Mesenchymal Stem Cells: a Promising Therapeutic Tool for Acute Kidney Injury.

Acute kidney injury (AKI) is a rapid loss of renal function. It has high mortality rates. Still, renal replacement therapy is considered the best solution for recovering AKI. This opens a line of thought to develop an alternative therapy for it without complications. Mesenchymal stem cells are considered a new therapy for treating kidney diseases. The aim of this work was to address the anti-apoptotic, antioxidative, and pro-angiogenic effects of adipose tissue-derived MSCs (AD-MSCs) and bone marrow-MSCs (BM-MSCs) for treating AKI. Adult male Wistar rats were assigned into nine groups (n = 10): (1) the control group; (2) the AKI group, receiving cisplatin; (3) the AKI group treated with AD-MSCs (1 × 106); (4) the AKI group treated with AD-MSCs (2 × 106); (5) the AKI group treated with AD-MSCs (4 × 106); (6) the AKI group treated with losartan; (7) the AKI group treated with BM-MSCs (1 × 106); (8) the AKI group treated with BM-MSCs (2 × 106); and (9) the AKI group treated with BM-MSCs (4 × 106). The results showed a significant rise in creatinine, urea, and cystatin C (cys C) levels and upregulation of p38 mRNA, whereas a significant decline in NAD(P)H quinone oxidoreductase 1 (NQO-1) protein and downregulation of B-cell lymphoma-2 (Bcl-2) mRNA and vascular endothelial growth factor (VEGF) mRNA were recorded in AKI. MSCs could improve renal functions manifested by decreased urea, creatinine, and cys C levels; downregulation of p38; and upregulation of Bcl-2 and VEGF. Moreover, MSC therapy could induce NQO-1 in the treated rats relative to the untreated rats. So, cell-based therapy can reduce AKI through the antioxidative, anti-apoptotic, and pro-angiogenic properties of MSCs. Therefore, the findings received in this attempt create a fertile base for the setup of cell therapy in patients with AKI.

Therapeutic potential effect of bone marrow-derived mesenchymal stem cells on chronic liver disease in murine Schistosomiasis Mansoni.

Some reports have shown that mesenchymal stem cells (MSCs) therapy could ameliorate chemically-induced hepatic fibrosis. This research assesses the therapeutic action of bone marrow mesenchymal stem cells (BM-MSCs) on chronic diseased liver in Schistosoma mansoni infected mice. All infected female mice divided into three groups, one group (15 mice) treated with oral praziquantel (PZQ), second group (15 mice) received intravenous injection of BM-MSCs and third group (15 mice) treated with both MSCs + PZQ. Two control groups (15 mice each) subdivided into one infected and second healthy one. BM-MSCs were obtained from bones of both femur and tibia of male mice (30 mice), then cultured and characterized morphologically by detection of CD105 by flow cytometer. Liver tissues for all groups were examined histopathologically. Measuring of the collagen 1 gene expression was done by real-time PCR and immunohistochemical study to detect stem cells differentiation for detection of MSCs engraftments in liver tissue. MSCs treatment caused marked improvement and regression of fibrosis, and prevents deposition of collagen and reduced the expression of collagen 1 gene in infected mice on their liver tissues, especially when used with PZQ in mice treatment. It can be concluded that, MSCs is a good therapeutic method for liver fibrosis caused by S. mansoni infection.

Functional and Structural Assessment of the Effect of Human Umbilical Cord Blood Mesenchymal Stem Cells in Doxorubicin-Induced Cardiotoxicity.

Cardiomyopathy induced by doxorubicin (DOX) was recognized at an early stage and also several years after drug administration. Mesenchymal stem cells (MSCs) have many properties that make them suitable for preventive and/or regenerative therapies. In this study, we evaluated the effect of MSCs in the functional and the structural improvement of DOX-induced cardiomyopathy in rats. Ninety adult male albino rats were randomly divided into three equal groups of thirty rats each: Group I (control): rats received normal saline. Group II (DOX- group): rats received DOX. Group III (DOX-MSCs group): rats received DOX for 2 weeks then human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). Rats in all groups were evaluated for: physical condition, electrocardiography (ECG), and hemodynamic parameters. Serum cardiac troponin I (cTnI), malondialdehyde (MDA), total antioxidant capacity (TAC), and DNA fragmentation on heart tissue isolated DNA were estimated for evaluation of the mechanism and the extent of the damage. Hearts were examined histopathologically for detection of MSCs homing, structural evaluation, with counting of the collagen fibers for evaluation of fibrosis. DOX-administered rats showed significant functional and structural deterioration. DOX-MSCs treated rats (group III) showed improved functional and structural criteria with restoration of all biochemical indicators of cardiac damage and reactive oxygen species (ROS) to normal, as well. In Conclusion, hUCB-MSCs significantly ameliorated the cardiotoxic manifestations as shown by biochemical, functional, and structural cardiac improvement. J. Cell. Biochem. 118: 3119-3129, 2017. © 2017 Wiley Periodicals, Inc.

