Human mesenchymal stem cells are recruited to injured liver in a β1-integrin and CD44 dependent manner

Hepatology ◽  
2012 ◽  
Vol 56 (3) ◽  
pp. 1063-1073 ◽  
Author(s):  
Victoria Aldridge ◽  
Abhilok Garg ◽  
Nicholas Davies ◽  
David C. Bartlett ◽  
Janine Youster ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Β1 Integrin ◽  
Dependent Manner ◽  
Injured Liver

scholarly journals P85 Human mesenchymal stem cells bind preferentially to injured liver in a  1-integrin and CD44 dependent manner

Gut ◽  
2011 ◽  
Vol 60 (Suppl 2) ◽  
pp. A39-A39
Author(s):  
V. Aldridge ◽  
N. Davies ◽  
J. Youster ◽  
D. Kavanagh ◽  
N. Kalia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Dependent Manner ◽  
Injured Liver

Integrin β1 activation by micro-scale curvature promotes pro-angiogenic secretion of human mesenchymal stem cells

2017 ◽  
Vol 5 (35) ◽  
pp. 7415-7425 ◽  
Author(s):  
Zhengdong Li ◽  
Weiwei Wang ◽  
Xun Xu ◽  
Karl Kratz ◽  
Jie Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Β1 Integrin ◽  
Integrin Β1 ◽  
Micro Scale ◽  
Culture Substrate ◽  
A Cell ◽  
Scale Surface ◽  
Cell Culture Substrate

A cell culture substrate with micro-scale surface curvature promotes β1 integrin activation and pro-angiogenic secretion of mesenchymal stem cells.

scholarly journals Effect of Human Mesenchymal Stem Cells on Xenogeneic T and B Cells Isolated from Lupus-Prone MRL.Faslpr Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hong Kyung Lee ◽  
Eun Young Kim ◽  
Hyung Sook Kim ◽  
Eun Jae Park ◽  
Hye Jin Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Human Mesenchymal Stem Cells ◽  
Preclinical Studies ◽  
Dependent Manner ◽  
T And B Cells

Systemic lupus erythematosus (SLE) is an autoimmune disease, which is characterized by hyperactivation of T and B cells. Human mesenchymal stem cells (hMSCs) ameliorate the progression of SLE in preclinical studies using lupus-prone MRL.Faslpr mice. However, whether hMSCs inhibit the functions of xenogeneic mouse T and B cells is not clear. To address this issue, we examined the in vitro effects of hMSCs on T and B cells isolated from MRL.Faslpr mice. Naïve hMSCs inhibited the functions of T cells but not B cells. hMSCs preconditioned with IFN-γ (i) inhibited the proliferation of and IgM production by B cells, (ii) attracted B cells for cell–cell interactions in a CXCL10-dependent manner, and (iii) inhibited B cells by producing indoleamine 2,3-dioxygenase. In summary, our data demonstrate that hMSCs exert therapeutic activity in mice in three steps: first, naïve hMSCs inhibit the functions of T cells, hMSCs are then activated by IFN-γ, and finally, they inhibit B cells.

scholarly journals Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sonali Rawat ◽  
Vatsla Dadhwal ◽  
Sujata Mohanty
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Tissue Specific ◽  
Immunomodulatory Property ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory ◽  
Basic Characteristics

Abstract Background Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their immunosuppressive, anti-inflammatory and regenerative potentials. Belonging to a glucocorticoid family, Dexamethasone (Dex) is a powerful anti-inflammatory compound that is widely used as therapy in autoimmune disease conditions or allogeneic transplantation. However, minimal immunomodulatory effect of hMSCs may limit their therapeutic uses. Moreover, the effect of glucocorticoids on the immunomodulatory molecules or other regenerative properties of tissue-specific hMSCs remains unknown. Method Herein, we evaluated the in vitro effect of Dex at various dose concentrations and time intervals, 1000 ng/ml, 2000 ng/ml, 3000 ng/ml and 24 h, 48 h respectively, on the basic characteristics and immunomodulatory properties of Bone marrow derived MSC (BM-MSCs), Adipose tissue derived MSCs (AD-MSCs), Dental Pulp derived MSC (DP-MSCs) and Umbilical cord derived MSCs (UC-MSCs). Results The present study indicated that the concentration of Dex did not ramify the cellular morphology nor showed cytotoxicity as well as conserved the basic characteristics of tissue specific hMSCs including cell proliferation and surface marker profiling. However, quite interestingly it was observed that the stemness markers (Oct-4, Sox-2, Nanog and Klf-4) showed a significant upregulation in DP-MSCs and AD-MSCs followed by UC-MSCs and BM-MSCs. Additionally, immunomodulatory molecules, Prostaglandin E-2 (PGE-2), Indoleamine- 2,3-dioxygenase (IDO) and Human Leukocyte Antigen-G (HLA-G) were seen to be upregulated in a dose-dependent manner. Moreover, there was a differential response of tissue specific hMSCs after pre-conditioning with Dex during mixed lymphocyte reaction, wherein UC-MSCs and DP-MSCs showed enhanced immunosuppression as compared to AD-MSCs and BM-MSCs, thereby proving to be a better candidate for therapeutic applications in immune-related diseases. Conclusion Dex preconditioning improved the hMSCs immunomodulatory property and may have reduced the challenge associated with minimal potency and strengthen their therapeutic efficacy. Graphical Abstract Preconditioning of tissue specific hMSCs with dexamethasone biomanufacturers the enhanced potential hMSCs with better stemness and immunomodulatory properties for future therapeutics.

