Cell Journal (Yakhteh)
Year:2016 | Volume:18 | Issue:2 (70)|Papers Count:19

Ageing is a complex process and a broad spectrum of physical, psychological, and social changes over time. Accompanying diseases and disabilities, which can interfere with cancer treatment and recovery, occur in old ages. MicroRNAs (miRNAs) are a set of small non-coding RNAs, which have considerable roles in post-transcriptional regulation at gene expression level. In this review, we attempted to summarize the current knowledge of miRNAs functions in ageing, with mainly focuses on malignancies and all underlying genetic, molecular and epigenetics mechanisms. The evidences indicated the complex and dynamic nature of miRNA-based linkage of ageing and cancer at genomics and epigenomics levels which might be generally crucial for understanding the mechanisms of age-related cancer and ageing. Recently in the field of cancer and ageing, scientists claimed that uric acid can be used to regulate reactive oxygen species (ROS), leading to cancer and ageing prevention; these findings highlight the role of miRNA-based inhibition of the SLC2A9 antioxidant pathway in cancer, as a novel way to kill malignant cells, while a patient is fighting with cancer.

Objective: Lactobacilli are a group of probiotics with beneficial effects on prevention of cancer. However, there is scant data in relation with the impacts of probiotics in late-stage cancer progration, especially metastasis. The present original work was aimed to evaluate the anti-metastatic and anti-proliferative activity oflactobacillus rhamnosus supernatant (LRS) andlactobacillus crispatus supernatant (LCS) on the human cervical and colon adenocarcinoma cell lines (HeLa and HT-29, respectively).Materials and Methods: In this experimental study, the anti-proliferative activities of LRS and LCS were determined through MTT assay. MRC-5 was used as a normal cell line.Expression analysis ofCASP3, MMP2, MMP9, TIMP1 and TIMP2 genes was performed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), following the cell synchronization.Results: Supernatants of these two lactobacilli had cytotoxic effect on HeLa, however LRS treatment was only effective on HT-29 cell line. In addition, LRS had no side-effect on normal cells. It was shown thatCASP3 gene expression has been reduced after treatment with supernatants of two studied lactobacilli. According to our study, LRS and LCS are efficacious in the prevention of metastasis potency in HeLa cells with decreased expression ofMMP2, MMP9 and increased expression of their inhibitors. In the case of HT-29 cells, only LRS showed this effect.Conclusion: Herein, we have demonstrated two probiotics which have anti-metastatic effects on malignant cells and they can be administrated to postpone late-stage of cancer disease. LRS and LCS are effective on HeLa cell lines while only the effect of LRS is significant on HT-29, through cytotoxic and anti-metastatic mechanisms. Further assessments are required to evaluate our results on the other cancer cell lines, in advance to use these probiotics in other extensive trial studies.

Objective: This study aimed to evaluate a co-encapsulated pegylated nano-liposome system based on two herbal anti-tumor drugs, silibinin and glycyrrhizic acid, for delivery to a hepatocellular carcinoma (HCC) cell line (HepG2).Materials and Methods: In this experimental study, co-encapsulated nano-liposomes by the thin layer film hydration method with HEPES buffer and sonication at 60% amplitude.Liposomes that co-encapsulated silibinin and glycyrrhizic acid were prepared with a specified molar ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol (CHOL), and methoxy-polyethylene glycol 2000 (PEG2000) –derived distearoyl phosphatidylethanolamine (mPEG2000-DSPE). We used the MTT technique to assess cytotoxicity for various concentrations of co-encapsulated nano-liposomes, free silibinin (25% w/v) and glycyrrhizic acid (75% w/v) on HepG2 and fibroblast cell lines over a 48-hour period.Results: Formulation of pegylated nano-liposomes showed a narrow size distribution with an average diameter of 46.3 nm. The encapsulation efficiency (EE) for silibinin was 24.37%, whereas for glycyrrhizic acid it was 68.78%. Results ofin vitro cytotoxicity showed significantly greater co-encapsulated nano-liposomes on the HepG2 cell line compared to the fibroblast cell line. The half maximal inhibitory concentration (IC50) for co-encapsulated pegylated nanoliposomal herbal drugs was 48.68 mg/ml and free silibinin with glycyrrhizic acid was 485.45 mg/ml on the HepG2 cell line.Conclusion: This in vitro study showed that nano-liposome encapsulation of silibinin with glycyrrhizic acid increased the biological activity of free drugs, increased the stability of silibinin, and synergized the therapeutic effect of silibinin with glycyrrhizic acid. The IC50 of the co-encapsulated nano-liposomes was lower than the combination of free silibinin and glycyrrhizic acid on the HepG2 cell line.

