scholarly journals MANF Produced by MRL Mouse-Derived Mesenchymal Stem Cells Is Pro-regenerative and Protects From Osteoarthritis

2021 ◽  
Vol 9 ◽  
Author(s):  
Gautier Tejedor ◽  
Patricia Luz-Crawford ◽  
Audrey Barthelaix ◽  
Karine Toupet ◽  
Sébastien Roudières ◽  
...  
Keyword(s):  
Shotgun Proteomics ◽  
Key Factors ◽  
Major Step ◽  
Differentiation Potential ◽  
Scratch Wound ◽  
Migration Potential ◽  
And Migration ◽  
Interfering Rna ◽  
Mrl Mouse ◽  
Proliferation And Migration

The super healer Murphy Roths Large (MRL) mouse represents the “holy grail” of mammalian regenerative model to decipher the key mechanisms that underlies regeneration in mammals. At a time when mesenchymal stem cell (MSC)-based therapy represents the most promising approach to treat degenerative diseases such as osteoarthritis (OA), identification of key factors responsible for the regenerative potential of MSC derived from MRL mouse would be a major step forward for regenerative medicine. In the present study, we assessed and compared MSC derived from MRL (MRL MSC) and C57BL/6 (BL6 MSC) mice. First, we compare the phenotype and the differentiation potential of MRL and BL6 MSC and did not observe any difference. Then, we evaluated the proliferation and migration potential of the cells and found that while MRL MSC proliferate at a slower rate than BL6 MSC, they migrate at a significantly higher rate. This higher migration potential is mediated, in part, by MRL MSC-secreted products since MRL MSC conditioned medium that contains a complex of released factors significantly increased the migration potential of BL6 MSC. A comparative analysis of the secretome by quantitative shotgun proteomics and Western blotting revealed that MRL MSC produce and release higher levels of mesencephalic astrocyte-derived neurotrophic factor (MANF) as compared to MSC derived from BL6, BALB/c, and DBA1 mice. MANF knockdown in MRL MSC using a specific small interfering RNA (siRNA) reduced both MRL MSC migration potential in scratch wound assay and their regenerative potential in the ear punch model in BL6 mice. Finally, injection of MRL MSC silenced for MANF did not protect mice from OA development. In conclusion, our results evidence that the enhanced regenerative potential and protection from OA of MRL mice might be, in part, attributed to their MSC, an effective reservoir of MANF.

scholarly journals The Histone Demethylase KDM3B Promotes Osteo-/Odontogenic Differentiation, Cell Proliferation, and Migration Potential of Stem Cells from the Apical Papilla

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Chen Zhang ◽  
Xiao Han ◽  
Yuncun Liang ◽  
Huina Liu ◽  
Zhipeng Fan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Histone Demethylase ◽  
Alp Activity ◽  
Cell Proliferation And Migration ◽  
Odontogenic Differentiation ◽  
Migration Potential ◽  
Apical Papilla ◽  
And Migration ◽  
Proliferation And Migration

Understanding the regulation mechanisms of mesenchymal stem cells (MSCs) can assist in tissue regeneration. The histone demethylase (KDM) family has a crucial role in differentiation and cell proliferation of MSCs, while the function of KDM3B in MSCs is not well understood. In this study, we used the stem cells from the apical papilla (SCAPs) to test whether KDM3B could regulate the function of MSCs. By an alkaline phosphatase (ALP) activity assay, Alizarin red staining, real-time RT-PCR, and western blot analysis, we found that KDM3B enhanced the ALP activity and mineralization of SCAPs and promoted the expression of runt-related transcription factor 2 (RUNX2), osterix (OSX), dentin sialophosphoprotein (DSPP), and osteocalcin (OCN). Additionally, the CFSE, CCK-8, and flow cytometry assays revealed that KDM3B improved cell proliferation by accelerating cell cycle transition from the G1 to S phase. Scratch and transwell migration assays displayed that KDM3B promoted the migration potential of SCAPs. Mechanically, microarray results displayed that 98 genes were upregulated, including STAT1, CCND1, and FGF5, and 48 genes were downregulated after KDM3B overexpression. Besides, we found that the Toll-like receptor and JAK-STAT signaling pathway may be involved in the regulating function of KDM3B in SCAPs. In brief, we discovered that KDM3B promoted the osteo-/odontogenic differentiation, cell proliferation, and migration potential of SCAPs and provided a novel target and theoretical basis for regenerative medicine.

scholarly journals Biological Characteristics of Umbilical Cord Mesenchymal Stem Cells and Its Therapeutic Potential for Hematological Disorders

2021 ◽  
Vol 9 ◽  
Author(s):  
Yufeng Shang ◽  
Haotong Guan ◽  
Fuling Zhou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Therapeutic Potential ◽  
Biological Characteristics ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Hematological Disorders ◽  
And Migration ◽  
Proliferation And Migration

Umbilical cord mesenchymal stem cells (UC-MSCs) are a class of multifunctional stem cells isolated and cultured from umbilical cord. They possessed the characteristics of highly self-renewal, multi-directional differentiation potential and low immunogenicity. Its application in the field of tissue engineering and gene therapy has achieved a series of results. Recent studies have confirmed their characteristics of inhibiting tumor cell proliferation and migration to nest of cancer. The ability of UC-MSCs to support hematopoietic microenvironment and suppress immune system suggests that they can improve engraftment after hematopoietic stem cell transplantation, which shows great potential in treatment of hematologic diseases. This review will focus on the latest advances in biological characteristics and mechanism of UC-MSCs in treatment of hematological diseases.

