Zahra Fazeli

Mesenchymal Stem Cells (MSCs) Therapy for Recovery of Fertility: a Systematic Review

In recent years, the mesenchymal stem cells (MSCs) have provided the new opportunities to treat different disorders including infertility. Different studies have suggested that the MSCs have ability to differentiate into germ-like cells under specific induction conditions as well as transplantation to gonadal tissues. The aim of this systematic review was to evaluate the results obtained from different studies on MSCs therapy for promoting fertility. This search was done in PubMed and Science Direct databases using key words MSCs, infertility, therapy, germ cell, azoospermia, ovarian failure and mesenchymal stem cell. Among the more than 11,400 papers, 53 studies were considered eligible for more evaluations. The obtained results indicated that the most studies were performed on MSCs derived from bone marrow and umbilical cord as compared with the other types of MSCs. Different evaluations on animal models as well as in vitro studies supported from their role in the recovery of spermatogenesis and folliculogenesis. Although the data obtained from this systematic review are promising, but the further studies need to assess the efficiency and safety of transplantation of these cells in fertility recovery.

CD29/CD184 expression analysis provides a signature for identification of neuronal like cells differentiated from PBMSCs

In vitro study was used as a helpful model to investigate the role of different growth factors in differentiation of stem cells. The aim of this study was to find an easy and robust method for confirmation of Peripheral Blood-Mesenchymal Stem Cells (PB-MSCs) differentiation into neuronal cells. A set of CD markers as well as neural markers were used to elucidate their differentiation. In the present study, PB-MSCs were isolated by density centrifugation. Isolated cells were divided into four groups: (i) untreated PB-MSCs as control cells, (ii) cells treated with 50ng/ml Noggin [N50], (iii) cells treated with 75ng/ml Noggin [N75], (iv) cells treated with 100ng/ml Noggin [N100]. These cells were cultured for 14days. Expression of CD24, CD29 and CD184 markers was evaluated by flow cytometry. Furthermore, the neural markers as well as BMP genes expression were analyzed by Real time PCR. Our in vitro studies demonstrated that Noggin had diverse effects on neural differentiation of PB-MSCs depending on the concentration. N75 treatment induced neuronal differentiation of PB-MSCs more strongly than N50 treatment. Furthermore, differentiation of PB-MSCs into neuronal lineage was inhibited by N100 treatment. Our result showed that exposure of PB-MSCs to Noggin with 75ng/ml concentration was associated with changes in pattern of CD29/CD184 expression. The expression profile of CD29(+/-)/CD184(-) can be suggested as a robust signature for tracing differentiation of Peripheral Blood-Mesenchymal Stem Cells (PB-MSCs) into neuronal cells.

Molecular phylogenetic study of the Iranians based on polymorphic markers

The application of polymorphic markers in construction of phylogenetic trees has been documented. Five polymorphic markers located in the PAH gene region including PAH-BglII, PAH-PvuII(A), PAH-EcoRI, PAH-MspI and PAH-STR were selected for analysis of phylogenetic relationships of the Iranians with 15 other populations of the world. The lowest genetic distance was observed between the Iranians and populations residing in Adygei (an ethnic group of the Russian Caucasus), Russia and Druze (a Middle Eastern group). However, East Asian populations including Han, Japanese and Cambodians, Khmer or the Oceanians (Melanesian, Nasioi) showed high genetic distance with the Iranians. The data suggested that the Iranians might have relatively close evolutionary history with the populations residing in Russia rather than East Asian populations. This study provided the first new molecular insight into the evolutionary history of the Iranian population.

Phylogenetic relationship analysis of Iranians and other world populations using allele frequencies at 12 polymorphic markers

The estimation of genetic distance between populations could improve our viewpoint about human migration and its genetic origin. In this study, we used allele frequency data of 12 polymorphic markers on 250 individuals (500 alleles) from the Iranian population to estimate genetic distance between the Iranians and other world populations. The phylogenetic trees for three different sets of allele frequency data were constructed. Our results revealed the genetic similarity between the Iranians and European populations. The lowest genetic distance was observed between the Iranians and some populations reside in Russia. Furthermore, the high genetic distance was observed between the Iranians and East Asian populations. The data suggested that the Iranians might have relatively close evolutionary history with Europeans, but historically independent from East Asian populations. The evaluation of genetic distance between Indians populations and Iranians was also performed. The Indian groups showed low genetic distance with others, but high genetic distance with the Iranians. This study could provide a new insight into the evolutionary history of the Iranian population.

High expression of miR-510 was associated with CGG expansion located at upstream of FMR1 into full mutation: FAZELI et al.

MicroRNAs (miRNAs) have been found to play an important role in the regulation of gene expression in eukaryotic organisms at the posttranscriptional level. More than half of miRNA genes have been recognized to be located in different fragile sites. Among them, miR‐510 was located on chromosome X in the 27.3Xq region, flanking to a fragile X site. The CGG expansion and its methylation at the promoter of FMR1 located in this fragile site were associated with clinical symptoms of fragile X syndrome (FXS). The aim of the current study was to investigate whether the miR‐510 expression was correlated with the CGG expansion of FMR1 in female carriers of full mutation. For this purpose, mesenchymal stem cells were isolated from peripheral blood of FMR1 full mutation female carriers. After differentiation of these cells into neuronal cells, the expression of miR‐510 was analyzed by quantitative polymerase chain reaction. Furthermore, the target genes of miR‐510 in the nervous system were also predicted by in silico method. The obtained results indicated that the CGG expansion of FMR1 was associated with the enhanced expression of miR‐510. Furthermore, the bioinformatics analysis suggested that VHL and PPP2R5E genes could be considered as the most important target genes of miR‐510 in the nervous system. This study showed that miR‐510 and its target genes, specifically VHL and PPP2R5E, may represent the new targets for future therapy options of FXS.

Association between Long Noncoding RNA ANRIL Expression Variants and Susceptibility to Coronary Artery Disease

Animal cells possess thousands of long non-coding (lnc) RNAs, such as antisense noncoding RNA in the INK4 locus (ANRIL), which have regulatory roles in the cells’ molecular mechanisms, including X-chromosome inactivation, and developmental processes. These lnc RNAs are known to influence the extensive spectrum of age-related disorders. Accordingly, there is evidence for the role of these lnc RNAs in cardiovascular diseases, particularly coronary artery diseases (CAD). The aim of this study was to assess whether the expression of the lnc RNA ANRIL was associated with a susceptibility to CAD by evaluating the expression level of the two transcripts of ANRIL. Peripheral blood was taken from fifty patients affected by CAD and relative expression of ANRIL was determined by Real-Time PCR assay. The obtained data indicated that the EU741058 transcript expression level significantly decreased in CAD patients in comparison with the healthy individuals (P= 0.001). Furthermore, there was no significant association between the NR_003529 transcript expression, and CAD risk in Iranian patients (P=0.751). Our results suggest that the expression level of the EU741058 transcript of ANRIL may be implicated in CAD development, creating a predictive biomarker for CAD patients in future.