Objective: Gastric cancer is a major health issue worldwide. Using a therapeutic approach, with minor side-effects, is very essential for the treatment of the gastric cancer.Shiraia bambusicolais a parasitic fungus which is widely used in China for curing several diseases with little side-effects. However, the mechanisms are not well understood yet.The aim of this study was to further understand the pharmacological mechanisms ofShiraia bambusicolaand investigate whether it can be used for curing gastric cancer.Materials and Methods: In this experimental study, we mainly tested the effect of active components extracted fromShiraia bambusicola on BGC823, A549 and HepG2 cells. We used MTT assay to test cell viability. We also analyzed morphologic changes caused by apoptosis using Hoechst 33342 fluorescence staining, as well as cell cycle status and apoptosis ratio using flow-cytometer. In addition, protein expression level was tested by Western-blotting assay.Results: BGC-823 cell proliferation was specifically inhibited by active components of Shiraia bambusicola. Meanwhile, these active components could induce BGC-823 cells apoptosis and retard the cell cycle in S/G2 phase. We also determined that two critical protein markers cleaved Poly (ADP-ribose) polymerase-1 (PARP-1) and FLICE-inhibitory protein (FLIP), involved in apoptosis process, were regulated by these active components.Conclusion: These data shed light on the treatment of human gastric cancer and conclude thatShiraia bambusicola can be a good therapeutic candidate for treatment of this malignancy.

Objective: Signaling pathways such as extracellular regulated kinase/mitogen activated protein kinase (ERK/MAPK) have increased activity in leukemia. Ribosomal 6 kinase (RSK4) is a factor downstream of the MAPK/ERK pathway and an important tumor suppressor which inhibits ERK trafficking. Decrease inRSK4 expression has been reported in some malignancies, which leads to an increase in growth and proliferation and eventually poor prognosis. In this study we measuredRSK4 expression rate in acute myeloid leukemia (AML).Materials and Methods: This cross-sectional study was undertaken in 2013-2014 at Ghaem Hospital in Mashhad, Iran, on 40 AML patients and 10 non-AML patients as the control group. The expression rate was measured by real-time polymerase change reaction (PCR) and employing the DDCT method. Data were analyzed using Mann-Whitney and Spearman tests using SPSS (version 11.5).Results: Expression rate of RSK4 was significantly decreased in the AML group in comparison with the non-AML group (P<0.001). There was also a significant decrease in RSK4expression in AML with t (15; 17) in comparison to other translocations (P=0.004).Conclusion: We detected a down-regulation of RSK4 in AML patients. This may lead to an increase in the activity of the ERK/MPAK pathway and exacerbate leukemogenesis or the prognosis of the patients.

Objective: MicroRNAs (miRNAs) are small endogenous non-coding regulatory RNAs that control mRNAs post-transcriptionally. Several mouse stem cells miRNAs are cloned differentially regulated in different hematopoietic lineages, suggesting their possible role in hematopoietic lineage differentiation. Recent studies have shown that specific miRNAs such asMir-451 have key roles in erythropoiesis.Materials and Methods: In this experimental study, murine embryonic stem cells (mESCs) were infected with lentiviruses containingpCDH-Mir-451. Erythroid differentiation was assessed based on the expression level of transcriptional factors (Gata-1, Klf-1, Epor) and hemoglobin chains (a, b, g, e and  ζ) genes using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and presence of erythroid surface antigens (TER-119 and CD235a) using flow cytometery. Colony-forming unit (CFU) assay was also on days 14th and 21th after transduction.Results: Mature Mir-451 expression level increased by 3.434-fold relative to the untreated mESCs on day 4 after transduction (P<0.001).Mir-451 up-regulation correlated with the induction of transcriptional factor (Gata-1, Klf-1, Epor) and hemoglobin chain (a, b, g, e and  ζ) genes in mESCs (P<0.001) and also showed a strong correlation with presence of CD235a and Ter-119 markers in these cells (13.084- and 13.327-fold increse, respectively) (P<0.05). Moreover, mESCs treated with pCDH-Mir-451showed a significant raise in CFU-erythroid (CFU-E) colonies (5.2-fold) compared with untreated control group (P<0.05).Conclusion: Our results showed that Mir-451 up-regulation strongly induces erythroid differentiation and maturation of mESCs. Overexpression ofMir-451 may have the potential to produce artificial red blood cells (RBCs) without the presence of any stimulatory cytokines.

