scholarly journals Cellular and Molecular Mechanisms Mediated by recPrPC Involved in the Neuronal Differentiation Process of Mesenchymal Stem Cells

2019 ◽  
Vol 20 (2) ◽  
pp. 345 ◽  
Author(s):  
Stefano Martellucci ◽  
Costantino Santacroce ◽  
Francesca Santilli ◽  
Luca Piccoli ◽  
Simona Delle Monache ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neuronal Differentiation ◽  
Lipid Rafts ◽  
Prion Protein ◽  
Signal Pathway ◽  
Differentiation Process ◽  
Akt Phosphorylation ◽  
Intracellular Signal

Human Dental Pulp Stem Cells (hDPSCs) represent a type of adult mesenchymal stem cells that have the ability to differentiate in vitro in several lineages such as odontoblasts, osteoblasts, chondrocytes, adipocytes and neurons. In the current work, we used hDPSCs as the experimental model to study the role of recombinant prion protein 23–231 (recPrPC) in the neuronal differentiation process, and in the signal pathway activation of ERK 1/2 and Akt. We demonstrated that recPrPC was able to activate an intracellular signal pathway mediated by extracellular-signal-regulated kinase 1 and 2 (ERK 1/2) and protein kinase B (Akt). Moreover, in order to understand whether endogenous prion protein (PrPC) was necessary to mediate the signaling induced by recPrPC, we silenced PrPC, demonstrating that the presence of endogenous PrPC was essential for ERK 1/2 and Akt phosphorylation. Since endogenous PrPC is a well-known lipid rafts component, we evaluated the role of these structures in the signal pathway induced by recPrPC. Our results suggest that lipid rafts integrity play a key role in recPrPC activity. In fact, lipid rafts inhibitors, such as fumonisin B1 and MβCD, significantly prevented ERK 1/2 and Akt phosphorylation induced by recPrPC. In addition, we investigated the capacity of recPrPC to induce hDPSCs neuronal differentiation process after long-term stimulation through the evaluation of typical neuronal markers expression such as B3-Tubulin, neurofilament-H (NFH) and growth associated protein 43 (GAP43). Accordingly, when we silenced endogenous PrPC, we observed the inhibition of neuronal differentiation induced by recPrPC. The combined data suggest that recPrPC plays a key role in the neuronal differentiation process and in the activation of specific intracellular signal pathways in hDPSCs.

scholarly journals The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor

2021 ◽  
Vol 22 (22) ◽  
pp. 12194
Author(s):  
Jin Hyoung Cho ◽  
Won Seok Ju ◽  
Sang Young Seo ◽  
Bo Hyun Kim ◽  
Ji-Su Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neuronal Differentiation ◽  
Nucleoside Diphosphate Kinase ◽  
Inhibitory Effect ◽  
Human Macrophage ◽  
Potential Candidate ◽  
Xenograft Rejection ◽  
Ganglioside Gd3

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.

scholarly journals Insulin-Like Growth Factor Binding Protein-6 Promotes the Differentiation of Placental Mesenchymal Stem Cells into Skeletal Muscle Independent of Insulin-Like Growth Factor Receptor-1 and Insulin Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Doaa Aboalola ◽  
Victor K. M. Han
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Muscle Differentiation ◽  
Insulin Like Growth Factor ◽  
Differentiation Process ◽  
Placental Mesenchymal Stem Cells

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation, in vitro, is vital in developing these cellular therapies to treat degenerative diseases. Muscle differentiation is a multistep process, starting with commitment to the muscle lineage and ending with the formation of multinucleated fibers. Insulin-like growth factor binding protein-6 (IGFBP-6), relative to other IGFBPs, has high affinity for IGF-2. However, the role of IGFBP-6 in muscle development has not been clearly defined. Our previous studies showed that in vitro extracellular IGFBP-6 increased myogenesis in early stages and could enhance the muscle differentiation process in the absence of IGF-2. In this study, we identified the signal transduction mechanisms of IGFBP-6 on muscle differentiation by placental mesenchymal stem cells (PMSCs). We showed that muscle differentiation required activation of both AKT and MAPK pathways. Interestingly, we demonstrated that IGFBP-6 could compensate for IGF-2 loss and help enhance the muscle differentiation process by triggering predominantly the MAPK pathway independent of activating either IGF-1R or the insulin receptor (IR). These findings indicate the complex interactions between IGFBP-6 and IGFs in PMSC differentiation into the skeletal muscle and that the IGF signaling axis, specifically involving IGFBP-6, is important in muscle differentiation. Moreover, although the major role of IGFBP-6 is IGF-2 inhibition, it is not necessarily the case that IGFBP-6 is the main modulator of IGF-2.

Role of lipid rafts in neuronal differentiation of dental pulp-derived stem cells

2015 ◽  
Vol 339 (2) ◽  
pp. 231-240 ◽  
Author(s):  
Vincenzo Mattei ◽  
Costantino Santacroce ◽  
Vincenzo Tasciotti ◽  
Stefano Martellucci ◽  
Francesca Santilli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neuronal Differentiation ◽  
Lipid Rafts ◽  
Dental Pulp

scholarly journals Prion Protein in Stem Cells: A Lipid Raft Component Involved in the Cellular Differentiation Process

2020 ◽  
Vol 21 (11) ◽  
pp. 4168 ◽  
Author(s):  
Stefano Martellucci ◽  
Costantino Santacroce ◽  
Francesca Santilli ◽  
Valeria Manganelli ◽  
Maurizio Sorice ◽  
...  
Keyword(s):  
Stem Cells ◽  
Prion Protein ◽  
Lipid Raft ◽  
Cellular Differentiation ◽  
Cell Types ◽  
Pleiotropic Effect ◽  
Cellular Prion Protein ◽  
Differentiation Process ◽  
Differentiation Degree

The prion protein (PrP) is an enigmatic molecule with a pleiotropic effect on different cell types; it is localized stably in lipid raft microdomains and it is able to recruit downstream signal transduction pathways by its interaction with various biochemical partners. Since its discovery, this lipid raft component has been involved in several functions, although most of the publications focused on the pathological role of the protein. Recent studies report a key role of cellular prion protein (PrPC) in physiological processes, including cellular differentiation. Indeed, the PrPC, whose expression is modulated according to the cell differentiation degree, appears to be part of the multimolecular signaling pathways of the neuronal differentiation process. In this review, we aim to summarize the main findings that report the link between PrPC and stem cells.