Murine hepatocytes DNA changes as an assessment of the immunogenicity of potential anti-schistosomal vaccines experimentally.

Hepatic affection by granulomatous inflammation in schistosomiasis suggested that a potential anti-pathology vaccine could be generated based on limiting the presence of hazardous hepatocytes induced apoptosis and caused reduction of granulomas number and size . So, this work is concerned with experimental assessment of the efficacy of different Schistosoma mansoni antigens (SEA, SWAP and combined SEA and SWAP) on murine liver after challenge by Schistosoma infection, histopathological, histochemical and molecular investigations were performed on sixty male laboratory bred Swiss Albino mice. A schedule of vaccination and challenge infection was followed and performed on 6 mice groups (each of ten); control normal (G1), control infected (G2), adjuvant received then infected (G3), SEA + adj. received then infected (G4), SWAP + adj. received then infected (G5) and SEA + SWAP + adj. received then infected (G6).Animals were euthanized 10 weeks post infection.Vaccination efficacy was assessed by histopathological, histochemical and molecular studies on murine hepatic tissues.Results showed that:The combined (SEA + SWAP) antigens were better in reducing the number and diameter of the hepatic granulomas, with more protection of the hepatocytes DNA, in addition to more decrease of hepatocytes induced apoptosis and fragmentation as demonstrated by molecular assay.

Factors enhancing the migration and the homing of mesenchymal stem cells in experimentally induced cardiotoxicity in rats.

Doxorubicin is an effective anti-neoplastic drug but its use is limited by its cardiotoxicity. Administration of mesenchymal stem cells (MSCs) for the management of cardiotoxicity was with poor myocardial homing capacity. With the aim of developing novel techniques to improve the migration of MSCs, we tested whether valproate and electric fields (EFs) direct the migration of MSCs towards the damaged myocardium. The study included five groups of female albino rats. The first group included 10 healthy rats as normal control group. The remaining 40 female rats received doxorubicin for induction of acute cardiotoxicity. Four rats were sacrificed for histopathological confirmation of cardiotoxicity. The remaining rats were equally divided into subsequent four groups. The second group included nine rats that did not receive further treatment (positive control group). The third group included nine rats which received intravenous bone marrow derived mesenchymal stem cells (BM-MSCs) after cardiotoxicity induction. The fourth group included nine rats which received BM-MSCs plus sodium valporate after cardiotoxicity induction. The fifth group included nine rats which received BM-MSCs plus sodium valporate after cardiotoxicity induction and were exposed to an electrical stimulation (ES). Blood samples were taken from all groups at the end of the study to estimate creatine kinase-MB (CK-MB), aspartate transaminase (AST) and lactate dehydrogenase (LDH). Heart tissues from all rats were used for RNA extraction for assessment of sry gene expression. Homing was tested by PKH26 fluorescence in myocardial tissue sections and by sry gene expression. The best biochemical and histopathological improvement in cardiotoxicity was demonstrated in group 5 (rats that received ES and valporate with MSCs). We concluded that EFs and sodium valproate enhance homing ability of MSCs towards the damaged myocardium in doxorubicin induced carditoxicity model. © 2017 IUBMB Life, 69(3):162-169, 2017.

Molecular effect of human umbilical cord blood CD34-positive and CD34-negative stem cells and their conjugate in azoospermic mice.

