Co-transplantation of bone marrow mesenchymal stem cells and monocytes in the brain stem to repair the facial nerve axotomy

After the facial nerve axotomy (FNA), the distal end of the axon would gradually decay and disappear. Accumulated evidence shows that transplantation of bone marrow mesenchymal stem cells (BMSCs) reveals potential in the treatment of nervous system diseases or injuries. This study is aimed at investigating the therapeutic effects of co-transplantation of BMSCs and monocytes in FNA. We found that co-culture significantly elevated the CD4+/CD8+ ratio and CD4+ CD25+ T cell proportion compared with monocytes transplantation, and enhanced the differentiation of BMSCs into neurons. After the cell transplantation, the lowest apoptosis in the facial nerve nucleus was found in the co-transplantation group 2 (BMSCs:monocytes= 1:30). Moreover, the lowest expression levels of pro-inflammatory cytokines and the highest expression levels of anti-inflammatory cytokines were observed in the co-transplantation group 2 (BMSCs: monocytes= 1:30). The highest expression levels of protein in the JAK/STAT6 pathway and the SDF-1/CXCR4 axis were found in the co-transplantation group 2. BMSC/monocyte co-transplantation significantly improves the microenvironment in the facial nerve nucleus in FNA rats; therefore these findings suggest that it could promote the anti-/pro-inflammatory balance shift towards the anti-inflammatory microenvironment, alleviating survival conditions for BMSCs, regulating BMSC the chemotaxis homing, differentiation, and the section of BMSCs, and finally reducing the neuronal apoptosis. These findings might provide essential evidence for the in-hospital treatment of FNA with co-transplantation of BMSCs and monocytes.

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The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-019-1512-3 ◽

2019 ◽

Vol 14 (1) ◽

Author(s):

Bin Zhao ◽

Gengyan Xing ◽

Aiyuan Wang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Signaling Pathway ◽

Adipogenic Differentiation ◽

Osteoblastic Differentiation ◽

Bmp Signaling ◽

Blank Group ◽

Expression Levels ◽

Marrow Mesenchymal Stem Cells

Abstract Background This study was conducted with the aim of exploring the effect of the BMP signaling pathway on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (rBMSCs) in rats with osteoporosis (OP). Methods The bilateral ovaries of female SD rats were resected for the establishment of a rat OP model. The osteoblastic differentiation of isolated rBMSCs was identified through osteogenic induction. Adipogenetic induction and flow cytometry (FCM) were used to detect adipogenic differentiation and the expression of rBMSC surface markers. The rBMSCs were grouped into the blank group, NC group, si-BMP2 group, and oe-BMP2 group. The expression levels of key factors and osteogenesis-related factors were determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The formation of calcified nodules was observed by alizarin red staining. ALP activity was measured by alkaline phosphatase staining. Results The rats with OP had greater weight but decreased bone mineral density (BMD) than normal rats (all P < 0.01). The rBMSCs from rats with OP were capable of osteoblastic differentiation and adipogenic differentiation and showed high expression of CD44 (91.3 ± 2.9%) and CD105 (94.8 ± 2.1%). Compared with the blank group, the oe-BMP2 group had elevated BMP-2 and Smad1 levels and an increase in calcified nodules and ALP-positive staining areas (all P < 0.05). Moreover, the expression levels of Runx2, OC, and OPN in the oe-BMP2 group were relatively higher than those in the blank group (all P < 0.05). The findings in the si-BMP2 group were opposite to those in the oe-BMP2 group. Conclusion BMP signaling pathways activated by BMP-2 can promote the osteoblastic differentiation of rBMSCs from rats with OP.

