Mesenchymal stem cells transfected with anti-miRNA-204-3p inhibit acute rejection after heart transplantation by targeting C-X-C motif chemokine receptor 4 (CXCR4) in vitro

Abstract Bone marrow–derived mesenchymal stem cells (BM-MSCs) are stromal cells with the ability to proliferate and differentiate into many tissues. Although they represent powerful tools for several therapeutic settings, mechanisms regulating their migration to peripheral tissues are still unknown. Here, we report chemokine receptor expression on human BM-MSCs and their role in mediating migration to tissues. A minority of BM-MSCs (2% to 25%) expressed a restricted set of chemokine receptors (CXC receptor 4 [CXCR4], CX3C receptor 1 [CX3CR1], CXCR6, CC chemokine receptor 1 [CCR1], CCR7) and, accordingly, showed appreciable chemotactic migration in response to the chemokines CXC ligand 12 (CXCL12), CX3CL1, CXCL16, CC chemokine ligand 3 (CCL3), and CCL19. Using human pancreatic islets as an in vitro model of peripheral tissue, we showed that islet supernatants released factors able to attract BM-MSCs in vitro, and this attraction was principally mediated by CX3CL1 and CXCL12. Moreover, cells with features of BM-MSCs were detected within the pancreatic islets of mice injected with green fluorescent protein (GFP)–positive BM. A population of bona fide MSCs that also expressed CXCR4, CXCR6, CCR1, and CCR7 could be isolated from normal adult human pancreas. This study defines the chemokine receptor repertoire of human BM-MSCs that determines their migratory activity. Modulation of homing capacity may be instrumental for harnessing the therapeutic potential of BM-MSCs.

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Preconditioning of Hypoxic Culture Increases The Therapeutic Potential of Adipose Derived Mesenchymal Stem Cells

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2021.5870 ◽

2021 ◽

Vol 9 (F) ◽

pp. 505-515

Author(s):

Tito Sumarwoto ◽

Heri Suroto ◽

Ferdiansyah Mahyudin ◽

Dwikora Novembri Utomo ◽

Romaniyanto Romaniyanto ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factors ◽

Chemokine Receptor ◽

Therapeutic Potential ◽

Trophic Factors ◽

Receptor Type ◽

Angiogenic Growth Factors ◽

Hypoxic Precondition

Various in vitro preconditioning strategies have been implemented to increase the regenerative capacity of MSCs. Among them are modulation of culture atmosphere (hypoxia or anoxia), three-dimensional culture (3D), addition of trophic factors (in the form of growth factors, cytokines or hormones), lipopolysaccharides, and pharmacological agents. Preconditioning mesenchymal stem cells by culturing them in a hypoxic environment, which resembles the natural oxygen environment of the tissues (1% –7%) and not with standard culture conditions (21%), increases the survival of these cells via Hypoxia Inducible Factor-1α (HIF-1a) and via Akt-dependent mechanisms. In addition, the hypoxic precondition stimulates the secretion of pro-angiogenic growth factors, increases the expression of chemokines SDF-1 (stromal cell-derived factor-1) and its receptor CXCR4 (chemokine receptor type 4) - CXCR7 (chemokine receptor type 7) and increases engraftment of stem cell. This review aims to provide an overview of the preconditioned hypoxic treatment to increase the therapeutic potential of adipose-derived mesenchymal stem cells.

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Immunomodulatory effects of mesenchymal stem cells for the treatment of cardiac allograft rejection

Experimental Biology and Medicine ◽

10.1177/1535370220978650 ◽

2020 ◽

pp. 153537022097865

Author(s):

Zhichao Wu ◽

Jialiang Liang ◽

Wei Huang ◽

Lin Jiang ◽

Christian Paul ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Heart Transplantation ◽

Broad Spectrum ◽

Allograft Rejection ◽

Cardiac Allograft ◽

Survival Prognosis ◽

Cardiac Allograft Rejection

Heart transplantation continues to be the gold standard clinical intervention to treat patients with end-stage heart failure. However, there are major complications associated with this surgical procedure that reduce the survival prognosis of heart transplant patients, including allograft rejection, malignancies, infections, and other complications that arise from the use of broad-spectrum immunosuppression drugs. Recent studies have demonstrated the use of mesenchymal stem cells (MSCs) against allotransplantation rejection in both in vitro and in vivo settings due to their immunomodulatory properties. Therefore, utilization of MSCs provides new and exciting strategies to improve heart transplantation and potentially reduce the use of broad-spectrum immunosuppression drugs while alleviating allograft rejection. In this review, we will discuss the current research on the mechanisms of cardiac allograft rejection, the physiological and immunological characteristics of MSCs, the effects of MSCs on the immune system, and immunomodulation of heart transplantation by MSCs.

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Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Molecular Biology of the Cell ◽

10.1091/mbc.e07-02-0166 ◽

2007 ◽

Vol 18 (8) ◽

pp. 2873-2882 ◽

Cited By ~ 168

Author(s):

James E. Ip ◽

Yaojiong Wu ◽

Jing Huang ◽

Lunan Zhang ◽

Richard E. Pratt ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Chemokine Receptor ◽

Cytokine Receptors ◽

Integrin Β1 ◽

Cxc Chemokine Receptor 4 ◽

Cxc Chemokine ◽

Integrin Α4 ◽

And Migration ◽

Chemokine Receptor 4

Recent evidence has demonstrated the importance of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the repair of damaged myocardium. The molecular mechanisms of engraftment and migration of BM-MSCs in the ischemic myocardium are unknown. In this study, we developed a functional genomics approach toward the identification of mediators of engraftment and migration of BM-MSCs within the ischemic myocardium. Our strategy involves microarray profiling (>22,000 probes) of ischemic hearts, complemented by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting of corresponding adhesion molecule and cytokine receptors in BM-MSCs to focus on the coexpressed pairs only. Our data revealed nine complementary adhesion molecules and cytokine receptors, including integrin β1, integrin α4, and CXC chemokine receptor 4 (CXCR4). To examine their functional contributions, we first blocked selectively these receptors by preincubation of BM-MSCs with specific neutralizing antibodies, and then we administered these cells intramyocardially. A significant reduction in the total number of BM-MSC in the infarcted myocardium was observed after integrin β1 blockade but not integrin α4 or CXCR4 blockade. The latter observation is distinctively different from that reported for hematopoietic stem cells (HSCs). Thus, our data show that BM-MSCs use a different pathway from HSCs for intramyocardial trafficking and engraftment.

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