scholarly journals Hydroxyurea‐induced senescent peripheral blood mesenchymal stromal cells inhibit bystander cell proliferation of JAK2V617F‐positive human erythroleukemia cells

FEBS Journal ◽  
2019 ◽  
Vol 286 (18) ◽  
pp. 3647-3663 ◽  
Author(s):  
Sunčica Bjelica ◽  
Miloš Diklić ◽  
Dragoslava Đikić ◽  
Marijana Kovačić ◽  
Tijana Subotički ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Bystander Cell ◽  
Erythroleukemia Cells

scholarly journals High Mannose N-Glycans Promote Migration of Bone-Marrow-Derived Mesenchymal Stromal Cells

2020 ◽  
Vol 21 (19) ◽  
pp. 7194
Author(s):  
Vivian Alonso-Garcia ◽  
Cutter Chaboya ◽  
Qiongyu Li ◽  
Bryan Le ◽  
Timothy J. Congleton ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Percutaneous Injection ◽  
Secretion Profile ◽  
Migration Potential ◽  
High Mannose ◽  
Over Time

For hundreds of indications, mesenchymal stromal cells (MSCs) have not achieved the expected therapeutic efficacy due to an inability of the cells to reach target tissues. We show that inducing high mannose N-glycans either chemically, using the mannosidase I inhibitor Kifunensine, or genetically, using an shRNA to silence the expression of mannosidase I A1 (MAN1A1), strongly increases the motility of MSCs. We show that treatment of MSCs with Kifunensine increases cell migration toward bone fracture sites after percutaneous injection, and toward lungs after intravenous injection. Mechanistically, high mannose N-glycans reduce the contact area of cells with its substrate. Silencing MAN1A1 also makes cells softer, suggesting that an increase of high mannose N-glycoforms may change the physical properties of the cell membrane. To determine if treatment with Kifunensine is feasible for future clinical studies, we used mass spectrometry to analyze the N-glycan profile of MSCs over time and demonstrate that the effect of Kifunensine is both transitory and at the expense of specific N-glycoforms, including fucosylations. Finally, we also investigated the effect of Kifunensine on cell proliferation, differentiation, and the secretion profile of MSCs. Our results support the notion of inducing high mannose N-glycans in MSCs in order to enhance their migration potential.

Mesenchymal Stromal Cells from Female Donors Enhance Breast Cancer Cell Proliferation in vitro

Oncology ◽  
2015 ◽  
Vol 88 (4) ◽  
pp. 214-225 ◽  
Author(s):  
Ilkka Pasanen ◽  
Mika Pietilä ◽  
Siri Lehtonen ◽  
Elisa Lehtilahti ◽  
Tanja Hakkarainen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Proliferation In Vitro

Mesenchymal Stromal Cells with Immunosuppressive Potential Can Be Mobilized Into Peripheral Blood by Electro-Acupuncture

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4805-4805
Author(s):  
Lizhen Liu ◽  
Qin Yu ◽  
Shan Fu ◽  
Hui Dong ◽  
Kaimin Hu ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Haematopoietic Stem Cell ◽  
Adherent Cells ◽  
Sprague Dawley ◽  
T Lymphocyte Proliferation ◽  
Immunosuppressive Property ◽  
Tgf Β1

Abstract Abstract 4805 Background: Mesenchymal stromal cells (MSCs) constitute a population of multipotential cells giving rise to adipocytes, osteoblasts and chondrocytes. Combining with their engraftment promoting capacity and immunosuppressive property, MSCs may be therapeutically useful for haematopoietic stem cell transplantation. A small number of MSCs can be mobilized into circulation by appropriate stimuli, such as hypoxia. However, there is little evidence for clinically useful methods for MSC mobilization. In this study, we used animal model to determine whether MSCs can be mobilized into peripheral blood (PB) by electro-acupuncture (EA), a traditional Chinese medical method. Design and Methods: Adult male Sprague-Dawley rats (200–220g) were randomly divided into there groups: EA-7 days, EA-14 days and control groups. For EA treatment, the rats were immobilized. A pair of stainless needles of 0.35mm diameter was inserted into points ‘Jizhong’ (GV6) and ‘Mingmen’ (DU4) and was then connected with output terminals of an EA apparatus. Alternating strings of dense-sparse frequencies were selected and the intensity was adjusted to induce slight twitch of the skin, with the intensity lasting for 30 min. Electro-acupuncture was applied to rats once a day for 7days or 14days. The control rats were immobilized for the same period without EA. To quantify the number of MSCs and evaluate mobilization efficiency, PB and bone barrow (BM) samples of each group were collected and colony-forming unit fibroblast (CFU-F) assays were performed. Mobilized PB derived MSCs were identified by immunophenotype and trilineage differentiation. Mixed lymphocyte reactions (MLR) were done to evaluate the immunosuppressive potential of mobilized MSCs and the cytokine levels TGF-β1, HGF and IL-10 in the supernatants of MSCs culture were measured by ELISA. Results: We found that MSCs can be mobilized into PB by electro-acupuncture. CFU-F frequency in rat PB was significantly increased after electro-acupuncture for 7days (8.20 ±1.48 vs.1.40 ±0.55 CFU-Fs per 3×106 cells) (p<0.05, n=5). PB CFU-F frequency increased to 12.4±1.82 per 3×106 cells in rats treated with electro-acupuncture for 14 days. However, no significant differences were observed in BM CFU-Fs among varies groups (P>0.05). Mobilized PB derived adherent cells were positive for CD90, CD29 and CD44, but negative for CD34 and CD45. After adipogenic, osteogenic, and chondrogenic induction, adherent cells from mobilized PB were positive for specific stains. In addition, they expressed mRNAs of Lpl and Pparg2 (adipocytic markers), Bglap and Runx2 (osteoblastic markers), and Col2a1 and Col10a1 (chondrocytic markers). These results showed that mobilized PB-derived cells could differentiate into adipocyte, osteoblast, and chondrocyte, which indicated that they are bona fide MSCs. The levels of immunosuppressive cytokines TGF-β1, HGF and IL-10 in the supernatants of PB-MSC culture were similar as BM MSCs. Results of MLR showed that mobilized PB derived MSCs inhibited T lymphocyte proliferation. Conclusion: Taken together, these data revealed, for the first time to the best of our knowledge, that multipotential MSCs can be mobilized by electro-acupuncture. Our study provides a clinical useful method to mobilize MSCs with immunosuppressive potential and highlight a novel insight into the mechanisms of electro-acupuncture therapy. Disclosures: No relevant conflicts of interest to declare.

