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 ◽  
...  

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.

2016 ◽  
Vol 610 ◽  
pp. 6-12 ◽  
Author(s):  
Wipawan Thangnipon ◽  
Nicha Puangmalai ◽  
Nirut Suwanna ◽  
Rungtip Soi-ampornkul ◽  
Ruchee Phonchai ◽  
...  

2009 ◽  
Vol 17 ◽  
pp. S260
Author(s):  
G.T. Heldens ◽  
E.L. Vitters ◽  
O.J. Arntz ◽  
S. Veenbergen ◽  
M.B. Bennink ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Chongxiao Chen ◽  
Roshan Adhikari ◽  
Dima Lynn White ◽  
Woo Kyun Kim

1,25-dihydroxyvitamin D3 (1,25OHD) has been suggested to play an important role in osteogenic differentiation and mineralization. However, limited data have been reported in avian species. In the present study, the direct role of 1,25OHD on osteogenic differentiation and mineralization in chicken mesenchymal stem cells (cMSCs) derived from day-old broiler bones was investigated. cMSCs were treated with control media (C), osteogenesis media (OM), OM with 1, 5, 10, and 50 nM 1,25OHD, respectively. The messenger RNA (mRNA) samples were obtained at 24 and 48 h and 3 and 7 days to examine mRNA expression of key osteogenic genes [runt related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), collagen type I alpha 2 chain (COL1A2), bone gamma-carboxyglutamate protein (BGLAP), secreted phosphoprotein 1 (SPP1), and alkaline phosphatase (ALP)]. Cells were stained at 7, 14, and 21 days using Von Kossa (mineralization), Alizarin Red (AR; mineralization), and Alkaline Phosphatase (early marker) staining methods. From the mRNA expression results, we found a time-dependent manner of 1,25OHD on osteoblast differentiation and mineralization. In general, it showed an inhibitory effect on differentiation and mineralization during the early stage (24 and 48 h), and a stimulatory effect during the late cell stage (3 and 7 days). The staining showed 1,25OHD had an inhibitory effect on ALP enzyme activities and mineralization in a dosage-dependent manner up to 14 days. However, at 21 days, there was no difference between the treatments. This study provides a novel understanding of the effects of 1,25OHD on osteogenic differentiation and mineralization of cMSCs depending on cell stage and maturity.


Author(s):  
Nguyen Thu Huyen ◽  
Duong Minh Chau ◽  
Do Thi Xuan Phuong ◽  
Nguyen Thanh Liem ◽  
Than Thi Trang Uyen

Extracellular vesicles (EVs) are emerging as a potential candidate for disease treatment due to their bioactive cargoes. Recently, mesenchymal stem cells (MSC)-derived EVs have shown their capacity to replace parental cells as their similar functions to MSCs. The therapeutic effects of EVs depend on their cargo, such as DNA, miRNA, proteins, and lipids. In this study, we expanded umbilical cord-derived MSCs (UCMSCs) for EV release. Additionally, we evaluated the expression level of several microRNAs in three EV populations, including apoptotic bodies (AB), microvesicles (MV), and exosomes (EX). Results showed that UCMSCs released three EV types: AB, MV, and EX into culture media. The three EV populations were different in morphology and size. Three EVs were detected to carry microRNAs, such as hsa-miR-320, hsa-miR-181b, and hsa-miR-140. Among these microRNAs, hsa-miR-140 expressed with the greatest level, followed by hsa-miR-181b and hsa-miR-320. The results of this study provide more knowledge about UCMSC-derived EV miRNAs in addition to reveal the potential role of UCMSC-EVs associated with detected miRNAs.


Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1327-1333 ◽  
Author(s):  
Grazia Maria Spaggiari ◽  
Andrea Capobianco ◽  
Heba Abdelrazik ◽  
Flavio Becchetti ◽  
Maria Cristina Mingari ◽  
...  

Abstract Recently, a number of clinical trials used either mesenchymal stem cells (MSCs) or natural killer (NK) cells in an attempt to improve the effectiveness of hematopoietic stem cell transplantation (HSCT). In view of the relevant role of both MSCs and NK cells in HSCT, we have recently explored the result of possible interactions between the 2 cell types. We found that activated NK cells could kill MSCs, whereas MSCs strongly inhibited interleukin-2 (IL-2)–induced NK-cell proliferation. In this study, we further analyzed the inhibitory effect exerted by MSCs on NK cells. We show that MSCs not only inhibit the cytokine-induced proliferation of freshly isolated NK cells but also prevent the induction of effector functions, such as cytotoxic activity and cytokine production. Moreover, we show that this inhibitory effect is related to a sharp down-regulation of the surface expression of the activating NK receptors NKp30, NKp44, and NKG2D. Finally, we demonstrate that indoleamine 2,3-dioxygenase and prostaglandin E2 represent key mediators of the MSC-induced inhibition of NK cells.


2019 ◽  
Vol 20 (2) ◽  
pp. 345 ◽  
Author(s):  
Stefano Martellucci ◽  
Costantino Santacroce ◽  
Francesca Santilli ◽  
Luca Piccoli ◽  
Simona Delle Monache ◽  
...  

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.


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