A comprehensive characterization study of human bone marrow mscs with an emphasis on molecular and ultrastructural properties

2011 ◽  
Vol 226 (5) ◽  
pp. 1367-1382 ◽  
Author(s):  
Erdal Karaöz ◽  
Alparslan Okçu ◽  
Gülçin Gacar ◽  
Özlem Sağlam ◽  
Sinan Yürüker ◽  
...  
2017 ◽  
Vol 17 (3) ◽  
pp. 1771-1778 ◽  
Author(s):  
Sarah Abuelreich ◽  
Muthurangan Manikandan ◽  
Abdullah Aldahmash ◽  
Musaad Alfayez ◽  
Mohammed Fayez Al Rez ◽  
...  

Biomaterials ◽  
2012 ◽  
Vol 33 (29) ◽  
pp. 6998-7007 ◽  
Author(s):  
Yunqing Kang ◽  
Sungwoo Kim ◽  
Julius Bishop ◽  
Ali Khademhosseini ◽  
Yunzhi Yang

2020 ◽  
Author(s):  
Jin Qi ◽  
Ruihao Zhang ◽  
Zuolong Wu ◽  
Yayi Xia

Abstract Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can release a large number of exosomes which act as paracrine mediators in tumor associated microenvironment. However, the role of MSC-derived exosomes in pathogenesis and progression of cancer cells especially osteosarcoma has not yet been thoroughly clarified until now. In this study, we established a co-culture model for human bone marrow derived MSCs with osteosarcoma U2OS and MG63 cells, then extraction of exosomes from induced MSCs and study the role of MSC-derived exosomes in the progression of osteosarcoma cell. It was the aim of this study to address potential cell biological effects between MSCs and osteosarcoma cell. we found that MSC-derived exosomes can significantly promote osteosarcoma cells proliferation and invasion. we also found that miR-21-5p were significantly overexpressed in human bone marrow MSCs and MSC-derived exosomes compared with that of human fetal osteoblastic cell line hFOB1.19 by using quantitative realtime polymerase chain reaction (qRT-PCR). Proliferation and invasion of osteosarcoma cells U2OS and MG63 were significantly enhanced by MSC-derived exosomes that were transfected with miR-21-5p. Bioinformatics analysis and dual‐luciferase reporter gene assays validated the targeted relationship between exosomal miR‐21-5p and PIK3R1. Furthermore, we demonstrated that miR-21-5p-abundant exosomes derived human bone marrow MSCs could activate PI3K/Akt/mTOR pathway by suppressing PIK3R1 expression in osteosarcoma cells U2OS and MG63. In conclusion, Our findings provide new insight into the interaction between MSCs and osteosarcoma cells in tumor associated microenvironment. Notably, the use of a miR-21-5p inhibitor has an excellent restraining effect on osteosarcoma proliferation and invasion, which provides therapeutic potential for osteosarcoma in future clinical medicine.


2017 ◽  
Vol 9 (3) ◽  
pp. 999-1015 ◽  
Author(s):  
Kalyan K. Pasumarthy ◽  
Naresh Doni Jayavelu ◽  
Lotta Kilpinen ◽  
Colin Andrus ◽  
Stephanie L. Battle ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Katsunori Shiraishi ◽  
Naosuke Kamei ◽  
Shunsuke Takeuchi ◽  
Shinobu Yanada ◽  
Hisashi Mera ◽  
...  

Quality evaluation of mesenchymal stem cells (MSCs) based on efficacy would be helpful for their clinical application. In this study, we aimed to find the factors of human bone marrow MSCs relating to cartilage repair. The expression profiles of humoral factors, messenger RNAs (mRNAs), and microRNAs (miRNAs) were analyzed in human bone marrow MSCs from five different donors. We investigated the correlations of these expression profiles with the capacity of the MSCs for proliferation, chondrogenic differentiation, and cartilage repair in vivo. The mRNA expression of MYBL1 was positively correlated with proliferation and cartilage differentiation. By contrast, the mRNA expression of RCAN2 and the protein expression of TIMP-1 and VEGF were negatively correlated with proliferation and cartilage differentiation. However, MSCs from all five donors had the capacity to promote cartilage repair in vivo regardless of their capacity for proliferation and cartilage differentiation. The mRNA expression of HLA-DRB1 was positively correlated with cartilage repair in vivo. Meanwhile, the mRNA expression of TMEM155 and expression of miR-486-3p, miR-148b, miR-93, and miR-320B were negatively correlated with cartilage repair. The expression analysis of these factors might help to predict the ability of bone marrow MSCs to promote cartilage repair.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 774-774 ◽  
Author(s):  
Pratibha Singh ◽  
Seiji Fukuda ◽  
Mary R. Saunders ◽  
Louis M. Pelus

