scholarly journals Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 446 ◽  
Author(s):  
Jui-Hua Lu ◽  
Bou-Yue Peng ◽  
Chun-Chao Chang ◽  
Navneet Dubey ◽  
Wen-Cheng Lo ◽  
...  

Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, such as improperly immortalized mesenchymal stem cells (MSCs) along with transfected oncogenic antigens in them. To overcome the limitations of this platform for future clinical application, we freshly prepared primary adipose-derived stem cells (ADSCs) and modified the E7’ antigen (E7’) as a non-oncogenic protein. Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, ADSC labeled with enhanced green fluorescent protein (eGFP) and combined with modified E7’ (ADSC-E7’-eGFP) cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. Specifically, this combined therapy inhibited tumor through inducing cell apoptosis. The significantly reduced endothelial cell markers, CD31 and vascular endothelial growth factor (VEGF), indicated strongly inhibited tumor angiogenesis. The activated immune system was demonstrated through the response of CD4+ T and natural killer (NK) cells, and a notable antitumor activity might be contributed by CD8+ T cells. Conclusively, these evidences imply that this promising immunotherapeutic platform might be a potential candidate for the future clinical application against cancer.

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Barbara Hersant ◽  
Mounia Sid-Ahmed ◽  
Laura Braud ◽  
Maud Jourdan ◽  
Yasmine Baba-Amer ◽  
...  

Chronic and acute nonhealing wounds represent a major public health problem, and replacement of cutaneous lesions by the newly regenerated skin is challenging. Mesenchymal stem cells (MSC) and platelet-rich plasma (PRP) were separately tested in the attempt to regenerate the lost skin. However, these treatments often remained inefficient to achieve complete wound healing. Additional studies suggested that PRP could be used in combination with MSC to improve the cell therapy efficacy for tissue repair. However, systematic studies related to the effects of PRP on MSC properties and their ability to rebuild skin barrier are lacking. We evaluated in a mouse exhibiting 4 full-thickness wounds, the skin repair ability of a treatment combining human adipose-derived MSC and human PRP by comparison to treatment with saline solution, PRP alone, or MSC alone. Wound healing in these animals was measured at day 3, day 7, and day 10. In addition, we examined in vitro and in vivo whether PRP alters in MSC their proangiogenic properties, their survival, and their proliferation. We showed that PRP improved the efficacy of engrafted MSC to replace lost skin in mice by accelerating the wound healing processes and ameliorating the elasticity of the newly regenerated skin. In addition, we found that PRP treatment stimulated in vitro, in a dose-dependent manner, the proangiogenic potential of MSC through enhanced secretion of soluble factors like VEGF and SDF-1. Moreover, PRP treatment ameliorated the survival and activated the proliferation of in vitro cultured MSC and that these effects were accompanied by an alteration of the MSC energetic metabolism including oxygen consumption rate and mitochondrial ATP production. Similar observations were found in vivo following combined administration of PRP and MSC into mouse wounds. In conclusion, our study strengthens that the use of PRP in combination with MSC might be a safe alternative to aid wound healing.


2017 ◽  
Vol 03 ◽  
pp. 66
Author(s):  
I Gusti Ayu Putri Purwanthi ◽  
Ketut Kris Adi Marta ◽  
I Gusti Kadek Satrio Adiwardhana ◽  
◽  
◽  
...  

Osteoarthritis (OA) is the most common form of arthritis that affects cartilage joints and leads to disability. OA becomes the major public health problem, as it is the most leading cause of disability and morbidity worldwide. Treatment choices for OA can be classified into several categories such as non-pharmacologic, pharmacologic, surgical therapy, and cell-based therapy. There is no curative treatment for OA, while conventional treatments that are commonly used focus on alleviating the pain as the main symptom of the disease. Mesenchymal stem cells (MSCs) that can be found in several tissues of human body offer a new strategy for OA treatment owing to their ability to differentiate into chondrocytes. This article provides an overview about the basic concept of osteoarthritis as well as an insight about the MSCs therapy, including their basic characteristics, source, and transplantation strategies in the OA area.


2013 ◽  
Vol 2 (2) ◽  
pp. 107-117 ◽  
Author(s):  
Eugenio Broccaioli ◽  
Stefania Niada ◽  
Giulio Rasperini ◽  
Lorena Maria Ferreira ◽  
Elena Arrigoni ◽  
...  

2013 ◽  
Vol 14 (3) ◽  
pp. 367 ◽  
Author(s):  
Jun-Gu Kang ◽  
Sang-Bum Park ◽  
Min-Soo Seo ◽  
Hyung-Sik Kim ◽  
Joon-Seok Chae ◽  
...  

2021 ◽  
Vol 22 (22) ◽  
pp. 12194
Author(s):  
Jin Hyoung Cho ◽  
Won Seok Ju ◽  
Sang Young Seo ◽  
Bo Hyun Kim ◽  
Ji-Su Kim ◽  
...  

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.


2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Jin-Woo Park ◽  
Yusuke Tsutsumi ◽  
Eui-Kyun Park

The manganese (Mn) ion has recently been probed as a potential candidate element for the surface chemistry modification of titanium (Ti) implants in order to develop a more osteogenic surface with the expectation of taking advantage of its strong binding affinity to the integrins on bone-forming cells. However, the exact mechanism of how Mn enhances osteogenesis when introduced into the surface of Ti implants is not clearly understood. This study investigated the corrosion resistance and potential osteogenic capacity of a Mn-incorporated Ti surface as determined by electrochemical measurement and examining the behaviors of human mesenchymal stem cells (MSCs) in a clinically available sandblasted/acid-etched (SLA) oral implant surface intended for future biomedical applications. The surface that resulted from wet chemical treatment exhibited the formation of a Mn-containing nanostructured TiO2 anatase thin film in the SLA implant and improved corrosion resistance. The Mn-incorporated SLA surface displayed sustained Mn ion release and enhanced osteogenesis-related MSC function, which enhanced early cellular events such as spreading, focal adhesion, and mRNA expression of critical adhesion-related genes and promoted full human MSC differentiation into mature osteoblasts. Our findings indicate that surface Mn modification by wet chemical treatment is an effective approach to produce a Ti implant surface with increased osteogenic capacity through the promotion of the osteogenic differentiation of MSCs. The improved corrosion resistance of the resultant surface is yet another important benefit of being able to provide favorable osseointegration interface stability with an increased barrier effect.


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