Objective: In vivo and in vitro stem cell differentiation into endothelial cells is a promising area of research for tissue engineering and cell therapy.Materials and Methods: We induced human mesenchymal stem cells (MSCs) to differentiate to endothelial cells that had the ability to form capillaries on an extracellular matrix (ECM) gel. Thereafter, the differentiated endothelial cells at early stage were characterized by expression of specific markers such as von Willebrand factor (vWF), vascular endothelial growth factor (VEGF) receptor 2, and CD31. In this experimental model, the endothelial cells were transplanted into the groins of severe combined immunodeficiency (SCID) mice.After 30 days, we obtained tissue biopsies from the transplantation sites. Biopsies were processed for histopathological and double immunohistochemistry (DIHC) staining.Results: Endothelial cells at the early stage of differentiation expressed endothelial markers.Hematoxylin and eosin (H& E) staining, in addition to DIHC demonstrated homing of the endothelial cells that underwent vascularization in the injected site.Conclusion: The data clearly showed that endothelial cells at the early stage of differentiation underwent neovascularizationin vivo in SCID mice. Endothelial cells at their early stage of differentiation have been proven to be efficient for treatment of diseases with impaired vasculogenesis.

Objective: Treatment and repair of neurodegenerative diseases such as brain tumors, spinal cord injuries, and functional disorders, including Alzheimer’s disease, are challenging problems. A common treatment approach for such disorders involves the use of mesenchymal stem cells (MSCs) as an alternative cell source to replace injured cells.However, use of these cells in hosts may potentially cause adverse outcomes such as tumorigenesis and uncontrolled differentiation. In attempt to generate mesenchymal derived neural cells, we have infected MSCs with recombinant lentiviruses that expressed nerve growth factor (NGF) and assessed their neural lineage genes.Materials and Methods: In this experimental study, we cloned the NGF gene sequence into a helper dependent lentiviral vector that contained the green fluorescent protein(GFP) gene. The recombinant vector was amplified in DH5 bacterial cells. Recombinant viruses were generated in the human embryonic kidney 293 (HEK-293) packaging cell line with the helper vectors and analyzed under fluorescent microscopy. Bone marrow mesenchymal cells were infected by recombinant viruses for three days followed by assessment of neural differentiation. We evaluated expression of NGF through measurement of the NGF protein in culture medium by ELISA; neural specific genes were quantified by real-time polymerase chain reaction (PCR).Results: We observed neural morphological changes after three days. Quantitative PCR showed that expressions ofNESTIN, glial derived neurotrophic factor (GDNF), glial fibrillary acidic protein(GFAP) and Microtubule-associated protein 2 (MAP2) genes increased following induction of NGF overexpression, whereas expressions of endogenous NGF and brain derived neural growth factor(BDNF) genes reduced.Conclusion: Ectopic expression of NGF can induce neurogenesis in MSCs. Direct injection of MSCs may cause tumorigenesis and an undesirable outcome. Therefore an alternative choice to overcome this obstacle may be the utilization of differentiated neural stem cells.

Objective: Annexin A1 (ANXA1) is suggested to have anti-inflammatory function. However, the precise function of ANXA1 has remained unclear. In this study, we therefore examined the potency of ANXA1 in regulating reactive oxygen species (ROS) production and suppressing pro-inflammatory responses in PC12 cells induced by 1-methyl-4-phenylpyridinium (MPP+).Materials and Methods: In this experimental study, cDNA of ANXA1 was cloned and inserted to the PGL268 pEpi-FGM18F vector to produce a recombinant PGL/ANXA1 vector for transfection into the PC12 cells. ANXA1 transfected cells were then treated with MPP+. Apoptosis and the content of pro-inflammatory factors including ROS, Interlukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-kB) were assessed by flow-cytometry, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in ANXA1-transfected cells and the data were compared with those obtained from mock and control cells.Results: Data revealed that overexpression of ANXA1 is associated with decreased levels of ROS and expression level of IL-6 and iNOS transcripts, and NF-kB protein in MPP+ treated PC12 cells.Conclusion: ANXA1 may be considered as an agent for prevention of neurodegenerative or inflammatory conditions.

