Effect Of BM-MSCs Research Articles

Study on Application of Bone Marrow Mesenchymal Stem Cells Transplantation in Restorative Treatment of Spinal Cord Injury in Mice

The spinal cord injury (SCI) refers to different degrees of injuries in the structure or function of spinal cord caused by different factors. The prevalence rate of SCI in the population under 40 years reaches 80%. SCI causes certain injury to both physiology and psychology of patients. An important factor leading to SCI is the rupture of nerve fibers. Bone marrow mesenchymal stem cells (BMMSCs) have the functions of inducing and supporting hematopoietic stem cells in bone marrow. In this study, SCI mouse model was established to assess the effect of BM-MSCs on SCI. A total of 30 SCI mouse model were established and assigned into transplantation group (15 mice) and control group (15 mice) according to random number table method. The mice in transplantation group were treated with BM-MSCs transplantation at SCI site, while mice in control group were treated with normal saline at SCI site. The bone marrow pathological changes were measured by HE staining and neural cells were assessed by Pischingert's methylene blue staining along with measuring SRY level by immunohistochemistry. The motor abilities of mice in transplantation group at the 2nd, 4th, 6th and 8th weeks were significantly higher than mice in control group (P < 0 05). A few vacuoles appeared in mice in transplantation group. The number of cells in mouse spinal cord tissues in transplantation group was increased significantly over time, but a large number of vacuoles appeared in mouse spinal cord tissues in control group with necrosis of a vast amount of nerve fibers (P < 0 05). The number and volume of Nissl bodies in mice in transplantation group was increased significantly at 2 weeks after treatment and degeneration status of nerve cells in transplantation group was significantly better than control group (P < 0 05). The SRY genes were expressed in transplantation group for a long term but not in control group (P < 0 05). The number of adherent cells increased significantly in transplantation group at 48 hours after treatment. BMMSCs transplantation can effectively promotes the recovery of SCI mice, indicating that it is worthy of clinical promotion and application.

Potential Therapeutic Effect of Allogenic Mesenchymal Stem Cells on Chronic Cerebral Murine Toxoplasmosis

Background and Aim: Toxoplasma infection is mainly latent and cause severe disease only if reactivation occurs especially for brain cysts. This study aimed to evaluate the therapeutic effect of BM-MSCs on murine chronic toxoplasmosis experimental model. Methods: Female Swiss albino mice (n=100) were divided into 5 groups (20 mice each). Group I (infected, injected with BM-MSCs); Group II (infected, treated with BM-MSCs and Spiramycin-Metronidazole); Group III (infected, treated with Spiramycin-Metronidazole); Group IV (infection control) and Group V (non infected, injected with BM-MSCs). Results: In Regarding the mean Toxoplasma brain cyst count, after 7 and 14 days, group I was significantly lower than group II, higher than group III and non-statistically different from group IV. Group II was significantly higher than in groups III and IV. Group III showed a significant decrease in brain cyst count versus group IV. As regards the histopathological examination of brain sections, after 7 and 14 days, group I showed the least histopathological inflammatory changes which was significantly lower than that of group IV. Group II revealed the most profound histopathological inflammatory changes. Group III showed mild to moderate inflammatory changes with a non-significant difference from group IV. As regards the survival rate, the group I showed the highest, group II showed the lowest mean survival time, which was statistically significant versus group IV. Group III showed a non-significant difference versus group IV. Conclusion: MSCs have an anti-inflammatory effect and prolong the survival of T. gondii infected mice; however, they have a non

Transplantation of bone-marrow-derived mesenchymal stem cells into a murine model of immune thrombocytopenia.

: Several reports have demonstrated T regulatory cells may play an important role in the pathophysiology of immune thrombocytopenia (ITP). As the immunomodulator, bone-marrow-derived mesenchymal stem cells (MSCs) (BM-MSCs) regulate T regulatory cells and show therapeutic effects on autoimmune diseases. However, it is not clear how BM-MSCs affect ITP. In this study, we explored the specific effects of BM-MSCs on ITP in mice. Using a murine model of ITP, mice were randomly divided into three groups: normal control group, ITP control group and ITP and BM-MSCs group. Platelet (PLT) levels were monitored by an automatic blood cell counter, and T regulatory cells were analyzed by flow cytometry. Compared with the untreated ITP mice, the PLT level of the ITP mice was significantly increased after BM-MSCs treatment. In the BM-MSCs group, T regulatory cells were significantly decreased. These findings demonstrate that bone-marrow-derived MSCs are effective in improving PLT levels and reducing the T regulatory cells mediating proinflammatory response in ITP mice.

Human graft-derived mesenchymal stromal cells potently suppress alloreactive T-cell responses.