Currently, azoospermia is one of the most common diseases of male infertility. Stem cell research is the new hope for novel therapy with a higher degree of safety and lower cost. This study aimed to investigate the effect of umbilical cord blood-derived stem cells (" and mesenchymal "UCB-MSCs") and mono-cell layer implanted into the induced azoospermic mice testis. Stem cells were isolated from umbilical cord blood and CD34+ve cells were separated from negative one by Mini MACs column. At 5th week after single injection of busulfan, stained mesenchymal (CD34-ve), hematopoietic stem cells (CD34+ve) and their conjugate (mono-cell layer) were injected locally into testis. At the end of the study, MSCs group showed that mRNA levels of genes related to meiosis (Vasa, SCP3, and PgK2) were increased with significant decrease of FSH and LH levels, compared to control group. Histologically, most of the tubules restored normal architecture. In contrast, HSCs and mono-cell layer groups showed statically insignificant change of FSH, LH, and gene expression, compared to control group. Histologically, distorted seminiferous tubules, with reduction in sperm content, and interstitial mononuclear cellular infiltration were seen. There was significant increase in the optical density of PCNA immune reaction in MSCs group than azoospermia, HSCs, and mono-cell layer, while there was non-significant difference between MSCs and control group. The present study suggested that injection of MSCs into chemotherapeutic-induced azoospermia in mice improved testicular failure; histologically and functionally, by restoration of spermatogenic gene expression while HSC and mono-cell layer showed no effect on spermatogenesis added to that mono-cell layer may induce testicular tissue damage.

Breast milk MSCs: An explanation of tissue growth and maturation of offspring.

Exciting advances are revealing that breast milk harbors populations of stem and progenitor cells, and much attention is now intensified on delineating their properties and functions. The aim of this study is to isolate a mesenchymal stem cell (MSC)-like population from rabbit breast milk and track their integration into the different organs of the breastfed rabbits after taken by oral route and to explore the functional role of stem cells in the breastfed newborn babies. Ten newborn rabbits 2 weeks old fed on 2 × 106 PKH26-labeled rabbit milk derived-MSCs suspended in 2 mL Dulbecco's modified Eagle's medium (DMEM) and 10 newborn baby rabbits fed with 2 mL DMEM solution or with rabbit fibroblasts as a control group were used in the study. All rabbits were sacrificed after 1 week. We found that PKH26-labeled MSCs were engrafted into the offspring organs as liver, cartilage, bone and duodenum. Histologically, there was proliferation of cells in some organs. Moreover, there was overexpression of both PCNA and cyclin D1 genes in all organs from milk derived MSCs fed rabbits compared to the control group. Our results confirmed the presence of MSC-like population in the breast milk. We first showed that milk derived-MSCs were engrafted into the offspring organs when were taken orally. Milk derived-MSCs may elucidate the functional benefits to the newborn babies by increasing cell proliferation and growth. © 2016 IUBMB Life, 68(12):935-942, 2016.

THE EFFECT OF STEM CELLS AS AN ADJUVANT ON THE IMMUNOGENICITY OF A POTENTIAL ANTI-SCHISTOSOMAL VACCINE IN MICE.

Vaccination against schistosomes can be targeted towards the prevention of infection and/or to the reduction of parasite fecundity and pathology. However, as eggs are responsible mainly for schistosomiasis pathology, so crude soluble egg antigen (SEA) seems suitable to be used as a potential vaccine. Many studies have provided new insights establishing a role for mesenchymal stem cells (MSCs) in liver regeneration and improvement of schistosomiasis hepatic fibrosis, in addition to the need for standardized and effective adjuvant-vaccine formulations. So, the aim of this work is to evaluate the effect of stem cells when used as an adjuvant of a potential anti-schistosomal vaccine (crude SEA) in murine models. The current work was carried out on 100 mice (30 males for harvesting MSCs + 70 females for seven study groups, each of 10). A schedule of vaccination and challenge infection was followed so, GI (control healthy), G2 (control infected only) infected subcutaneously with S. mansoni cercaria (80-90 Schistosoma mansoni cercariae suspended in 0.2 ml distilled Water), G 3 (FCA then infected) received Freund's complete adjuvant (FCA) then infected, G4 (MSCs then infected) received MSCs then infected, G5 (SEA then infected) received SEA vaccine then infected, G6 (SEA+FCA then infected) received SEA vaccine and FCA then infected, G7 (SEA+MSCs then infected) received SEA vaccine and MSCs then infected. The current work was assessed by histopathological study and morphometric analysis (using H&E and Masson's Trichrome stains) to highlight number, size and type of liver granulomas and percentage of liver fibrosis, immunological and molecular studies (RNA extraction, Re- verse Transcriptase and PCR technique) for detection of interleukin-10 mRNA gene expression in liver tissue by reverse transcriptase & polymerase chain reaction (RT & PCR). The results showed that a- SEA alone as a potential anti-schistosomal vaccine was more or less moderately protective, b- MSCs alone before the infection had mild prophylactic effects, c- MSCs as an adjuvant of the crude SEA increased its capabilities with highly significant results regarding the decrease in granuloma number, size, percentage and density of hepatic fi- brosis, and d-There was significant increase in IL-10 mRNA gene expression on using (SEA+MSCs) (G7) if compared to other tested groups.