Objective: In conventional assisted reproductive technology (ART), oocytes are cultured in static microdrops within Petri dishes that contain vast amounts of media. However, the in vivoenvironment is dynamic. This study assesses in vitro oocyte maturation through the use of a new microfluidic device. We evaluate oocyte fertilization to the blastocyct stage and their glutathione (GSH) contents in each experimental group.Materials and Methods: In this experimental study, we established a dynamic culture condition. Immature oocytes were harvested from ovaries of Naval Medical Research Institute (NMRI) mice. Oocytes were randomly placed in static (passive) and dynamic (active) in vitromaturation (IVM) culture medium for 24 hours. In vitro matured oocytes underwent fertilization, after which we placed the pronucleus (PN) stage embryos in microdrops and followed their developmental stages to blastocyst formation after 3 days. GSH content of thein vitro matured oocytes was assessed by monochlorobimane (MCB) staining.Results: We observed significantly higher percentages of mature metaphase II oocytes (MII) in the passive and active dynamic culture systems (DCS) compared to the static group (P<0.01). There were significantly less mean numbers of germinal vesicle (GV) and degenerated oocytes in the passive and active dynamic groups compared to the static group (P<0.01). Fertilization and blastocyst formation rate in the dynamic systems were statistically significant compared to the static cultures (P<0.01). There was significantly higher GSH content in dynamically matured oocytes compared to statically matured oocytes (P<0.01).Conclusion: Dynamic culture for in vitro oocyte maturation improves their developmental competency in comparison with static culture conditions.

Objective: Nuclear actin is involved in transcription regulation by recruitment of histone modifiers and chromatin remodelers to the regulatory regions of active genes. In recent years, further attention has been focused on the role of actin as a nuclear protein in transcriptional processes. In the current study, the epigenetic role of nuclear actin on transcription regulation of two stemness (OCT4 and NANOG) and two differentiation) NESTIN andPAX6) marker genes was evaluated in a human embryonal carcinoma cell line (NT2) before and after differentiation induction.Materials and Methods: In this experimental study, differentiation of embryonal cells was induced by retinoic acid (RA), and quantitative real-time polymerase chain reaction (PCR) was used to evaluate differential expression of marker genes before and 3 days after RAinduced differentiation. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR was then undertaken to monitor the incorporation of b-actin, as a functional component of RNA polymerase II, in the regulatory regions of marker genes.Results: Data showed significant change in nuclear actin incorporation into the promoter regions of NESTIN and PAX6 after RA-induction.Conclusion: We emphasize the dynamic functional role of nuclear actin in differentiation of embryonal cells and its role as a subunit of RNA polymerase II.

Objective: Peroxisome proliferator-activated receptor γ (PPARg) is a member of the PPAR nuclear receptor superfamily. Although PPARg acts as a master transcription factor in adipocyte differentiation, it is also associated with a variety of cell functions including carbohydrate and lipid metabolism, glucose homeostasis, cell proliferation and cell differentiation.This study aimed to assess the expression level of PPARg in order to address its role in cardiac cell differentiation of mouse embryonic stem cells (mESCs).Materials and Methods: In this an intervening study, mESCs were subjected to cardiac differentiation.Total RNA was extracted from the cells and quantitative real time polymerase chain reaction (qPCR) was carried out to estimate level of gene expression. Furthermore, the requirement of PPARg in cardiac differentiation of mESCs, during cardiac progenitor cells (CPCs) formation, was examined by applying the respective agonist and antagonist.Results: The obtained data revealed an elevation in the expression level of PPARg during spontaneous formation of CPCs and cardiomyocytes. Our results indicated that during CPC formation, PPARg inactivation via treatment with GW9662 (GW) reduced expression of CPC and cardiac markers.Conclusion: We conclude that PPARγ modulation has an effective role on cardiac differentiation of mESCs at the early stage of cardiomyogenesis.

Objective: The phenylalanine hydroxylase (PAH) locus has high linkage disequilibrium. Haplotypes related to this locus may thus be considered sufficiently informative for genetic diagnosis and carrier screening using multi-allelic markers. In this study, we present an efficient method for haplotype analysis of PAH locus using multiplexing dyes. In addition, we explain how to resolve the dye shift challenge in multiplex short tandem repeat (STR) genotyping.Materials and Methods: One hundred family trios were included in this descriptive study. The forward primer of a tetra-nucleotide STR and the reverse primer of a variable number tandem repeat (VNTR) were labeled with three different non-overlapping dyes 5-carboxyfluorescein (FAM), 6-carboxy-N, N, N’, N’-tetramethylrhodamine (HEX) and 6-carboxy-N, N, N’, N’-tetramethylrhodamine (TAMRA). The polymerase chain reaction (PCR) products from each family trio were multiplexed for capillary electrophoresis and results were analyzed using Peak Scanner software.Results: Multiplexing trio products decreased the cost significantly. The TAMRA labeled products had a significant predictable shift (migrated at a slower electrophoretic rate) relative to the HEX and FAM labeled products. Through our methodology we achieve, the less inter-dye shift than intra-dye shift variance. Correcting the dye shift in the labeled products, according to the reference allele size, significantly decreased the inter-dye variability (P<0.001).Conclusion: Multiplexing trio products helps to detect and resolve the dye shift accurately in each family, which otherwise would result in diagnostic error. The dye system of FAM, HEX and TAMRA is more feasible and cheaper than other dye systems.