After organ transplantation, recipient T cells contribute to graft rejection. Mesenchymal stromal cells from the bone marrow (BM-MSCs) are known to suppress allogeneic T-cell responses, suggesting a possible clinical application of MSCs in organ transplantation. Human liver grafts harbor resident populations of MSCs (L-MSCs). We aimed to determine the immunosuppressive effects of these graft-derived MSCs on allogeneic T-cell responses and to compare these with the effects of BM-MSCs. BM-MSCs were harvested from aspirates and L-MSCs from liver graft perfusates. We cultured them for 21 days and compared their suppressive effects with the effects of BM-MSCs on allogeneic T-cell responses. Proliferation, cytotoxic degranulation, and interferon-gamma production of alloreactive T cells were more potently suppressed by L-MSCs than BM-MSCs. Suppression was mediated by both cell-cell contact and secreted factors. In addition, L-MSCs showed ex vivo a higher expression of PD-L1 than BM-MSCs, which was associated with inhibition of T-cell proliferation and cytotoxic degranulation in vitro. Blocking PD-L1 partly abrogated the inhibition of cytotoxic degranulation by L-MSCs. In addition, blocking indoleamine 2,3-dioxygenase partly abrogated the inhibitive effects of L-MSCs, but not BM-MSCs, on T-cell proliferation. In conclusion, liver graft-derived MSC suppression of allogeneic T-cell responses is stronger than BM-MSCs, which may be related to in situ priming and mobilization from the graft. These graft-derived MSCs may therefore be relevant in transplantation by promoting allohyporesponsiveness.

Culture medium of bone marrow-derived human mesenchymal stem cells effects lymphatic endothelial cells and tumor lymph vessel formation.

Human bone marrow mesenchymal stem cells (hBM-MSCs) favor tumor growth and metastasis in vivo and in vitro. Neovascularization is involved in several pathological conditions, including tumor growth and metastasis. Previous studies have demonstrated that human bone marrow MSC-derived conditioned medium (hBM-MSC-CM) can promote tumor growth by inducing the expression of vascular epidermal growth factor (VEGF) in tumor cells. However, the effect of BM-MSCs on tumor lymph vessel formation has yet to be elucidated. In the present study, the effect of BM-MSCs on processes involved in lymph vessel formation, including tube formation, migration and proliferation, was investigated in human-derived lymphatic endothelial cells (HDLECs). It was identified that hBM-MSC-CM promoted the tube formation and migration of HDLECs. In addition, tumor cells were revealed to participate in lymph vessel formation. In the present study, the SGC-7901, HGC-27 and GFP-MCF-7 cell lines were treated with hBM-MSC-CM. The results demonstrated that the expression of the lymph-associated markers, prospero homeobox protein 1 and VEGF receptor-3, were increased in the SGC-7901 and HGC-27 cell lines, but not in the GFP-MCF-7 cells. The tube formation assay demonstrated that the HGC-27 cells treated with hBM-MSC-CM for 20 days underwent tube formation. These findings indicate that hBM-MSC-CM can promote tube formation in HDLECs and HGC-27 cells, which may be associated with lymph vessel formation during tumor growth and metastasis.

Abstract C38: Immunosuppression by indoleamine 2,3-dioxygenase in mesenchymal stem cells derived from adult human tissues

Abstract Mesenchymal stem cells (MSCs), which evoke only minimal immune reactivity, may have anti-inflammatory and immunomodulatory effects. In this study, we conducted a comparative analysis of the immunomodulatory properties of MSCs derived from adult human tissues including bone marrow (BM), adipose tissues (AT), umbilical cord blood (CB), and cord Wharton's jelly (WJ). Using a multiple cytokine detection assay, we showed that there were no significant differences in levels of secreted factors from non-stimulated MSCs. We compared the immunosuppressive effect of BM-MSCs, AT-MSCs, CB-MSCs, and WJ-MSCs on phytohemagglutinin (PHA)-induced T-cell proliferation. AT-MSCs, CB-MSCs, and WJ-MSCs effectively suppressed PHA-induced T-cell proliferation as effectively as did BM-MSCs. Levels of interferon (IFN)-γ secreted from activated T-cells increased over time, but these levels were significantly reduced when cocultured with each type of MSCs. In addition, the expression of hepatocyte growth factor, interleukin-10, transforming growth factor-β1, cyclooxygenase (COX)-1, and COX-2 were unchanged in MSCs treated with IFN-γ, while that of indoleamine 2,3-dioxygenase (IDO) increased. Use of an antagonist, 1-methyl-L-tryptophan, restored T-cell proliferation and confirmed an IDO contribution to IFN-γ-induced immunosuppression by MSCs. Addition of tryptophan catabolite, such as kynurenine, 3-hydroxykynurenine, or quinolinic acid, significantly decreased PHA-induced T-cell proliferation. These data indicate that IFN-γ produced by activated T-cells were correlated with induction of IDO expression by MSCs, which, in turn, suppressed T-cell proliferation through tryptophan depletion and the local accumulation of tryptophan catabolites. Our findings suggest that MSCs derived from AT, CB, or WJ could be substituted for BM-MSCs for treatment of allogeneic conflicts. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C38.