Mesenchymal stemcells (MSCs) are found throughout adult organisms and are involved in tissue maintenance and repair, as well as in the regulation of hematopoiesis and immunologic responses. Several clinical trials are currently under way to use allogeneic MSCs for enhancement of hematopoietic stem cell transplantation and treatment of graft-versus-host disease, spinal cord injury, cartilage and meniscus repair, and stroke. However, the therapeutic uses of MSCs can be limited by insufficient MSC number, their survival, and their ability to differentiate into multiple lineages, pointing to an important need to identify factors regulating MSC survival, proliferation, and differentiation. In this study, we explored the role of the anti-apototic protein Survivin in MSC functions. Survivin is an intracellular member of the inhibitor-of-apoptosis protein (IAP) family and is implicated in regulation of apoptosis, cell division, and cell cycle control of many cell types including hematopoietic stem cells, leukemic cells, and endothelial cells. However, whether Survivin is involved in MSC activity or function is unknown. Using flow cytometry and function assays, we found that adult mouse and human MSCs, identified as CD45-Ter119-CD51+PDGFR+Nestin+ cells, express high levels of Survivin, which regulates MSCs survival and expansion under normal physiological and stressful conditions. Flow cytometry analysis revealed that approximately 40.5±3.6% of mouse bone marrow MSCs, 33.6±4.2% of adult human bone marrow MSCs, and 43.6±5.3% human cord blood MSCs express Survivin. Treatment of mice in vivo with YM155 (10 mg/kg), a small molecule Survivin inhibitor, for 6 days decreased bone marrow CD45-Ter119-CD51+PDGFR+Nestin+ MSC by 2.1 fold and functional fibroblast colony formation (CFU-F) by 2.8 fold. Survivin gene deletion using Survivin-specific SiRNA decreased mouse and human bone marrow derived MSCs number and CFU-F ability by 3.2 fold and 2.8 fold respectively. Retroviral overexpression of Survivin in mouse MSCs enhanced CFU-F formation by 4 fold. In an in vitro wound healing assay YM155-treated MSCs recovered more slowly compared to control cultures. To determine underlying mechanisms involved in Survivin dependent regulation of MSC function, we measured the survival and proliferation of YM155 treated MSCs. Treatment of mouse or human bone marrow-derived MSCs with YM155 (50 nmol/l) for 48 hours enhanced the caspase 3 and 7 expression by 42.8% and 63.9% respectively, while BrdU incorporation was similar in control and YM155-treated MSCs, suggesting that Survivin is primarily involved in MSC survival. To explore whether Survivin is also involved in growth factor-mediated MSC survival and expansion, mouse bone marrow derived MSCs were cultured in the presence of platelet derived growth factor (PDGF) or basic fibroblast growth factor (b-FGF) with or without the Survivin inhibitor YM155. PDGF enhanced the Survivin expression by 52.8±2.2% and b-FGF enhanced Survivin expression by 43.8±4.5% and increased the CFU-F counts by 5.6 fold and 4.2 fold, respectively. In contrast, YM155 treated MSCs did not show any enhancement in Survivin expression, and CFU-F were substantially lower than the corresponding controls (PDGF or b-FGF treated cultures). To determine whether Survivin affects the Survival of stressed MSCs, we exposed mouse bone marrow MSCs to 4 Gy irradiation dose and followed by culture for 3 days with or without the Survivin inhibitor YM155. Irradiation alone reduced the survival of MSCs by 53.5%, however the viability of irradiated MSCs treated with YM155 was reduced by 82.8%. The hallmark of MSC function is the capacity to differentiate into several mesodermal lineages. We found that the exposure of MSC cultures to YM155 during the lineage differentiation process inhibits MSC osteogenic and adipogenic differentiation while sparing chondrogenic cell differentiation. In conclusion, our study demonstrates that Survivin controls basal and growth factor dependent survival and expansion of mouse and human MSCs, and protects them from irradiation induced cell death. Furthermore, our data suggest the regulating Survivin expression in MSCs would be beneficial to enhance MSC recovery for clinical utility. Disclosures No relevant conflicts of interest to declare.


2014 ◽  
Vol 11 (96) ◽  
pp. 20140233 ◽  
Author(s):  
J. Zhao ◽  
S. Zeiai ◽  
Å. Ekblad ◽  
A. Nordenskjöld ◽  
J. Hilborn ◽  
...  

Urological reconstructive surgery is sometimes hampered by a lack of tissue. In some cases, autologous urothelial cells (UCs) are not available for cell expansion and ordinary tissue engineering. In these cases, we wanted to explore whether autologous mesenchymal stem cells (MSCs) from bone marrow could be used to create urological transplants. MSCs from human bone marrow were cultured in vitro with medium conditioned by normal human UCs or by indirect co-culturing in culture well inserts. Changes in gene expression, protein expression and cell morphology were studied after two weeks using western blot, RT-PCR and immune staining. Cells cultured in standard epithelial growth medium served as controls. Bone marrow MSCs changed their phenotype with respect to growth characteristics and cell morphology, as well as gene and protein expression, to a UC lineage in both culture methods, but not in controls. Urothelial differentiation was also accomplished in human bone marrow MSCs seeded on a three-dimensional poly(ε-caprolactone) (PCL)–collagen construct. Human MSCs could easily be harvested by bone marrow aspiration and expanded and differentiated into urothelium. Differentiation could take place on a three-dimensional hybrid PCL-reinforced collagen-based scaffold for creation of a tissue-engineered autologous transplant for urological reconstructive surgery.


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