Halimeh Hassanzadeh; Ahmad Reza Bahrami; Hamidreza Bidkhori; Maryam M. Matin
Abstract
Transplantation of mesenchymal stem cells (MSCs) is a promising strategy in regenerative medicine. These cells can differentiate into chondrocytes, fibroblasts, or osteoblasts, essential components in bone healing. Dysregulated inflammation, resulting from a decreased or augmented immune response, can ...
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Transplantation of mesenchymal stem cells (MSCs) is a promising strategy in regenerative medicine. These cells can differentiate into chondrocytes, fibroblasts, or osteoblasts, essential components in bone healing. Dysregulated inflammation, resulting from a decreased or augmented immune response, can suppress bone healing. To overcome this problem, different strategies have been applied to improve the anti-inflammatory and immunomodulatory potencies of MSCs. Several studies have explored the potential of using small molecules to enhance the process of bone formation and regeneration. In addition to the proven safety and efficacy of lithium in managing bipolar disorder over many years, it has been reported in several studies that it could potentially contribute to an increase in bone mass. Some have focused on the role of lithium chloride (LiCl) in activating the WNT/β-Catenin pathway, which is involved in the differentiation of MSCs into osteoblasts. In this study, we evaluated the ability of adipose-derived mesenchymal stem cells (Ad-MSCs) treated with LiCl to differentiate into bone cells. To assess osteogenesis, mineralization was evaluated in cells cultured in an osteogenic induction medium. In addition to checking the expression of genes related to bone formation, we also investigated the expression of several genes related to immunomodulation at the mRNA level. We observed that LiCl enhanced the osteogenesis of Ad-MSCs, as evidenced by an increase in mineralization and the enhanced expression of osteogenic markers. Moreover, the expression of cytokines, which promote the anti-inflammatory behavior of these cells, was augmented. These findings could potentially be clinically relevant to improving conditions associated with bone loss, such as osteopenia and osteoporosis.
Sepideh sadat Hosseini; Shadi Mehrzad; Halimeh Hassanzadeh; Hamid Reza Bidkhori; Mahdi Mirahmadi; Madjid Momeni-Moghaddam; Fatemeh Sadeghifar; Moein Farshchian
Abstract
Mesenchymal stem/stromal cells (MSCs) as one of the most important types of adult stem cells secrete a variety of immunomodulatory cytokines. However, their immunomodulatory features strongly depend on the molecular cross-talk between cells and the surrounding microenvironment. Hence, ...
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Mesenchymal stem/stromal cells (MSCs) as one of the most important types of adult stem cells secrete a variety of immunomodulatory cytokines. However, their immunomodulatory features strongly depend on the molecular cross-talk between cells and the surrounding microenvironment. Hence, some strategies were proposed to empower their beneficial effects during cell-therapeutic procedures to avoid confusing results. Licensing the cells with chemical compounds could be considered as one of the most applicable methods for induction of anti-inflammatory status in the cells. Human chorionic gonadotropin (hCG) is a pregnancy related hormone which has been shown to be essential for the establishment of a successful pregnancy. HCG supports the implantation of fetus in the maternal endometrium, due to its immunomodulatory effects. Moreover, the regulatory role of hCG has been previously mentioned in case of some autoimmune-based diseases. In the present study, the capacity of this hormone for induction of different immune-encountered genes expression was examined in primary cultures of human adipose tissue derived mesenchymal stem cells (Ad-MSCs). In this regard, Ad-MSCs were exposed to 10 IU of hCG for 72 hours. Molecular studies via quantitative Real-time PCR (qRT-PCR) experiments were performed to detect gene expression modifications based on the application of SYBR Green as the fluorescent dye and in comparison to the RPLP0 as the housekeeping gene. Results confirmed that hCG significantly upregulated TSG-6, TGF-β1, IL-1β and IL-6 expression levels comparing with the control group, while it downregulates COX-2 expression, and had no statistically significant effects on IL-10 andTDO2. In conclusion, priming Ad-MSCs with hCG may enhance the proliferation and immunoregulatory potential of these cells, although it needs further investigations to reveal involved molecular pathways.
Shadi Mehrzad; Sepideh sadat Hosseini; Madjid Momeni-Moghaddam; Moien Farshchian; Halimeh Hassanzadeh; Mahdi Mirahmadi; Fatemeh Sadeghifar; Hamid Reza Bidkhori
Abstract
Oxidative stress occurs as a result of breaking down the balance between oxidants (e.g., reactive oxygen species (ROS)) and antioxidants in cells. Several studies have shown that there is a close relationship between oxidative stress and inflammation at the sites of injury. Mesenchymal ...
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Oxidative stress occurs as a result of breaking down the balance between oxidants (e.g., reactive oxygen species (ROS)) and antioxidants in cells. Several studies have shown that there is a close relationship between oxidative stress and inflammation at the sites of injury. Mesenchymal stem cells (MSCs) are exposed to endogenous and exogenous oxidants generated during their ex vivo expansion or following in vivo transplantation. α-tocopherol (vitamin E) is a fat-soluble compound known for its anti-oxidant and anti-inflammatory properties. In many studies, the immunomodulatory effects of vitamin E have been observed in vivo. This study aimed to determine whether pretreatment of MSCs with antioxidants like vitamin E, will enhance the anti-inflammatory and immunomodulatory properties of these cells. For this purpose, adipose-derived MSCs (ASCs) were treated with vitamin E (600 μM) for 48 h. Quantitative PCR (qPCR) experiments were performed to evaluate the expression of genes related to inflammation (IL-1β, IL-6, IL-17, IL-10) or immunomodulation (TSG-6, COX-2, TDO2, TGF-β1). Results indicated that vitamin E significantly increased the expression of COX-2, TSG-6, and IL-1β genes at the mRNA level compared with the control group, while it significantly decreased IL-6 and TGF-β expressions. No effect was observed for IL-17, IL-10, and TDO2 genes. These results suggest that in vitro preconditioning of ASCs with vitamin E may allow the cells to improve their anti-inflammatory and immunoregulatory capacities. Vitamin E pretreatment could lead to the improvement of their therapeutic abilities in conditions that are influenced by oxidative stress.