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Suppression of Clonogenic Potential of Human Bone Marrow Mesenchymal Stem Cells by HIV Type 1: Putative Role of HIV Type 1 Tat Protein and Inflammatory Cytokines

AIDS Research and Human Retroviruses ◽

10.1089/088922202760265597 ◽

2002 ◽

Vol 18 (13) ◽

pp. 917-931 ◽

Cited By ~ 23

Author(s):

Lixin Wang ◽

Debasis Mondal ◽

Vincent F. La Russa ◽

Krishna C. Agrawal

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Inflammatory Cytokines ◽

Tat Protein ◽

Marrow Mesenchymal Stem Cells ◽

Clonogenic Potential ◽

Hiv Type 1

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Mechano growth factor E peptide regulates migration and differentiation of bone marrow mesenchymal stem cells

Journal of Molecular Endocrinology ◽

10.1530/jme-13-0157 ◽

2013 ◽

Vol 52 (2) ◽

pp. 111-120 ◽

Cited By ~ 25

Author(s):

Hanwei Cui ◽

Qian Yi ◽

Jianguo Feng ◽

Li Yang ◽

Liling Tang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Adipogenic Differentiation ◽

Expression Levels ◽

Migration Effect ◽

Mechano Growth Factor ◽

Marrow Mesenchymal Stem Cells ◽

Igf1 Receptor

IGF1Ec in humans or IGF1Eb in rodents (known as mechano growth factor (MGF)) has a unique E domain, and the C-terminal end of the E domain (MGF E peptide) plays important roles in proliferation, migration and differentiation of many cell types. Bone marrow mesenchymal stem cells (BMSCs) have multiple differentiation potentials and are considered as perfect seed cells for tissue repair. But the role of MGF E peptide on BMSCs is seldom investigated and the mechanism is still unclear. In this study, we investigated the effects of MGF E peptide on rat BMSCs (rBMSCs). Our results revealed that treatment with MGF E peptide had no effect on BMSC proliferation. However, both wound-healing and transwell assays indicated that MGF E peptide could significantly enhance rBMSCs migration ability. Further analysis indicated that MGF E peptide also reduced the expression levels of osteogenic genes, but increased the expression levels of adipogenic genes. Analysis of molecular mechanism showed that phosphorylation-Erk1/2 was activated by MGF E peptide and blockage of either Erk1/2 or IGF1 receptor could repress the migration effect of MGF E peptide. In conclusion, MGF E peptide is able to inhibit osteogenic differentiation but promote adipogenic differentiation. In addition, the migration effect of MGF E peptide on rBMSCs depends on IGF1 receptor via Erk1/2 signal pathway.

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Bone Morphogenetic Protein-7 (BMP-7) Promotes Neuronal Differentiation of Bone Marrow Mesenchymal Stem Cells (BMSCs) In Vitro

BioMed Research International ◽

10.1155/2021/7239783 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Heng Zhang ◽

Wen Zhang ◽

Guangchao Bai ◽

Lei Gao ◽

Kuanxin Li

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Morphogenetic Protein ◽

Bone Morphogenetic Protein 7 ◽

Expression Levels ◽

Cell Protrusion ◽

Morphogenetic Protein ◽

Marrow Mesenchymal Stem Cells

This study is aimed at investigating the effects of bone morphogenetic protein-7 (BMP-7) on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neuron-like cells in vitro. The rat BMSCs were isolated and identified, which were divided into the control, empty, recombinant rhBMP-7 transfection, and Lv-BMP-7 transfection groups. BMSCs were induced under different conditions. CCK-8 assay was performed to detect cell proliferation. ALP was used to detect cell activity. Cellular morphology after induction was observed. Immunofluorescence was conducted to detect the expression and location of nerve cell markers. Quantitative real-time PCR and Western blot analysis were performed to detect the mRNA and protein expression levels, respectively. The rhBMP-7 and Lv-BMP-7 promoted the proliferation of BMSCs, accompanied with increased ALP activities. Morphological observations revealed that rhBMP-7 and Lv-BMP-7 induced BMSCs to differentiate into neuron-like cells. Immunofluorescence revealed that the rhBMP-7 and Lv-BMP-7 groups showed positive expression of MAP-2 and Nfh in BMSCs. MAP-2 was mainly distributed in the cell body and cellular protrusion, while Nfh was mainly distributed in the cytoplasm and cell protrusion. Positive mRNA and protein expressions of MAP-2 and Nfh were observed in the cells of the rhBMP-7 and Lv-BMP-7 groups, and the expression levels were significantly higher than the control and empty groups. Both exogenous BMP-7 (rhBMP-7) and endogenous BMP-7 (Lv-BMP-7) can induce BMSCs to differentiate into neuron-like cells highly expressing the neuronal markers MAP-2 and Nfh.