Mesenchymal Stromal Cells Enhance G-CSF-Induced Mobilization Of Hematopoietic Stem- and Progenitor Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2460-2460
Author(s):  
Evert-Jan F. M. de Kruijf ◽  
Ingmar van Hengel ◽  
Jorge M Perez-Galarza ◽  
Willem E. Fibbe ◽  
Melissa van Pel
Keyword(s):  
Bone Marrow ◽  
B Lymphocytes ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Bone Marrow Cells ◽  
Calf Serum ◽  
Intraperitoneal Administration ◽  
Hematopoietic Stem ◽  
Marrow Cells

Abstract Hematopoietic stem- and progenitor cell (HSPC) mobilization is a property of most hematopoietic growth factors, such as Granulocyte Colony Stimulating Factor (G-CSF). Not all donors mobilize equally well and therefore the number of HSPC that are obtained following mobilization may be limited. Mesenchymal stromal cells (MSC) have the capacity to differentiate into cells of the mesodermal lineage and have immunomodulatory properties in vivo and in vitro. Here, we have investigated the effect of MSC co-administration on G-CSF-induced HSPC mobilization. MSC were obtained from bone marrow cells (bone marrow-derived) or bone fragments (bone-derived) and were expanded in alpha-MEM containing 10% fetal calf serum until sufficient cell numbers were obtained. Bone marrow or bone-derived MSC were administered intravenously for three days at a dose of 200 x103 cells per day to male C57BL/6 recipients that were simultaneously mobilized with G-CSF (10 μg per day intraperitoneally for 3 days) or PBS as a control. Co-injection of G-CSF and MSC lead to a 2-fold increase in HSPC mobilization compared to G-CSF alone (8,563 ± 3,309 vs. 4,268 ± 1,314 CFU-C per ml peripheral blood respectively; n=13, p<0.01). Administration of MSC alone did not induce HSPC mobilization (273 ± 229 CFU-C/ml blood; n=13). Furthermore, co-injection of splenocytes and G-CSF did not enhance HSPC mobilization, showing that the administration of exogeneous cells as such is not sufficient for enhancement of HSPC mobilization. It has been reported that G-CSF-induced HSPC mobilization is associated with a decrease in the number of osteal macrophages, B lymphocytes and erythroid progenitors. Administration of MSC alone induced a significant decrease in the frequency of osteal macrophages (7.9 ± 1.2 vs 6.2 ± 1.4% bone marrow cells for PBS vs. MSC respectively; n=8, p<0.05), but did not affect osteoblast numbers. Furthermore, the frequency of B lymphocytes was significantly decreased following MSC administration (29.9 ± 4.0 vs. 16.5 ± 4.9% bone marrow cells for PBS vs. MSC respectively; n=13, p<0.0001). No differences were observed in erythroid numbers following MSC administration. To investigate the mechanisms underlying these observations, the migratory capacity of luciferase transduced MSC was studied through bioluminescence imaging. Following intravenous injection, MSC were detected in the lungs, but not in other organs. In addition, no difference in MSC migration was observed between G-CSF and PBS treated mice. Moreover, intraperitoneal administration of G-CSF and MSC resulted in increased HSPC mobilization compared to G-CSF alone (10,178 ±3,039 vs. 5,158 ± 2,436 CFU-C per ml peripheral blood; n=5-12). Together, these data point to an endocrine effect of MSC on G-CSF-induced HSPC mobilization. No differences in IL-6, CXCL-12 or M-CSF levels in bone marrow extracellular fluid were observed. In conclusion, G-CSF-induced HSPC mobilization is enhanced by injection of MSC. We hypothesize that the MSC-induced partial depletion of B lymphocytes and osteal macrophages in the bone marrow are crucial factors involved in the enhancement of G-CSF-induced HSPC mobilization. Disclosures: No relevant conflicts of interest to declare.

Culture and characterisation of equine peripheral blood mesenchymal stromal cells

2013 ◽  
Vol 195 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Jan H. Spaas ◽  
Catharina De Schauwer ◽  
Pieter Cornillie ◽  
Evelyne Meyer ◽  
Ann Van Soom ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Peripheral Blood

scholarly journals Inhibition of T-Cell Proliferation by Murine Multipotent Mesenchymal Stromal Cells is Mediated by CD39 Expression and Adenosine Generation

2011 ◽  
Vol 20 (8) ◽  
pp. 1221-1230 ◽  
Author(s):  
Christine Sattler ◽  
Manuela Steinsdoerfer ◽  
Monika Offers ◽  
Elke Fischer ◽  
Rudolf Schierl ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
T Cell Proliferation
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