce Wnt/β-catenin signaling pathway and discuss how it integrally contributes to both stem and cancer stem cell maintenance. Finally, we summarize the current understanding of the role of Wnt/β-catenin signaling in the development and regeneration of heart, lung, liver, bone, and cartilage.

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Section: Signaling Through Wnt/β‐catenin Pathwaymentioning

confidence: 99%

The roles of Wnt/β‐catenin pathway in tissue development and regenerative medicine

Majidinia

Akhondian²,

Jahanban‐Esfahlani³

et al. 2018

Journal Cellular Physiology

103

View full text Add to dashboard Cite

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“…MSCs secrete several cytokines that are related to proliferation and MK differentiation, including interleukin 6 (IL6), stem cell factor (SCF, also termed KITLG), granulocyte colony‐stimulating factor (G‐CSF) and granulocyte‐macrophage colony‐stimulating factor (GMCSF). MSCs can also directly interact with haematopoietic cells and MKs by expressing a number of adhesion molecules and integrins (Saleh et al , ).…”

mentioning

confidence: 99%

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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“…19 Moreover, MSCs alleviate the progenitor's injuries by ameliorating the microenvironment and secreted cytokines; improve proliferation and differentiation of HSCs. 20 Even though MSC affect PI3K/PTEN/AKT pathway based on the preliminary WB data, it is unjustified to conclude that this pathway is essential in inducing AML.…”

Section: Discussionmentioning

confidence: 99%

“…22 MSCs play a role in homing of HSCs in BM, support the long term of hematopoiesis and maintaining HSCs in an undifferentiated state. 20 Closing the contact between MSCs and HSCs props the differentiation of HSCs toward mature red cells. 20 MSCs provide soluble factors, contact-dependent interactions, and physical support to control HSCs self-renewal, quiescence, and differentiation 23 via direct cell contact and via the production of various cytokines, growth factors, and extracellular matrix (ECM) molecules.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model

Ahmed

Medhat

et al. 2019

Tumour Biol.

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Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis. This study was performed to analyze the role of mesenchymal stem cells as an alternative for cellular signaling growth factors involved in the pathogenesis of leukemogenesis in rats. Treatment of rats with 7,12-dimethyl benz [a] anthracene induced leukemogenesis appeared as a significant decrease in hematological parameters with concomitant significant increase in bone marrow oxidative and inflammatory indices (transforming growth factor beta and interleukin-6) in comparison with normal groups. On the contrary, Western immunoblotting showed a significant increase in the signaling growth factors: PI3K, AKT, mTOR proteins and a significant decrease in PTEN in 7,12-dimethyl benz [a] anthracene-treated group. In addition, a significant increase in the transcript levels of B cell lymphoma-2 protein gene in the 7,12-dimethyl benz [a] anthracene group, while that of C-X-C motif chemokine receptor-4 and B cell lymphoma-2 protein associated x-protein were significantly downregulated compared to controls. Meanwhile, therapeutic mesenchymal stem cells treatment predict a significant improvement versus 7,12-dimethyl benz [a] anthracene group through the modulation of growth factors that confront bone marrow dysplasia. In the same direction treatment of 7,12-dimethyl benz [a] anthracene group with mesenchymal stem cells, it induced apoptosis and increased the homing efficacy to bone marrow. In conclusion, mesenchymal stem cells improve hematopoiesis and alleviate inflammation, and modulated PI3K/AKT signaling pathway contributed to experimental leukemogenesis.

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The Impact of Mesenchymal Stem Cells on Differentiation of Hematopoietic Stem Cells

Cited by 43 publications

References 67 publications

The roles of Wnt/β‐catenin pathway in tissue development and regenerative medicine

The roles of Wnt/β‐catenin pathway in tissue development and regenerative medicine

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

Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model

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