Potential role of N-benzylcinnamide in inducing neuronal differentiation from human amniotic fluid mesenchymal stem cells

2016 ◽  
Vol 610 ◽  
pp. 6-12 ◽  
Author(s):  
Wipawan Thangnipon ◽  
Nicha Puangmalai ◽  
Nirut Suwanna ◽  
Rungtip Soi-ampornkul ◽  
Ruchee Phonchai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Amniotic Fluid ◽  
Neuronal Differentiation ◽  
Potential Role ◽  
Human Amniotic Fluid

scholarly journals Role of Prion protein-EGFR multimolecular complex during neuronal differentiation of human dental pulp-derived stem cells

Prion ◽  
2018 ◽  
Vol 12 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Stefano Martellucci ◽  
Valeria Manganelli ◽  
Costantino Santacroce ◽  
Francesca Santilli ◽  
Luca Piccoli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neuronal Differentiation ◽  
Prion Protein ◽  
Dental Pulp ◽  
Human Dental Pulp

scholarly journals A Cocktail Method for Promoting Cardiomyocyte Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Qing Gao ◽  
Maojuan Guo ◽  
Xijuan Jiang ◽  
Xiantong Hu ◽  
Yijing Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Beta Catenin ◽  
Differentiation Process ◽  
Cardiomyocyte Differentiation ◽  
Cellular Environment ◽  
Growing Body ◽  
Real Time Qpcr

A growing body of evidence supports the argument that bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into cardiomyocyte-like cells in an appropriate cellular environment, but the differentiation rate is low. A cocktail method was designed: we investigated the role of 5-azacytidine (5-aza), salvianolic acid B (SalB), and cardiomyocyte lysis medium (CLM) in inducing MSCs to acquire the phenotypical characteristics of cardiomyocytes. The fourth-passage MSCs were treated with 5-aza, SalB, CLM, 5-aza+salB, 5-aza+CLM, SalB+CLM, and 5-aza+SalB+CLM for 2 weeks. Immunofluorescence results showed that cTnT expression in the 5-aza+salB+CLM group was stronger than other groups. Real-time qPCR and Western blotting analyses showed that cTnT, alpha-cardiac actin, mef-2c, Cx43, and GSK-3beta expression increased while beta-catenin expression decreased. The salB+5-aza+CLM group had the most evident effects. SalB combined with 5-aza and CLM improved cardiomyocyte differentiation from MSCs. In the MSCs differentiation process, the Wnt/beta-catenin signaling pathway had been inhibited.

scholarly journals Bie Jia Jian pill enhances the amelioration of bone mesenchymal stem cells on hepatocellular carcinoma progression

2021 ◽  
Author(s):  
Huang Jingjing ◽  
Huang Hongna ◽  
Wang Xiaojiao ◽  
Guo Yan ◽  
Zhong Yuexue ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protective Effect ◽  
Signal Pathway ◽  
Bone Mesenchymal Stem Cells ◽  
Alizarin Red ◽  
Huh7 Cells ◽  
Cancer Tissues

Abstract Background The therapeutic efficiency of Traditional Chinese Medicine (TCM) in suppressing the recurrence and metastasis of hepatocellular carcinoma (HCC) has been well proved. Objective The aim of this study is to investigate the role of Bie Jia Jian pill (BJJP) combined with bone mesenchymal stem cells (BMSCs) in HCC progression. Methods Flow cytometry was used to identify BMSCs isolated from BALB/c mice. The expressions of biomarkers and apoptosis rate of cancer stem cells (CSCs) enriched from Huh7 cells were also measured. The osteogenic differentiation and adipogenic differentiation ability of isolated BMSCs was determined by oil red O staining and Alizarin Red Staining. CSCs were used to establish the orthotopic HCC model. Histological changes in the liver tissues were examined by hematoxylin–eosin (H&E) staining and Van Gieson (VG) staining. The cell apoptotic rate in the cancer tissues was detected by TUNEL staining. The cell proliferation antigen Ki67 in the cancer tissues were detected by immunofluorescence assay and PCR, respectively. The levels of CSCs cellular surface markers (CD24, CD133 and EpCAM) and Wnt/β-catenin signal pathway related proteins were detected by PCR and western blot. Results Treatment of BJJP or BMSCs both improved the morphology induced by HCC and suppressed the differentiation ability of CSCs, as evidenced by down-regulated expressions of CD24, CD133, EpCAM and Ki67. The protective effect of BJJP or BMSCs in cancer tissues can be enhanced by the combination of BJJP and BMSCs. In addition to that, BJJP or BMSCs alone was found to increase the expression of miR-140 and promote cell apoptosis in CSCs, while down-regulation of miR-140 partially reversed the protective effect of BMSCs or BJJP + BMSCs on cancer tissues. BJJP + BMSCs treatment together also can down-regulate the expressions of Wnt3a and β-catenin. Conclusions These results proved the inhibitory role of BJJP + BMSCs in HCC development through regulating miR-140 and Wnt/β-catenin signal pathway.

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