Wnt/β-catenin signaling regulates neuronal differentiation of mesenchymal stem cells

Q, Yu; Liu, Lizhen; Duan, Yanping; Wang, Yan; Xuan, Xiaobo; Zhou, Liping; Liu, Wei

doi:10.1016/j.bbrc.2013.08.030

Cited by 20 publications

(20 citation statements)

References 24 publications

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“…Besides, bone marrow-derived mesenchymal stem cells have also been differentiated and studied, with the purpose of checking their multipotency as well as for being used as in vitro model for studying neurodegenerative disease [11]. The in vitro neuronal differentiation of bone marrow-derived MSCs is accomplished using various combinations of neurogenic inducers like retinoic acid, b-FGF and, β-ME [12]. Retinoic acid (RA), a vitamin A-derivative, facilitates neuronal differentiation of MSCs under appropriate cellular conditions [13].…”

Section: Introductionmentioning

confidence: 99%

A Simple Method for Isolation, Propagation, Characterization, and Differentiation of Adult Mouse Bone Marrow-Derived Multipotent Mesenchymal Stem Cells

Chaudhary¹,

Rath²

2016

J Cell Sci Ther

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Mesenchymal stem cells (MSCs) are spindle-shaped, adherent, clonogenic, non-phagocytic, fibroblastic and multipotent in nature with the intrinsic ability of self-renewal and proliferation. Bone marrow is the richest source of MSCs for studying the underlying processes of proliferation, self-renewal, and multiple-lineage differentiation. There have been several studies to improve the method of isolation, propagation, characterization and differentiation of mesenchymal stem cells from the mouse bone marrow, but none are widely acceptable. Owing to unavailability of universally acceptable method of MSCs culture continuous efforts are being made in this direction. Here, we report a simple method with some subtle modifications aiming to improve the overall method of isolation, culture, propagation and differentiation of MSCs in vitro. Following this protocol, we have isolated MSCs with typical spindle-shaped morphology as shown by scanning electron microscopy. These cells also showed expression of MSC-specific markers, CD29 (98.94% ± 0.67%), CD44 (84.27% ± 7.77%), Sca-1 (92.70% ± 3.81%) with negligible expression of HSC-specific markers such as CD45 (0.40% ± 0.10%), CD34 (0.15% ± 0.05%) and CD11b (0.45% ± 0.15%). MSCs were also found to differentiate into mesodermal lineages such as adipocytes, osteocytes and chondrocytes as well as ectodermal neuron-like cells. Moreover, MSCs showed differential basal expression of pluripotency-associated transcription factors such as Oct4, Nanog, Sox2 and Myc. Based on the above findings, we propose a simple protocol that can be used to isolate, culture, propagate and characterize multipotent MSCs from mouse bone marrow for experimental and application purposes.

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Section: Introductionmentioning

confidence: 99%

A Simple Method for Isolation, Propagation, Characterization, and Differentiation of Adult Mouse Bone Marrow-Derived Multipotent Mesenchymal Stem Cells

Chaudhary¹,

Rath²

2016

J Cell Sci Ther

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“…This stabilises β -catenin, which then translocates to the nucleus where it interacts with T-cell factor/lymphoid enhancer factor-1 to promote the transcription of target genes crucial for cell proliferation, stem cell self-renewal 7, 8 and cellular differentiation. 9 In the non-canonical Wnt/Ca 2+ pathway, the stimulation of FZD receptors in turn activates phospholipase C via G protein, which leads to an increase in the levels of intracellular Ca 2+ and activates protein kinase C, as well as the calcium/calmodulin-dependent kinase II. Deregulation of this non-canonical Wnt/Ca 2+ pathway has been implicated to drive cytoskeleton rearrangements, cellular motility, cellular proliferation and epithelial–mesenchymal (Mes) transition during cancer progression.…”