PPP2R3A Affects the Function and Mechanism of Heterogeneous Fibroblasts in Pulmonary Fibrosis

2021 ◽  
Author(s):  
Xiaoni Shi ◽  
Shaoqi Yang ◽  
Wei Luo ◽  
Sha Wang ◽  
Jie Huang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Physiological Saline ◽  
Cell Counting ◽  
Lesion Area ◽  
And Migration ◽  
Remodeling Of Extracellular Matrix ◽  
Interfering Rna ◽  
Tgf Β1 ◽  
Proliferation And Migration

Abstract Background: Fibroblasts have important roles in the synthesis and remodeling of extracellular matrix (ECM) proteins during pulmonary fibrosis. However, the spatiotemporal distribution of heterogeneous fibroblasts during disease progression remains unknown. Methods: Physiological saline and silica were used to generate a chronic pulmonary fibrosis model in mice, and single-cell sequencing, spatial transcriptome sequencing, real-time fluorescent quantitative PCR, immunohistochemistry and immunofluorescence were performed to identify fibroblast subtypes. Small interfering RNA was used to specifically knockdown the target protein, and western blotting, bromodeoxyuridine (BrdU), Cell Counting Kit-8 (CCK-8) and wound healing assays were used to detect the role of GREM1/PPP2R3A in a newly identified fibroblast subtype. Results: Fibroblasts of the new subtype were mainly located in the lesion area and coexpressed inflammation- and proliferation-related genes; they were termed inflammatory-proliferation fibroblasts. Grem1 was the most highly expressed gene in this subtype, as confirmed in HPF-a cells after TGF-β1 treatment. We characterized the downstream mechanism of GREM1/PPP2R3A: these factors mediated the increases in cell viability, proliferation and migration induced by TGF-β1 in fibroblasts. Conclusion: This new subtype of inflammatory, proliferative fibroblasts plays a pivotal role during pulmonary fibrosis, and PPP2R3A, as a downstream regulatory target of GREM1, is involved in pulmonary fibrosis, providing new insights for the prevention and treatment of silicosis.

Tenascin-C regulates proliferation and migration of cultured astrocytes in a scratch wound assay

Neuroscience ◽  
2005 ◽  
Vol 132 (1) ◽  
pp. 87-102 ◽  
Author(s):  
T. Nishio ◽  
S. Kawaguchi ◽  
M. Yamamoto ◽  
T. Iseda ◽  
T. Kawasaki ◽  
...  
Keyword(s):  
Tenascin C ◽  
Cultured Astrocytes ◽  
Scratch Wound ◽  
Scratch Wound Assay ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Human Glioblastoma-Derived Mesenchymal Stem Cell to Pericytes Transition and Angiogenic Capacity in Glioblastoma Microenvironment

2018 ◽  
Vol 46 (1) ◽  
pp. 279-290 ◽  
Author(s):  
Dongye Yi ◽  
Wei Xiang ◽  
Qing Zhang ◽  
Yongcun Cen ◽  
Qing Su ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Blue Staining ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
And Migration ◽  
Proliferation And Migration ◽  
Vascular Formation

Background/Aims: Tumor vascular formation and maintenance are crucial events in glioblastoma development. Mesenchymal stem cells (MSCs) have been shown to differentiate into pericytes and contribute to neovascularization in the glioma microenvironment. Moreover, glioblastoma-derived mesenchymal stem cells (gb-MSCs), which consist of CD90-MSCs and CD90+MSCs, are a subpopulation of MSCs that are more active in glioma vascularization. However, the functions of gb-MSCs and the microRNA (miRNA) modifications in the glioblastoma microenvironment have not yet been fully elucidated. Here, we focus on the pericyte differentiation potential of gb-MSCs and miRNA modifications in gb-MSCs during new vascular formation and glioblastoma growth. Methods: In vitro, surface markers of gb-MSCs were detected by flow cytometry; the differentiation potential was evaluated by Oil Red O staining, Alizarin Red staining and Alcian blue staining; the proliferation and migration of gb-MSCs in different conditioned media were analyzed by the cck8 test and wound-healing assay, respectively; gb-MSC to pericyte transition was detected by immunofluorescence staining and western blot assay; angiogenetic capacity was analyzed by tube formation assay; and levels of cytokines in different supernatant were determined by ELISA. Additionally, RNA was isolated from gb-MSCs, and miRNA modifications were analyzed using the RAffymetrix miRNA microarray Results: We showed that glioblastoma-conditioned medium increased gb-MSC proliferation and migration and was capable of inducing gb-MSC differentiation into pericytes. Glioblastoma secreted angiogenic factors and gb-MSCs incubated in malignant glioblastoma-conditioned medium formed more tube-like structures, and these cells also adhered to tube-like vessels formed by human umbilical vein endothelial cells (HUVECs) on Matrigel to maintain tumor vascular structure in vitro. miRNA expression were also modified in gb-MSCs cultured in malignant glioblastoma-conditioned medium in vitro. Conclusion: These results provide new insight into the functional effects of a subpopulation of MSCs in glioblastoma and may help in the development of novel therapies for solid tumors.

Sign in / Sign up

Export Citation Format

Share Document