Definition and history of stem cell Stem cells are one of the main cells of the human body that have ability to grow more than 200 types of body cells (1). Stem cells, as non-specialized cells, can be transformed into highly specialized cells in the body (2). In the other words, Stem cells are undifferentiated cells with self-renewal potential, differentiation into several types of cells and excessive proliferation (3). In the past, it was believed that stem cells can only differentiate into mature cells of the same organ. Today, there are many evidences to show that stem cells can differentiate into the other types of cell as well as ectoderm, mesoderm and endoderm. The numbers of stem cells are different in the tissues such as bone marrow, liver, heart, kidney, and etc. (3,4). Over the past 20 years, much attention has been paid to stem cell biology. Therefore, there was a profound increase in the understanding of its characteristics and the therapeutic potential for its application (5). Today, the utilization of these cells in experimental research and cell therapy represents in such disorders including hematological, skin regeneration and heart disease in both human and veterinary medicine (6).The history of stem cells dates back to the 1960s, when Friedenstein and colleagues isolated, cultured and differentiated to osteogenic cell lineage of bone marrow-derived cells from guinea pigs (7). This project created a new perspective on stem cell research. In the following, other researchers discovered that the bone marrow contains fibroblastlike cells with congenic potential in vitro, which were

Mesenchymal stem cells (MSCs) are of particular interest because of their potential in regenerative medicine. Stem cell-based therapies cast a new hope for neurodegenerative disease treatment as a regeneration strategy, including treatment for Alzheimer's disease (AD). A multitude of cytokines and factors secreted from MSCs are known to give such multifunctional properties, but associated mechanisms of these factors have yet to be entirely understood. To better understand the in vitro effect of MSCs on a neurodegenerative disorder, we treated primary cortical and hippocampal neural cells with amyloid β (Aβ) as an in vitro cell line model for AD. For this purpose, bone marrow-derived MSCs (BMSCs) were cocultured with Aβ-treated neural cells, collected at day 3, and subjected to absolute telomere length measurement and telomerase activity assay. Next, the gene and protein expression levels of mTOR, p-mTOR, AMPK, p-AMPK, GSK-3β, p-GSK-3β, Wnt3, and β-catenin were investigated. Also, after 3 days of coculture treatment, the supernatant was collected from both groups for cytokine measurement. It was found that telomere length as a biomarker in neurodegenerative disorder as well as telomerase activity had significantly increased in the experimental group, and the presence of IL-6, IL-10, and TGF-β was obviously significant in the cocultured media. Also, BMSCs significantly changed the gene and protein expression of mTOR, AMPK, GSK-3β, and Wnt3/βcatenin signaling pathways components. It was concluded that the mentioned effects of MSCs on neural cells as an in vitro cell line model for AD as a therapeutic agent can be related to the signaling network.

Mesenchymal stem cells (MSCs) are of special interest due their potential clinical use in cell-based therapy. Therapies engaging MSCs are showing increasing promise in the cancer treatment and anticancer drug screening applications. A multitude of growth factors and cytokines secreted from these cells are known to give such multifunctional properties, but details of their role are yet to be absolutely demonstrated. In this study, we have evaluated the influence of BMSCs on K562 cell line as chronic myeloid leukemia (CML) cells, with the use of a cytokine antibody array recognizing 34 cytokines. For this purpose, BMSCs were isolated and co-cultured with K562 cells; thereafter, cultured K562 alone and co-cultured K562 with BMSCs (10:1) were collected at day 7 and subjected to cell cycle distribution assay as well as annexin/PI analysis and Ki/caspase-3 assay for apoptosis assessment. In the following, the gene and protein expression levels of BAX and BCL-2 as pro- and anti-apoptotic agents were investigated. Furthermore, after 7 days’ treatment, culture medium was collected from both control and experimental groups for cytokine antibody array. It was found that BMSCs resulted in a robust increase in the number of cells at G 0 /G 1 phase and arrest the G 0 /G 1 phase as well as significantly inducing late apoptosis in K562 cells. The significant presence of TIMP-1 (tissue inhibitor of metalloproteinases-1), and moderate elevated signals for CINC-1 (cytokine-induced neutrophil chemoattractant-1) were obvious in the co-cultured conditioned media, but no significant increase was found in 32 other cytokines. It is concluded that co-culture of BMSCs with K562 cells could secrete a substantial amount of TIMP-1 and CINC-1. These cytokines could be involved in the inhibition of the K562 cell proliferation via BAX and caspase-3 cascade pathways.

Zinc ion as an essential trace element and electromagnetic fields (EMFs) has been reported to be involved in the regulation of bone metabolism. The aim of this study was to elucidate the effects of zinc sulphate (ZnSO4) on the osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs) in the presence of EMF as a strategy in osteoporosis therapy. Alkaline phophatase (ALP) activity measurement, calcium assay and expression of several osteoblastic marker genes were examined to assess the effect of ZnSO4 on the osteogenic differentiation of ADSCs under EMF. The expression of cAMP and PKA was evaluated by ELISA. The expression of β-catenin, Wnt1, Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5) and reduced dickkopf1 (DKK1) genes were used to detect the Wnt/β-catenin pathway. It was found that ZnSO4, in the presence of EMF, resulted in an increase in the expression of osteogenic genes, ALP activity and calcium levels. EMF, in the presence of ZnSO4, increased the cAMP level and protein kinase A (PKA) activity. Treatment of ADSCs with (MAPK)/ERK kinase 1/2 inhibitor, or PKA inhibitor, significantly inhibited the promotion of osteogenic markers, indicating that the induction of osteogenesis was dependent on the ERK and PKA signaling pathways. Real-time PCR analysis showed that ZnSO4, in the presence of EMF, increased the mRNA expressions of β-catenin, Wnt1, Wnt3a, LRP5 and DKK1. In this study, it was shown that 0.432 μg/ml ZnSO4, in the presence of 50 Hz, 20 mT EMF, induced the osteogenic differentiation of ADSCs via PKA, ERK1/2 and Wnt/β-catenin signaling pathways.

Drug resistance in cancer, especially in leukemia, creates a dilemma in treatment planning. Consequently, studies related to the mechanisms underlying drug resistance, the molecular pathways involved in this phenomenon, and alternate therapies have attracted the attention of researchers. Among a variety of therapeutic modalities, mesenchymal stem cells (MSCs) are of special interest due to their potential clinical use. Therapies involving MSCs are showing increasing promise in cancer treatment and anticancer drug screening applications; however, results have been inconclusive, possibly due to the heterogeneity of MSC populations. Most recently, the effect of MSCs on different types of cancer, such as hematologic malignancies, their mechanisms, sources of MSCs, and its advantages and disadvantages have been discussed. There are many proposed mechanisms describing the effects of MSCs in hematologic malignancies; however, the most commonly-accepted mechanism is that MSCs induce tumor cell cycle arrest. This review explains the anti-tumorigenic effects of MSCs through the suppression of tumor cell proliferation in hematological malignancies, especially in acute myeloid leukemia.

The use of mesenchymal stem cells (MSCs) for cell therapy and regenerative medicine has received widespread attention over the past few years, but their application can be complicated by factors such as reduction in proliferation potential, the senescent tendency of the MSCs upon expansion and their age-dependent decline in number and function. It was shown that all the mentioned features were accompanied by a reduction in telomerase activity and telomere shortening. Furthermore, the role of epigenetic changes in aging, especially changes in promoter methylation, was reported. In this study, MSCs were isolated from the adipose tissue with enzymatic digestion. In addition, immunocytochemistry staining and flow cytometric analysis were performed to investigate the cell-surface markers. In addition, alizarin red-S, sudan III, toluidine blue, and cresyl violet staining were performed to evaluate the multi-lineage differentiation of hADSCs. In order to improve the effective application of MSCs, these cells were treated with 1.5 × 10−8 and 2.99 × 10−10 M of ZnSO4 for 48 hours. The length of the absolute telomere, human telomerase reverse transcriptase (hTERT) gene expression, telomerase activity, the investigation of methylation status of the hTERT gene promoter and the percentage of senescent cells were analyzed with quantitative real-time PCR, PCR-ELISA TRAP assay, methylation specific PCR (MSP), and beta-galactosidase (SA-β-gal) staining, respectively. The results showed that the telomere length, the hTERT gene expression, and the telomerase activity had significantly increased. In addition, the percentage of senescent cells had significantly decreased and changes in the methylation status of the CpG islands in the hTERT promoter region under treatment with ZnSO4 were seen. In conclusion, it seems that ZnSO4 as a proper antioxidant could improve the aging-related features due to lengthening of the telomeres, increasing the telomerase gene expression, telomerase activity, decreasing aging, and changing the methylation status of hTERT promoter; it could potentially beneficial for enhancing the application of aged-MSCs.

Aging and losing cell survival is one of the main problems in cell therapy. Aging of Mesenchymal Stem Cells (MSCs) is associated with a rise in intracellular reactive oxygen species, decrease in telomerase reverse transcriptase (TERT) expression and finally eroded telomere ends. Given that the production of free radicals in the aging process is effective, the use of antioxidants can help in scavenging free radicals and prevent the aging of cells. The aim of this study is to evaluate the effects of curcumin on proliferation, aging and TERT expression of rat adipose tissue-derived stem cells (rADSC). rADSCs were isolated from inguinal rat adipose tissue and their viabilities were assessed by MTT after exposure to different concentrations of curcumin. Flow-cytometry was performed for investigating the cell surface markers. Adipogenic and osteogenic differentiation were carried out to evaluate the pluripotency of rADSCs. Telomerase expression and percentage of senescent cells were evaluated using real-time PCR and senescence-associated β-galactosidase activity, respectively. The results demonstrated significant proliferation of rADSCs after 48 h treatment with 1 and 5 µM curcumin. Additionally, these concentrations could significantly reduce the population doubling time and aging of rADSCs at different passages. The findings of SA-ß-gal staining showed that curcumin significantly decreased the number of senescent cells in the 5 and 7 cell passages. Moreover, expression levels of TERT increased in the presence of 1 and 5 µM curcumin than control group (P<0.001). As a conclusion, curcumin may be a good candidate to improve lifespan of rADSCs through promoting TERT gene expression.

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