Abstract 5539: Mesenchymal stem cell altruism mediates a novel HMGB1/NKG2D immune response in oral cancer

Author(s):  
Seema Bhuyan ◽  
Bidisha Pal ◽  
Hong Li ◽  
Rashmi Bhuyan ◽  
Lekhika Pathak ◽  
...  
2018 ◽  
Vol 67 (10) ◽  
pp. 1589-1602 ◽  
Author(s):  
Álvaro Morales-Molina ◽  
Stefano Gambera ◽  
Teresa Cejalvo ◽  
Rafael Moreno ◽  
Miguel Ángel Rodríguez-Milla ◽  
...  

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 577
Author(s):  
Marina Gomzikova ◽  
Sevindzh Kletukhina ◽  
Sirina Kurbangaleeva ◽  
Olga Neustroeva ◽  
Olga Vasileva ◽  
...  

Immune-mediated diseases are characterized by abnormal activity of the immune system. The cytochalasin B-induced membrane vesicles (CIMVs) are innovative therapeutic instruments. However, the immunomodulating activity of human mesenchymal stem cell (MSC)-derived CIMVs (CIMVs-MSCs) remains unknown. Therefore, we sought to investigate the immunological properties of CIMVs-MSCs and evaluate their effect on human peripheral blood mononuclear cells (PBMCs). We found that CIMVs-MSCs are primarily uptaken by monocytes and B-cells. Additionally, we demonstrated that CIMVs-MSCs inhibit phytohemagglutinin (PHA)-induced proliferation of PBMCs, with more pronounced effect on T-lymphocytes expansion as compared to that of B-cells. In addition, activation of T-helpers (CD4+CD25+), B-cells (CD19+CD25+), and T-cytotoxic lymphocytes (CD8+CD25+) was also significantly suppressed by CIMVs-MSCs. Additionally, CIMVs-MSCs decreased secretion of epidermal growth factor (EGF) and pro-inflammatory Fractalkine in a population of PBMCs, while the releases of FGF-2, G-CSF, anti-inflammatory GM-CSF, MCP-3, anti-inflammatory MDC, anti-inflammatory IL-12p70, pro-inflammatory IL-1b, and MCP-1 were increased. We analyzed the effect of CIMVs-MSCs on an isolated population of CD4+ and CD8+ T-lymphocytes and demonstrated their different immune response and cytokine secretion. Finally, we observed that no xenogeneic nor allogeneic transplantation of CIMVs induced an immune response in mice. Our data suggest that CIMVs-MSCs have immunosuppressive properties, are potential agents for immunomodulating treatment, and are worthy of further investigation.


Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5683
Author(s):  
A. Thirumal Raj ◽  
Supriya Kheur ◽  
Zohaib Khurshid ◽  
Mohammed E. Sayed ◽  
Maryam H. Mugri ◽  
...  

Background: Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis. The impact and effects of these secretory factors on cancer cells must be understood in order to ensure their safe application in cancer patients. Objective: We aimed to quantify the growth factors and cytokines in DPMSC-S and assess their effect on oral cancer cell proliferation. Materials and methods: DPMSCs were isolated from patients with healthy teeth (n = 5) that were indicated for extraction for orthodontic reasons. The cells were characterized using flow cytometry and conditioned medium (DPMSC-CM) was prepared. DPMSC-CM was subjected to a bead-based array to quantify the growth factors and cytokines that may affect oral carcinogenesis. The effect of DPMSC-CM (20%, 50%, 100%) on the proliferation of oral cancer cells (AW123516) was evaluated using a Ki-67-based assay at 48 h. AW13516 cultured in the standard growth medium acted as the control. Results: VEGF, HCF, Ang-2, TGF-α, EPO, SCF, FGF, and PDGF-BB were the growth factors with the highest levels in the DPMSC-CM. The highest measured pro-inflammatory cytokine was TNF-α, followed by CXCL8. The most prevalent anti-inflammatory cytokine in the DPMSC-CM was IL-10, followed by TGF-β1 and IL-4. Concentrations of 50% and 100% DPMSC-CM inhibited Ki-67 expression in AW13516, although the effect was non-significant. Moreover, 20% DPMSC-CM significantly increased Ki-67 expression compared to the control. Conclusions: The increased Ki-67 expression of oral cancer cells in response to 20% DPMSC-CM indicates the potential for cancer progression. Further research is needed to identify their effects on other carcinogenic properties, including apoptosis, stemness, migration, invasion, adhesion, and therapeutic resistance.


Author(s):  
Vladislav Volarevic ◽  
Jelena Jakovljevic ◽  
C. Randall Harrell ◽  
Crissy Fellabaum ◽  
Nebojsa Arsenijevic

2020 ◽  
Vol 39 (4) ◽  
pp. S361
Author(s):  
S.J. Bozso ◽  
J.J. Kang ◽  
B. Adam ◽  
M.C. Moon ◽  
D.H. Freed ◽  
...  

Author(s):  
Sabin J Bozso ◽  
Jimmy J H Kang ◽  
Ryaan EL-Andari ◽  
Nicholas Fialka ◽  
Lin Fu Zhu ◽  
...  

Abstract OBJECTIVES Our aim was to address the role of autologous mesenchymal stem cell recellularization of xenogenic valves on the activation of the xenoreactive immune response in an in vivo rat model. METHODS Explanted aortic valve constructs from female Hartley guinea pigs were procured and decellularized, followed by recellularization with autologous Sprague-Dawley rat mesenchymal stem cells. Aortic valve xenografts were then implanted into the infrarenal aorta of recipient rats. Grafts were implanted as either autologous grafts, non-decellularized (NGP), decellularized and recellularized xenografts (RGP). Rats were euthanized after 7 and 21 days and exsanguinated and the grafts were explanted. RESULTS The NGP grafts demonstrated significant burden of granulocytes (14.3 cells/HPF) and CD3+ T cells (3.9 cells/HPF) compared to the autologous grafts (2.1 granulocytes/HPF and 0.72 CD3+ T cells/HPF) after 7 days. A lower absolute number of infiltrating granulocytes (NGP vs autologous, 6.4 vs 2.4 cells/HPF) and CD3+ T cells (NGP vs autologous, 2.8 vs 0.8 cells/HPF) was seen after 21 days. Equivalent granulocyte cell infiltration in the RGP grafts (2.4 cells/HPF) compared to the autologous grafts (2.1 cells/HPF) after 7 and 21 days (2.8 vs 2.4 cells/HPF) was observed. Equivalent CD3+ T-cell infiltration in the RGP grafts (0.63 cells/HPF) compared to the autologous grafts (0.72 cells/HPF) after 7 and 21 days (0.7 vs 0.8 cells/HPF) was observed. Immunoglobulin production was significantly greater in the NGP grafts compared to the autologous grafts at 7 (123.3 vs 52.7 mg/mL) and 21 days (93.3 vs 71.6 mg/mL), with a similar decreasing trend in absolute production. Equivalent immunoglobulin production was observed in the RGP grafts compared to the autologous grafts at 7 (40.8 vs 52.7 mg/mL) and 21 days (29.5 vs 71.6 mg/mL). CONCLUSIONS Autologous mesenchymal stem cell recellularization of xenogenic valves reduces the xenoreactive immune response in an in vivo rat model and may be an effective approach to decrease the progression of xenograft valve dysfunction.


Sign in / Sign up

Export Citation Format

Share Document