Mesenchymal stem cells (MSCs) are multipotent stem cells which can support hematopoiesis, have immunomodulatory property, may differentiate into osteocytes, chondrocytes and adipocytes, and specifically migrate to damage sites and tumor site, but the mechanism involved in the regulation of migration of MSCs still remains unelucidated. Understanding the fundamental mechanisms underlying MSCs migration holds the promise of developing novel clinical strategies which can deliver antitumor proteins to suppress tumor growth. In this review, the MSC migration in vitro mediated by growth factors, chemokines, adhesion molecules and toll-like receptors are summarized.
Cell Movement ; physiology ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism

Bone marrow mesenchymal stem cells (MSCs) are somatic stem cells that can differentiate into progenies of multiple lineages. They play an important role in hematopoiesis and stem cell therapy due to their multi-lineage potentials and immunomodulatory properties. Oxidative stress is a disturbed redox state caused by accumulation of reactive oxygen species. It can induce the senescence and apoptosis of MSCs via phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and p53 pathways, and inhibit the proliferation and differentiation of MSCs through apurinic/apyrimidinic endonuclease/redox factor 1 (APE/REF-1) and extracellular signal-regulated kinase (ERK) pathways. Furthermore, using anti-stress medication and hypoxic preconditioning, the functions of MSCs can be further enhanced. Accordingly, further studies on the effect of oxidative stress on MSCs and its signaling pathways may be meaningful for the treatment of hematologic diseases and for improving stem cell therapy.
Bone Marrow Cells ; cytology ; metabolism ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Oxidative Stress ; Signal Transduction

OBJECTIVETo investigate the role of mesenchymal stem cells (BMSCs) in multiple myeloma (MM) bone marrow (BM) microenrivonment and their effect on myeloma cells survival and bortezomib induced apoptosis.

METHODSBMSCs were derived from BM of untreated myeloma patients (MM-BMSCs) and healthy donors (HD-BMSCs), respectively. The phenotype, proliferation time and cytokine secretion of MM-BMSCs were detected and compared with HD-BMSCs. Then BMSCs were co-cultured with myeloma cell line NCI-H929 and bortezomib in vitro. The NCI-H929 cells proliferation and bortezomib induced cell apoptosis were investigated.

RESULTSMM-BMSCs and HD-BMSCs were isolated successfully. The phenotype of MM-BMSCs was similar to that of HD-BMSCs. Expressions of CD73, CD105, CD44 and CD29 were positive, but those of CD31, CD34, CD45 and HLA-DR (< 1%) negative. The proliferation time of MM-BMSCs was longer than that of HD-BMSCs (82 h vs 62 h, P < 0.05). Moreover, over-expressions of IL-6 and VEGF in MM-BMSCs culture supernatant were detected as compared with that in HD-BMSCs [(188.8 ± 9.4) pg/ml vs (115.0 ± 15.1) pg/ml and (1497.2 ± 39.7) pg/ml vs (1329.0 ± 21.1) pg/ml, respectively]. MM- BMSCs supported survival of the myeloma cells NCI-H929 and protected them from bortezomib induced cell apoptosis.

CONCLUSIONSMM-BMSCs is benefit for myeloma cells proliferation and against cell apoptosis induced by bortezomib. Over-expression of IL-6 and VEGF maybe play a critical role in these effects.

Apoptosis ; drug effects ; Bone Marrow Cells ; cytology ; Bortezomib ; Humans ; Mesenchymal Stromal Cells ; metabolism ; Multiple Myeloma ; metabolism

Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells with highly self-renewal and multilineage differentiation potential. Because MSC can be easily obtained and expanded in large amount in vitro, they have become a hot field of stem cell research in recent years. MSC as a seed carrier of cells and gene therapy have been widely used in cardiovascular, nervous, respiratory diseases, wound healing and other aspects in clinic. But some biological characteristics and the molecular control mechanisms of MSC are not very clear and need further explorations. The MSC isolated and cultured in vitro are a type of multipotent differentiation cells, which differentiation potential in vivo has still uncertained, the effectiveness and safety such as gene mutations and canceration in vivo remains to be explored. Deepgoing studys on homing characteristics, mechanisms and influence factors of MSC also contribute to the clinical application, and the studys on the MSC differentiation fate in microenvironment in vivo would be better for clinical application. So how stably and efficiently label MSC in vitro is the key problem to monitoring the survival, migration, distribution, proliferation and differentiation of MSC in vivo. This review summarizes the current progress of study on the new labeling methods in vitro of MSC, discussing the advantages and disadvantages of different in vitro labeling methods and application of appropriate conditions.
Biomarkers ; metabolism ; Cell Differentiation ; Cells, Cultured ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; physiology