scholarly journals 15-Deoxy-Δ12,14-Prostaglandin J2Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Xin Liu ◽  
Shuangshuang Jia ◽  
Weiyang Li ◽  
Le Yang ◽  
Lin Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Chronic Liver ◽  
Dependent Manner ◽  
Ros Production ◽  
Repressive Effect ◽  
Primary Mouse ◽  
Injured Liver

It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) have capacity to migrate to the damaged liver and contribute to fibrogenesis in chronic liver diseases. 15-Deoxy-Δ12,14-prostaglandin J2(15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARγ), is considered a new inhibitor of cell migration. However, the actions of 15d-PGJ2on BMSC migration remain unknown. In this study, we investigated the effects of 15d-PGJ2on the migration of BMSCs using a mouse model of chronic liver fibrosis and primary mouse BMSCs. Our results demonstrated thatin vivo, 15d-PGJ2administration inhibited the homing of BMSCs to injured liver by flow cytometric analysis and,in vitro, 15d-PGJ2suppressed primary BMSC migration in a dose-dependent manner determined by Boyden chamber assay. Furthermore, the repressive effect of 15d-PGJ2was blocked by reactive oxygen species (ROS) inhibitor, but not PPARγantagonist, and action of 15d-PGJ2was not reproduced by PPARγsynthetic ligands. In addition, 15d-PGJ2triggered a significant ROS production and cytoskeletal remodeling in BMSCs. In conclusion, our results suggest that 15d-PGJ2plays a crucial role in homing of BMSCs to the injured liver dependent on ROS production, independently of PPARγ, which may represent a new strategy in the treatment of liver fibrosis.

Bacterial Endotoxin LPS but Not LTA Can Enhance Osteogenic Differentiation of Human Mesenchymal Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4230-4230
Author(s):  
Godfrey ChiFung Chan ◽  
F.Y. Mo ◽  
K.H.K. Yip ◽  
J. Li ◽  
H. Law ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oral Cavity ◽  
Osteogenic Differentiation ◽  
Culture Condition ◽  
Human Mesenchymal Stem Cells ◽  
Human Mscs ◽  
Dependent Manner ◽  
Alp Activity ◽  
Dose Dependent

Abstract Background & Objective: Dental implant requires osseointegration for anchoring and human’s oral cavity has plenty of bacterial oral flora. Whether these bacteria have any effects on the human mesenchymal Stem Cells (MSCs) that can differentiate into osteoblasts remains unknown. We therefore investigated the effect of bacterial endotoxins commonly found in the oral cavity and gastrointestinal tract, namely lipopolysaccharides (LPS, Escherichia coli) and lipoteichoic acid (LTA, Streptococcus pyogenes), on the proliferation and osteogenic differentiation of MSCs. Methods: Human MSCs are derived from bone marrow (BM) of normal healthy donors. The culture condition, immunophenotyping determination and tests of differentiating functions of the human MSCs were similar to what we reported previously (Li J, Br J Haematol 2004). The proliferation of MSCs under either a 3-day or a prolonged 7-day endotoxins challenge was evaluated by XTT assay. The extent of osteogenic differentiation was examined under microscopy and measured by the increase in alkaline phosphatase (ALP) activity at day 10 and the calcium mineralization/deposition per unit volume of protein at day 14. Results: There was no significant effect of LPS and LTA on the growth and proliferation of MSCs, even under a relatively high dose. However, continued LPS challenge on MSCs under osteogenic culture condition was shown to increase the ALP activity and calcium deposition in a dose-dependent manner (100ng/ml, 1 ug/ml, 10ug/ml). No such phenomenon can be identified when LTA challenge was used. Conclusions: LPS and LTA did not show any significant effect on the proliferation and growth of human MSCs. However, LPS enhanced the osteogenic differentiation of MSCs in a dose-dependent manner. Our finding suggests that the endotoxin from bacteria commonly found in the oral cavity and gut does not have any negative impact on MSCs induced osteogenesis.