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confidence: 99%

FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway

et al. 2014

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Ovarian cancer (OC) can be classified into five biologically distinct molecular subgroups: epithelial-A (Epi-A), Epi-B, mesenchymal (Mes), Stem-A and Stem-B. Among them, Stem-A expresses genes relating to stemness and is correlated with poor clinical prognosis. In this study, we show that frizzled family receptor 7 (FZD7), a receptor for Wnt signalling, is overexpressed in the Stem-A subgroup. To elucidate the functional roles of FZD7, we used an RNA interference gene knockdown approach in three Stem-A cell lines: CH1, PA1 and OV-17R. Si-FZD7 OC cells showed reduced cell proliferation with an increase in the G0/G1 sub-population, with no effect on apoptosis. The cells also displayed a distinctive morphologic change by colony compaction to become more epithelial-like and polarised with smaller internuclear distances and increased z-axis height. Immunofluorescence (IF) staining patterns of pan-cadherin and β-catenin suggested an increase in cadherin-based cell–cell adhesion in si-FZD7 cells. We also observed a significant rearrangement in the actin cytoskeleton and an increase in tensile contractility in si-FZD7 OC cells, as evident by the loss of stress fibres and the redistribution of phospho-myosin light chain (pMLC) from the sites of cell–cell contacts to the periphery of cell colonies. Furthermore, there was reciprocal regulation of RhoA (Ras homolog family member A) and Rac1 (Ras-related C3 botulinum toxin substrate 1 (Rho family, small GTP-binding protein Rac1)) activities upon FZD7 knockdown, with a significant reduction in RhoA activity and a concomitant upregulation in Rac1 activity. These changes in pMLC and RhoA, as well as the increased TopFlash reporter activities in si-FZD7 cells, suggested involvement of the non-canonical Wnt/planar cell polarity (PCP) pathway. Selected PCP pathway genes (cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3), prickle homolog 4 (Drosophila) (PRICKLE4), dishevelled-associated activator of morphogenesis 1 (DAAM1), profilin 2 (PFN2), protocadherin 9 (PCDH9), protocadherin α1 (PCDHA1), protocadherin β17 pseudogene (PCDHB17), protocadherin β3 (PCDHB3), sprouty homolog 1 (SPRY1) and protein tyrosine kinase 7 (PTK7)) were found to be more highly expressed in Stem-A than non Stem-A subgroup of OC. Taken together, our results suggest that FZD7 might drive aggressiveness in Stem-A OC by regulating cell proliferation, cell cycle progression, maintenance of the Mes phenotype and cell migration via casein kinase 1ɛ-mediated non-canonical Wnt/PCP pathway.

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“…Spinal cord macrophages remove cellular debris at the site of injury, but their over activation can lead to neurotoxicity. ED1 is a marker whose expression level is proportional to the degree of activation of microglia and macrophages (Yu et al, ). In the present study, the area of ED1 expression around the injury site was lower in the BMSCs‐ and USW‐treated rats compared to controls 7 weeks post‐SCI (Fig.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow stromal cells transplantation combined with ultrashortwave therapy promotes functional recovery on spinal cord injury in rats

Yin

Lü

Zhang

et al. 2015

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This study investigated the effects of bone marrow stromal cells (BMSCs) transplantation combined with low dose ultrashortwave (USW) radiation on functional recovery from spinal cord injury (SCI) in rats. Female Sprague-Dawley rats (n = 64) were randomly divided into five groups: sham-operated, as well as control, USW, BMSCs, and BMSCs + USW that were subjected to spinal cord contusion. BMSCs were transplanted into rats in the BMSCs and BMSCs+USW groups, while those in the USW and BMSCs + USW were exposed to radiation; Basso-Beattie-Bresnahan (BBB) tests were performed before the operation and at 1-week intervals after SCI for 7 weeks. 7 weeks later, animals were assessed footprint pattern, motor evoked potential (MEP), histological features, and expression of the ED1 and glial fibrillary acidic protein (GFAP), markers of activated macrophages and astrocytes, respectively, in the lesion area. BBB scores were higher in the BMSCs + USW than in the BMSCs and control groups. The USW and BMSCs + USW groups had improved coordination compared to the BMSCs and control groups (P < 0.01 and P < 0.001, respectively, vs. control). BMSCs + USW rats had a lower ratio of lesion/cavity to spinal cord area than the other injured rats, and also had expression of GFAP in transplanted BMSCs. All treatment groups had lower ED1 expression and MEP latency than the controls (P < 0.01 and P < 0.001, respectively). The results indicate that BMSCs transplantation combined with USW radiation is more effective than either treatment alone in promoting functional recovery after SCI, possibly due to concomitant suppression of inflammation and spinal cord repair.

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Wnt/β-catenin signaling regulates neuronal differentiation of mesenchymal stem cells

Cited by 20 publications

References 24 publications

A Simple Method for Isolation, Propagation, Characterization, and Differentiation of Adult Mouse Bone Marrow-Derived Multipotent Mesenchymal Stem Cells

A Simple Method for Isolation, Propagation, Characterization, and Differentiation of Adult Mouse Bone Marrow-Derived Multipotent Mesenchymal Stem Cells

FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway

Bone marrow stromal cells transplantation combined with ultrashortwave therapy promotes functional recovery on spinal cord injury in rats

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