Mesenchymal stem cell-derived microvesicle (MSC-MV) is a membrane secretory system which includes microparticle and exosome, and MSC-MV is released by MSC in resting or activated state. MSC-MV selectively package the biological active substances such as lipids, proteins, mRNA and miRNA but not loads them randomly. It has definitive effect of reducing tissue injury, promoting morphological and functional recovery of the injured tissue, and this effect is probably mediated by miRNA. What is more, the MSC-MV may also possess the biological function of immunological regulation, modulation of cell growth and differentiation. The generation, constitution, and function of MSC-MV are reviewed in this article.
Animals ; Cell-Derived Microparticles ; metabolism ; Humans ; Mesenchymal Stromal Cells ; metabolism ; MicroRNAs ; metabolism

The release of microvesicles(MV) is one of the critical mechanisms underlying the angiogenesis-promoting activity of mesenchymal stem cells(MSC). This study was aimed to explore the appropriate condition under which MSC releases MV. Bone marrow samples from 5 healthy adults were collected, and MSC were isolated, culture-expanded and identified. MSC at passage 5 were suspended in medium without or medium with 10% fetal(FCS) calf serum and seeded into culture dishes. The culture was separately maintained in hypoxia (1% oxygen) or normoxia (around 20% oxygen), and 20 dishes of cells (2×10(6)/dish) were used for each group. The supernatants were collected for MV harvesting. The cell number was counted with trypan blue exclusion test and the protein contents in the MV were determined. MV were identified by observation under an electron microscope. The surface markers on MV were analyzed by flow cytometry. MTT test was performed to observe the pro-proliferative activity of MV that were added into the culture of human umbilical cord vein endothelial cells at a concentration of 10 µg/ml. The results showed that the majority of MV released by MSC were with diameters of less than 100 nm, and MV took the featured membrane-like structure with a hypodense center. They expressed CD29, CD44, CD73 and CD105, while they were negative for CD31 and CD45. The increase multiples of the adherent trypan blue-resistant cells cultured in normoxia with serum, in normoxia without serum, in hypoxia with serum and hypoxia in the absence of serum were 4.05 ± 0.73, 1.77 ± 0.48, 5.80 ± 0.65 and 3.69 ± 0.85 respectively, and the estimated protein contents per 10(8) cells were 463.48 ± 138.74 µg, 1604.07 ± 445.28 µg, 2389.64 ± 476.75 µg and 3141.18 ± 353.01 µg. MTT test showed that MV collected from MSC in hypoxia seemed to promote the growth of endothelial cells more efficiently than those from cells in normoxia. It is concluded that hypoxia can enhance the release of microvesicles from MSC, and cultivation of MSC in hypoxia and medium without serum may provide an appropriate condition for MV harvesting.
Bone Marrow Cells ; cytology ; metabolism ; Caveolae ; metabolism ; Cell-Derived Microparticles ; metabolism ; Cells, Cultured ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism

The aim of this study was to explore the characteristics of Toll-like receptor expression in mesenchymal stem cells derived from bone marrow of healthy donor (BM-MSCs). BM-MSCs were isolated from bone marrow of healthy donor by Ficoll method. Expressions of CD34, CD45, HLA-DR, CD44 and CD71 in BM-MSCs were detected by flow cytometry. CD71 in BM-MSCs was assayed by immunocytochemistry. The adipocyte and osteoblast induction of BM-MSCs were detected by alizarin red stain and oil red stain respectively. TLR 1 - 10 mRNA levels in BM-MSCs were evaluated by semiquantitative RT-PCR. The results showed that expressions of CD34, CD45 and HLA-DR in BM-MSC were negative while the expressions of CD44 and CD71 were positive. CD71 in BM-MSCs was positive. After induced by osteoblast and adipocyte inductor, BM-MSCs were positive for alizarin red staining and oil red staining respectively. All of TLR 1 - 10 mRNA were found in BM-MSCs with high expression levels of TLR2, TLR3, TLR4, TLR7, TLR8, TLR9 and low expression levels of TLR1, TLR5, TLR6, TLR10. In conclusion, different levels of TLR 1 - 10 mRNA were expressed in BM-MSCs of healthy donor.
Bone Marrow Cells ; metabolism ; Cell Differentiation ; Cells, Cultured ; Humans ; Mesenchymal Stromal Cells ; metabolism ; RNA, Messenger ; genetics ; Toll-Like Receptors ; metabolism