Objective: Hypoxia-Inducible Factor (HIF) -1 plays an essential role in the body’s response to low oxygen concentrations and regulates expression of several genes implicated in homeostasis, vascularization, anaerobic metabolism as well as immunological responses. Increased levels of HIF-1a are associated with increased proliferation and more aggressive breast tumor development. Lactobacilli have been shown to exert anti-cancer effects on several malignancies including breast cancer. However, the exact mechanism of such effect is not clear yet.The aim of this study was to analyze the expression of selected genes from HIF pathway in a triple negative breast cancer cell line (expressing no estrogen and progesterone receptors as well as HER-2/Neu), MDA-MB-231, following treatment with two lactobacilli culture supernatants.Materials and Methods: In this experimental study, we analyzed the expression of HIF-1a, SLC2A1, VHL, HSP90, XBP1and SHARP1 genes from HIF pathway in MDA-MB-231 cells, before and after treatment withLactobacillus crispatus and Lactobacillus rhamnosus culture supernatants (LCS and LRS, respectively) by means of quantitative reverse-transcription polymerase chain reaction (qRT-PCR).Results: Both LRS and LCS had cytotoxic effects on MDA-MB-231 cells, while the former type was more cytotoxic. LRS dramatically down-regulated expression levels of theHIF-1a, HSP90and SLC2A1 in the MDA-MB-231 cells. LCS had similar effect on the expression ofHSP90, to what was observed in the LRS treatment. The expression level of tumor suppressor genesVHL and SHARP1 were also decreased in LCS treated cells.Conclusion: Although both LCS and LRS had cytotoxic effects on the MDA-MB-231 cells, it is proposed that LRS could be more appropriate for pathway directed treatment modalities, as it did not decrease expression of tumor suppressor genes involved in HIF pathway.Down-regulation of HIF pathway mediated oncogenes by LRS suggests that the cytotoxic effects of thislactobacillus may at least be partly caused by this mechanism. As previous studies have shown that inhibition of HIF-1a and HSP90 expressions have therapeutic impact on cancer treatment, the inhibitory effect of LRS on expression of these genes implies that thislactobacillus can be used in treatment strategies.

Objective: Thymoquinone (TQ), as the main component of Nigella Sativa plant, shows anticancer properties. This study was aimed to evaluate the combined effect of TQ and Tamoxifen (TAM) on viability and apoptosis of human breast cancer cell lines.Materials and Methods: In this experimental study, estrogen positive MCF-7 and estrogen negative MDA-MB-231 human breast cancer cell lines were induced by TAM (2 mM) or different doses of TQ (50, 75, 100, 150 mM), individually or in combination. Cell viability and apoptosis were investigated by MTT assay and TdT-mediated deoxy-uracil nick end labeling (TUNEL) assay; Acridine orange (AO) /Ethidium bromide (EB) staining respectively. Data were analyzed by one way ANOVA and P<0.05 was considered significant.Results: In 24 hours treatment, TAM and all doses of TQ, solely or in combination, significantly reduced cell viability of both cell lines, except in MCF-7 cells treated with 50 mM TQ, and MDA-MB-231 cells treated with 50 or 75 mM TQ (P<0.01). After 48 hours treatment, cell viability of both cell lines was reduced in all treated groups (P<0.05). Remarkable apoptotic index was observed in combination treatment of MCF-7 or MDA-MB-231 cell lines with TAM and TQ (P<0.001).Conclusion: The synergistic effect of TQ and TAM on human breast cancer cell lines showed cell viability reduction as well as apoptosis induction, independent to estrogen.