scholarly journals Discovery of chemerin as the new chemoattractant of human mesenchymal stem cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Irene Kim ◽  
Hyomin Park ◽  
Injoo Hwang ◽  
Dodam Moon ◽  
Hyunji Yun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Transendothelial Migration ◽  
Target Organ ◽  
Target Tissue ◽  
Cmv Promoter ◽  
Migration Assay ◽  
Cloned Gene ◽  
Injured Liver

Abstract Background The homing capacity of human mesenchymal stem cells (hMSCs) to the injured sites enables systemic administration of hMSCs in clinical practice. In reality, only a small proportion of MSCs are detected in the target tissue, which is a major bottleneck for MSC-based therapies. We still don’t know the mechanism how MSCs are chemo-attracted to certain target organ and engrafted through trans-endothelial migration. In this study, we aimed to determine the mechanism how the circulating hMSCs home to the injured liver. Methods and results When we compare the cytokine array between normal and injured mouse liver at 1-day thioacetamide (TAA)-treatment, we found that chemerin, CXCL2, and CXCL10 were higher in the injured liver than normal one. Among three, only chemerin was the chemoattractant of hMSCs in 2D- and 3D-migration assay. Analysis of the signal transduction pathways in hMSCs showed that chemerin activated the phosphorylation of JNK1/2, ERK1/2 and p38, and finally upregulated CD44, ITGA4, and MMP-2 that are involved in the transendothelial migration and extravasation of MSCs. Upstream transcription regulators of CD44, ITGA4, and MMP-2 after chemerin treatment were MZF1, GATA3, STAT3, and STAT5A. To develop chemerin as a chemoattractant tool, we cloned gene encoding the active chemerin under the CMV promoter (CMV-aChemerin). We analyzed the migration of hMSCs in the 3D model for space of the Disse, which mimics transmigration of hMSCs in the liver. CMV-aChemerin-transfected hepatocytes were more effective to attract hMSC than control hepatocytes, leading to the enhanced transendothelial migration and homing of hMSCs to liver. The homing efficiency of the intravascularly-delivered hMSCs to liver was evaluated after systemic introduction of the CMV-aChemerin plasmid packed in liposome-vitamin A conjugates which target liver. CMV-aChemerin plasmid targeting liver significantly enhanced homing efficiency of hMSCs to liver compared with control plasmid vector. Conclusions Chemerin is the newly found chemoattractant of hMSCs and may be a useful tool to manipulate the homing of the intravascularly-administered hMSC to the specific target organ.

scholarly journals Dexamethasone Priming Enhances Stemness and Immunomodulatory Property of Tissue-specific Human Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Sonali Rawat ◽  
Vatsla Dadhwal ◽  
Sujata Mohanty
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Tissue Specific ◽  
Immunomodulatory Property ◽  
Cell Based Therapy ◽  
Anti Inflammatory ◽  
Basic Characteristics

Abstract Background: Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their immunosuppressive, anti-inflammatory and regenerative potentials. Belonging to a glucocorticoid family, Dexamethasone (Dex) is a powerful anti-inflammatory compound that is widely used as therapy in autoimmune disease conditions or allogeneic transplantation. However, minimal immunomodulatory effect of hMSCs may limit their therapeutic uses. Moreover, the effect of glucocorticoids on the immunomodulatory molecules or other regenerative properties of tissue-specific hMSCs remains unknown. Method: Herein, we evaluated the in vitro effect of Dex at various dose concentrations and time intervals, 1000 ng/ml, 2000 ng/ml, 3000 ng/ml and 24 h, 48 h respectively, on the basic characteristics and immunomodulatory properties of Bone marrow derived MSC (BM-MSCs), Adipose tissue derived MSCs (AD-MSCs), Dental Pulp derived MSC (DP-MSCs) and Umbilical cord derived MSCs (UC-MSCs). Results: The present study indicated that the concentration of Dex did not ramify the cellular morphology nor showed cytotoxicity as well as conserved the basic characteristics of tissue specific hMSCs including cell proliferation and surface marker profiling. However, quite interestingly it was observed that the stemness markers (Oct-4, Sox-2, Nanog & Klf-4) showed a significant upregulation in DP-MSCs and AD-MSCs followed by UC-MSCs and BM-MSCs. Additionally, immunomodulatory molecules, Prostaglandin E-2 (PGE-2), Indoleamine- 2,3-dioxygenase (IDO) and Human Leukocyte Antigen-G (HLA-G) were seen to be upregulated in a dose-dependent manner. Moreover, there was a differential response of tissue specific hMSCs after pre-conditioning with Dex during mixed lymphocyte reaction, wherein UC-MSCs and DP-MSCs showed enhanced immunosuppression as compared to AD-MSCs and BM-MSCs, thereby proving to be a better candidate for therapeutic applications in immune-related diseases. Conclusion: Dex preconditioning ameliorates the hMSCs immunomodulatory property and may void the challenge associated with minimal potency and strengthen their therapeutic efficacy.

Sign in / Sign up

Export Citation Format

Share Document