Mesenchymal stem cell (MSC) is an adult stem cell which has the multipotential differentiation ability. In vitro experiments demonstrated that MSC is able to differentiate into various lineage cells including bone, cartilage, fat, and muscle cells. In addition, MSC has also been shown to differentiate into neural precursors, cardiomyocytes, liver cells, and possible other cell types. The Notch pathway is a highly conserved signaling mechanism involved in many processes determining cell fate during the animal development, and plays an important role in the regulation of cell differentiation, proliferation and apoptosis. Notch ligands and receptors are both transmembrane proteins, and suggest that Notch-mediated cellular interaction is an important way in cell to cell communication. Studies of Notch function provide evidence that Notch signaling affects various differentiation capabilities of MSC. In this review, the roles of Notch signaling in differentiation of MSC are summarized.
Animals ; Cell Differentiation ; Drosophila ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Receptors, Notch ; metabolism ; Signal Transduction

Mesenchymal stem cells (MSC) are capable of immunosuppression and differentiating into multiple cell lineages. MSC, which are accessed easily and less side-effects, have been a source of seed cells in tissue-engineering and cell-therapy. However, the application of MSC are limited by their differentiation of instability and easy aging. MicroRNA-155 (miR-155) is one of microRNA, which has powerful regulatory potential in a wide variety of immune cells through degrading specific mRNA after transcription and inhibiting translation of the target genes. Following the research of miR-155 deeply, it has an indispensable role in the proliferation, differentiation and immunoregulation of MSC. This review discusses the current understandings for the role of miR-155 in MSC.
Cell Differentiation ; Cell Lineage ; Humans ; Mesenchymal Stromal Cells ; metabolism ; MicroRNAs ; metabolism

OBJECTIVETo investigate the IL-32 mRNA expression of bone marrow stromal cells and its correlation with apoptosis of bone marrow mononuclear cells in patients with myelodysplastic syndrome (MDS).

METHODSBone marrow samples from 26 MDS patients and 10 iron deficiency anemia (IDA, as control) patients were collected, RT-PCR was used to detect the IL-32 mRNA expression of bone marrow stromal cells, and the apoptosis of bone marrow mononuclear cells was detected by flow cytometry with Annexin V-FITC/PI dowble staining. The born marrow lymphocytes and NK cells were detected by means of direct immunofluorescence labeling whole blood hemolysis and flow cytometry.

RESULTSIL-32 mRNA expression of bone marrow stromal cells in the MDS patients was significantly higher than that of control group, the IL-32 mRNA expression of bone marrow stromal cells in patients with RA, RAS and RCMD was significantly higher than that in patients with RAEB. There was no obvious difference between RAEB and the control groups. The apoptosis of bone marrow mononuclear cells in MDS group was significantly higher than that in the control group, the apoptosis of bone marrow mononuclear cells in patients with RA, RAS and RCMD was significantly higher than that in RAEB. There was no significant difference between RAEB group and control group. The IL-32 mRNA expression in bone marrow stromal cells significantly correlated with the apoptosis of bone marrow mononuclear cells in MDS patients. The NK cell number in born marrow of MDS patients and the control group had no significant difference.

CONCLUSIONThe expression of IL-32 mRNA in bone marrow stromal cells significantly relates with the apoptosis of MDS cells, and the secretion of IL-32 by bone marrow stromal cells may be one of the reasons for the apoptosis of MDS bone marrow cells. It is speculated that the abnormal MDS bone marrow microenvironment is involved in the apoptosis of bone marrow cells.

Apoptosis ; Bone Marrow Cells ; metabolism ; Flow Cytometry ; Humans ; Interleukins ; metabolism ; Mesenchymal Stromal Cells ; metabolism ; Myelodysplastic Syndromes ; pathology ; RNA, Messenger ; metabolism