Objective: The genus Thymus L. is a cushion plant that was previously used for the treatment of bronchitis and rheumatism. The present investigation was carried out to study the effects of root, shoot, leaf and seed extracts of five Thymus species and subspecies on peripheral blood mononuclear cells (PBMCs) toxicity and HIV-1 replication.Materials and Methods: In this experimental study, the activity of the Thymus extracts on HIV-1 replication and lymphocytes population were examined respectively using HIV-1 p24 Antigen kit and flow-cytometer. The Thymus species effect was investigated, including Thymus kotschyanus, Thymus vulgaris, Thymus carmanicus, Thymus daenensissubspecies lancifoliusand Thymus daenensis subspecies daenensis.Results: The effect of root methanol extracts of all species on PBMCs proliferation was significantly higher than the other extracts. The intensity of CD4, CD3 and CD45 were decreased in the presence of all root extracts. Although the average median fluorescence intensity (MFI) values of CD19 were increased in the cells treated with these extracts. All methanol extracts showed anti-HIV-1 activity at high concentrations (200 and 500 mg/ml).Anti-HIV-1 activity ofThymus daenensis subspecies daenensis was significantly more than the other species.Conclusion: These results demonstrated that root extracts of Thymus species might be a good candidate to investigate anti-HIV infectionin vivo.

Objective: Although key roles for dietary vitamin E (VITE) and fatty acid (FA) in fertility have been confirmed, limited data are available on the effects of VITE alone, or a constant level of VITE supplemented by dietary omega-6 and omega-3 FAs in combination on male reproduction. Consequently in this paper, the effects of VITE, sunflower oil, fish oil and their combination on rat sperm were investigated.Materials and Methods: We divided 50 mature male Wistar rats into 5 groups (n=10) in a experimental completely randomized design for eight weeks: i. Control (CTR): standard diet; ii. Vitamin E diet (VITE): 2 times greater than recommendations; iii. Sunflower oil group (n-6) [gavaged with 0.5 ml/day/rat sunflower oil+VITE diet]; iv. Fish oil group (n-3): [gavaged with 0.5 ml/day/rat fish oil+VITE diet] and v. n-3+n-6 group [gavaged with 0.3 ml fish oil/day/rat+0.2 ml sunflower oil/day/rat+VITE diet]. The sperm parameters were measured by computer assisted semen analyzer (CASA). All data were analyzed with SPSS software.Results: Feed intake decreased in groups which were administered sunflower oil compared with the other groups (P<0.05). The groups which received only VITE or fish oil+VITE had a significantly higher concentration of sperm compared with the n- 6+n-3 and CTR group (P<0.05). VITE and n-3 showed significant improved progressive motility compared to the CTR group, whereas the n-6 and n-6+n-3 groups were in the middle (P<0.05). The highest sperm kinematic parameters were observed in the VITE only group. There was no strong correlation between sperm parameters and blood lipid profiles.Conclusion: Dietary VITE and fish oil+VITE can improve sperm quality. Our findings can be a focus for improvements in sperm quantity and motility in fertile animals using only dietary VITE.

Objective: Orthodontically induced inflammatory root resorption (OIIRR) is an undesirable sequel of tooth movement after sterile necrosis that takes place in periodontal ligament due to blockage of blood vessels following exertion of orthodontic force. This study sought to assess the effect of an angiogenic cytokine on OIIRR in rat model.Materials and Methods: In this experimental animal study, 50 rats were randomly divided into 5 groups of 10 each: E10, E100 and E1000 receiving an injection of 10, 100 and 1000 ng of basic fibroblast growth factor (bFGF), respectively, positive control group (CP) receiving an orthodontic appliance and injection of phosphate buffered saline (PBS) and the negative control group (CN) receiving only the anesthetic agent. A nickel titanium coil spring was placed between the first molar and the incisor on the right side of maxilla.Twenty-one days later, the rats were sacrificed. Histopathological sections were made to assess the number and area of resorption lacunae, number of blood vessels, osteoclasts and Howship’s lacunae. Data were statistically analyzed using ANOVA and Tukey’s honest significant difference (HSD) test.Results: Number of resorption lacunae and area of resorption lacunae in E1000 (0.97 ±0.80 and 1.27 ± 0.01×10-3, respectively) were significantly lower than in CP (4.17 ± 0.90 and 2.77 ± 0.01×10-3, respectively, P=0.000). Number of blood vessels, osteoclasts and Howship’s lacunae were significantly higher in E1000 compared to CP (P<0.05).Conclusion: Tooth movement as the outcome of bone remodeling is concomitant with the formation of sterile necrosis in the periodontal ligament following blocked blood supply.Thus, bFGF can significantly decrease the risk of root resorption by providing more oxygen and angiogenesis.

Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient’s life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies.