Molecular mechanisms of migration and homing of intravenously transplanted mesenchymal stem cells

Холоденко, И. В.; Konieva, A. A.; Холоденко, Р. В.; Yarygin, K. N.

doi:10.7243/2050-1218-2-4

Cited by 42 publications

(27 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A prerequisite for these cells to participate in tissue repair is migration of injected MSCs to the damaged tissues [2]. When injected intravenously, MSCs appear to preferentially home to sites of injury [3], which has been observed in tissue injuries that occur in the bone [4], liver [5], brain [6], and heart [7].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro

et al. 2017

Stem Cell Res Ther

View full text Add to dashboard Cite

BackgroundMesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms.MethodsHuman bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence.ResultsHuman bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but not Losartan, indicating that FAK activation and F-actin reorganization were downstream of AT2R.ConclusionsThese data indicate that Ang II-AT2R regulates human bone marrow MSC migration by signaling through the FAK and RhoA/Cdc42 pathways. This study provides insights into the mechanisms by which MSCs home to injury sites and will enable the rational design of targeted therapies to improve MSC engraftment.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro

et al. 2017

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…It is noteworthy that at 7 days after infusion, the infused cells were mainly found in blood vessels, whereas only rare cells were located in the brain parenchyma. Many rMSCs in blood vessels had a fusiform shape and tended to adhere to the wall of the vessel, suggesting a cell attempt to transmigrate into the parenchyma [61]. Accordingly, at 28 days after infusion, the great majority of rMSCs were found in the brain parenchyma.…”

Section: Resultsmentioning

confidence: 99%

Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral Effects

Cerri

Greco

Levandis

et al. 2015

Stem Cells Translational Medicine

View full text Add to dashboard Cite

This study demonstrates that mesenchymal stem cells infused through the carotid artery do not efficiently cross the blood-brain barrier in rats with a Parkinson's disease-like degeneration of nigrostriatal neurons, unless a permeabilizing agent (e.g., mannitol) is used. The infusion did not reduce the neuronal damage and associated motor impairment, but abolished the motor abnormalities these animals typically show when challenged with a dopaminergic agonist. Therefore, although arterially infused mesenchymal stem cells did not show neurorestorative effects in this study's Parkinson's disease model, they appeared to normalize the pathological responsiveness of striatal neurons to dopaminergic stimulation. This capability should be further explored in future studies.

show abstract

“…Similarities between the wound-healing process and tumour stroma formation have led to the suggestion that tumours are 'wounds that do not heal' (Dvorak 1986). We and others have shown that MSCs are actively recruited to growing tumour stroma (Conrad et al 2007, Zischek et al 2009, Knoop et al 2011, Knoop et al 2013) mediated by high local concentrations of inflammatory chemokines and growth factors (Ponte et al 2007, Spaeth et al 2008, Kholodenko et al 2013. This tumour tropism constitutes the basis for the 'Trojan horse' approach, in which MSCs are used as shuttle vectors to deliver therapeutic agents into growing tumours , Dwyer et al 2011, Dembinski et al 2013, Zhu et al 2014, Zhang et al 2015, as we have successfully demonstrated in our previous work using the sodium iodide symporter (NIS) (Knoop et al 2011, Knoop et al 2013 and herpes simplex virus type 1 thymidine kinase (HSV-TK) (Zischek et al 2009 as therapy genes in various tumour models.…”

Section: Introductionmentioning

confidence: 99%

Thyroid hormones and tetrac: new regulators of tumour stroma formation via integrin αvβ3

Schmohl¹,

Müller²,

Wechselberger³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

To improve our understanding of non-genomic, integrin avb3-mediated thyroid hormone action in tumour stroma formation, we examined the effects of triiodo-L-thyronine (T 3 ), L-thyroxine (T 4 ) and integrin-specific inhibitor tetrac on differentiation, migration and invasion of mesenchymal stem cells (MSCs) that are an integral part of the tumour's fibrovascular network. Primary human bone marrow-derived MSCs were treated with T 3 or T 4 in the presence of hepatocellular carcinoma (HCC) cell-conditioned medium (CM), which resulted in stimulation of the expression of genes associated with cancer-associated fibroblast-like differentiation as determined by qPCR and ELISA. In addition, T 3 and T 4 increased migration of MSCs towards HCC cell-CM and invasion into the centre of three-dimensional HCC cell spheroids. All these effects were tetrac-dependent and therefore integrin avb3-mediated. In a subcutaneous HCC xenograft model, MSCs showed significantly increased recruitment and invasion into tumours of hyperthyroid mice compared to euthyroid and, in particular, hypothyroid mice, while treatment with tetrac almost completely eliminated MSC recruitment. These studies significantly improve our understanding of the anti-tumour activity of tetrac, as well as the mechanisms that regulate MSC differentiation and recruitment in the context of tumour stroma formation, as an important prerequisite for the utilisation of MSCs as gene delivery vehicles.

show abstract

Molecular mechanisms of migration and homing of intravenously transplanted mesenchymal stem cells

Cited by 42 publications

References 92 publications

RETRACTED ARTICLE: Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro

RETRACTED ARTICLE: Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro

Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral Effects

Thyroid hormones and tetrac: new regulators of tumour stroma formation via integrin αvβ3

Contact Info

Product

Resources

About