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Inhibition of PPARγ Gene Particle Downregulates the Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells into Adipocytes

Scientific Programming ◽

10.1155/2021/5335241 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Yi Dong ◽

Long Chang ◽

Long Hei ◽

Sensen Yang ◽

Wenxin Ma ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Fatty Acid ◽

Control Group ◽

Expression Levels ◽

Triacylglycerol Content ◽

Marrow Mesenchymal Stem Cells ◽

Rabbit Bone ◽

Pparγ Gene

This study aims to evaluate the effect of peroxisome proliferator-activated receptor (PPAR) γ gene inhibition on the adipogenic differentiation of rabbit bone marrow mesenchymal stem cells (BMSCs). Primary BMSCs were isolated from rabbit bone marrow, cultured, and the markers of BMSCs on cell’s surface were analyzed using flow cytometry. The experiment involved five groups, namely, control: untreated BMSCs; model: BMSCs treated with ethanol; empty siRNA: BMSCs treated with ethanol + empty siRNA; PPARγ: BMSCs treated with ethanol + PPARγ siRNA; and PPARγ inhibitor: BMSCs treated with ethanol + T0070907. RT-PCR and Western blotting were used to detect changes in the expression level of PPARγ, PETALA2 (AP2), lipoprotein lipase (LPL), fatty acid transport protein (FATP) 1, and fatty acid transporter (FAT). Adipocyte count and triacylglycerol content of the model and the empty siRNA groups were considerably greater than the control group ( P < 0.01 ). After the inhibition with PPARγ or T0070907, adipocyte count and triacylglycerol content of the PPARγ and T0070907 groups were significantly reduced ( P < 0.01 ), with no statistically significantly difference than the control group ( P > 0.05 ). The expression levels of PPARγ gene and protein in the model and empty siRNA groups were ominously enhanced than the control group ( P < 0.01 ), and after inhibition with PPARγ or T0070907, the PPARγ gene or protein expression level of PPARγ and T0070907 groups significantly reduced ( P < 0.01 ), with no statistically significance difference compared to the control group ( P > 0.05 ). The expression levels of Ap2, LPL, FATP1, and FAT genes in the model and empty siRNA groups were considerably greater compared to the control group ( P < 0.01 ). Inhibition with PPARγ or T0070907 in the PPARγ and T0070907 groups, respectively, lead to significantly reduced expression levels of adipogenic genes ( P < 0.01 ), with no statistically significance difference compared to the control ( P > 0.05 ). Inhibition of PPARγ gene downregulates the differentiation of BMSCs into adipocytes, indicating its putative role in the expression of adipogenic genes.

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Knockdown of has_circ_0010452 Promotes Proliferation and Osteogenic Differentiation via Up-Regulating miR-543 in Human Bone Marrow Mesenchymal Stem Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2966 ◽

2022 ◽

Vol 12 (4) ◽

pp. 770-777

Author(s):

Siyuan Chen ◽

Weixiong Guo ◽

Jinsong Wei ◽

Han Lin ◽

Fengyan Guo

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Human Bone ◽

Human Bone Marrow ◽

Cell Counting ◽

Luciferase Reporter ◽

Expression Levels ◽

Marrow Mesenchymal Stem Cells

Objective: The aim of this study was to explore the role of has_circ_0010452 in the progression of osteoporosis (OP) targeting miR-543, as well as their functions in regulating proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Methods: The expression levels of circ_0010452 and miR-543 in hBMSCs at different time points of osteogenic differentiation were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After transfection of circ_0010452 siRNA or miR-543 inhibitor in hBMSCs, the relative expression levels of osteogenic marker proteins, including oat spelt xylan (OSX), osteocalcin (OCN) and collagen I (Col-1), were determined by western blot. Cell proliferation of hBMSCs was valued by Cell Counting Kit 8 (CCK-8) assay. Dual-Luciferase reporter gene assay was performed to verify the relationship between circ_0010452 and miR-543. Subsequently, the regulatory effects of circ_0010452 and miR-543 on osteogenic differentiation and the capability of mineralization were evaluated by alkaline phosphatase (ALP) determination and alizarin red staining, respectively. Results: The expression of circ_0010452 decreased gradually and miR-543 increased in hBMSCs with the prolongation of osteogenic differentiation. circ_0010452 could bind to miR-543, which was negatively regulated by miR-543 in hBMSCs. Moreover, knockdown of circ_0010452 inhibited proliferation and osteogenic differentiation by upregulating miR-543, as well as upregulating expressions of OSX, OCN and Col-1. Furthermore, knockdown of circ_0010452 markedly promoted the capability of mineralization of hBMSCs, which was further reversed by transfection of miR-543 inhibitor. The knockdown of miR-543 partially reversed the inhibitory effect of circ_0010452 on the osteogenesis of hBMSCs. Conclusions: Silence of circ_0010452 promotes the development of OP via binding to miR-543 regulating proliferation and osteogenic differentiation of hBMSCs, thus promoting the progression of osteoporosis.

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dlk1/FA1 Regulates the Function of Human Bone Marrow Mesenchymal Stem Cells by Modulating Gene Expression of Pro-inflammatory Cytokines and Immune Response-related Factors

Journal of Biological Chemistry ◽

10.1074/jbc.m607530200 ◽

2006 ◽

Vol 282 (10) ◽

pp. 7339-7351 ◽

Cited By ~ 64

Author(s):

Basem M. Abdallah ◽

Patrice Boissy ◽

Qihua Tan ◽

Jesper Dahlgaard ◽

Gunnhildur A. Traustadottir ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Bone Marrow ◽

Immune Response ◽

Mesenchymal Stem Cells ◽

Inflammatory Cytokines ◽

Human Bone ◽

Related Factors ◽

Marrow Mesenchymal Stem Cells ◽

Pro Inflammatory Cytokines

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Enhanced Proliferation of Porcine Bone Marrow Mesenchymal Stem Cells Induced by Extracellular Calcium is Associated with the Activation of the Calcium-Sensing Receptor and ERK Signaling Pathway

Stem Cells International ◽

10.1155/2016/6570671 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Jingjing Ye ◽

Wei Ai ◽

Fenglin Zhang ◽

Xiaotong Zhu ◽

Gang Shu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Signaling Pathway ◽

Extracellular Calcium ◽

Phase Cell ◽

Calcium Sensing Receptor ◽

Expression Levels ◽

Calcium Sensing ◽

Marrow Mesenchymal Stem Cells

Porcine bone marrow mesenchymal stem cells (pBMSCs) have the potential for application in regenerative medicine. This study aims to investigate the effects of extracellular calcium (Ca2+o) on pBMSCs proliferation and to explore the possible underlying mechanisms. The results demonstrated that 4 mMCa2+osignificantly promoted pBMSCs proliferation by reducing the G0/G1 phase cell percentage and by increasing the S phase cell proportion and the proliferation index of pBMSCs. Accordingly,Ca2+ostimulated the expression levels of proliferative genes such as cyclin A2, cyclin D1/3, cyclin E2, and PCNA and inhibited the expression of p21. In addition,Ca2+oresulted in a significant elevation of intracellular calcium and an increased ratio of p-ERK/ERK. However, inhibition of calcium-sensing receptor (CaSR) by its antagonist NPS2143 abolished the aforementioned effects ofCa2+o. Moreover,Ca2+o-induced promotion of pBMSCs proliferation, the changes of proliferative genes expression levels, and the activation of ERK1/2 signaling pathway were effectively blocked by U0126, a selective ERK kinase inhibitor. In conclusion, our findings provided evidence that the enhanced pBMSCs proliferation in response toCa2+owas associated with the activation of CaSR and ERK1/2 signaling pathway, which may be useful for the application of pBMSCs in future clinical studies aimed at tissue regeneration and repair.

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