Influence of Matrix metalloproteinase 1 and 3 genetic variations on susceptibility and severity of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease affecting children aged less than 16 years, characterized by chronic synovitis, cartilage damage, and bony erosions mediated by matrix metalloproteinases (MMPs), mainly MMP-1 and MMP-3. The purpose of this study was to investigate MMP-1 and MMP-3 gene polymorphisms in patients with JIA, the role of genes in susceptibility to JIA, and their associations with JIA activity and prognosis. Case-control study included 100 patients diagnosed with JIA, according to the criteria of the International League of Associations for Rheumatology (ILAR), and 100 healthy children, age and sex matched, as controls. The MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of MMP-1 and MMP 3 were measured by enzyme-linked immunosorbent assay. There were significant differences between patients with JIA and control groups regarding the genotype and allele frequencies distributions of both MMP-1 1G/2G and MMP-3 5A/6A polymorphisms. The haplotype 2G-6A, which carries the abnormal alleles, showed higher frequencies in patients with JIA than in controls (OD = 2.8, P = 0.002). The prevalence of MMP-1 2G and 6A allele for MMP-3 polymorphism was found to be significantly associated with persistent oligoarticular, rheumatoid factor (RF)-positive polyarthritis, and systemic JIA groups. There were significantly increased serum levels of MMP-1 and MMP-3 associated with 2G/6A haplotype in the patient group, especially with the polyarticular RF (+ve) group than in other groups and the control group. MMP-1 and MMP-3 haplotypes could be useful genetic markers for JIA susceptibility and severity in the juvenile Egyptian population. Moreover, our data further support the use of serum MMP-3 and MMP-1 as specific markers of disease activity in JIA.

The role of placenta-derived mesenchymal stem cells in healing of induced full-thickness skin wound in a mouse model.

We examined the effect of placenta-derived MSCs (PDMSCs) injection intraregionally and intraperitoneally on healing of induced full thickness mice skin wounds; moreover, the mechanisms by which MSCs exert their effects were also studied. Sixty female mice were divided into three groups after induction of full thickness skin wound; untreated group, wounded mice were injected with MSCs derived from human placenta intraperitoneally or intraregionally. Skin biopsies were obtained 7 and 12 days after wound incision for histological examinations, detection of vascular endothelial growth factor (VEGF) by ELISA, and estimation of expression of mouse ICAM-1, Integrin ß1, Integrin ß3 genes and human albumin and GAPDH genes by reverse transcription polymerase chain reaction. Human placenta derived-MSCs treated groups showed accelerated wound healing than non-treated group. VEGF, Integrin ß1, and Integrin ß3 levels were significantly increased in the intraregionally and intraperitoneally treated mice as compared to non-treated group at day 7 after wound induction. ICAM-1 showed significant decrease in its expression in treated groups compared with non-treated group. Interestingly, the intraperitoneal MSCs injections showed better results than intraregional one. PDMSCs accelerate full thickness skin wound healing and the intraperitoneal MSCs injections are more effective than intraregional one. MSCs promote wound healing through release of proangiogenic factors as VEGF, increase healing promoting factors as integrin ß1 and ß3, and decrease proinflammatory cytokines as ICAM-1.

Human peripheral blood CD34+ cells attenuate oleic acid-induced acute lung injury in rats.

BACKGROUND AIMS: Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury (ALI). In this study, we evaluated the therapeutic effect of isolated human peripheral blood CD34+ progenitor cells in an ALI rat model, induced by oleic acid (OA) injection. METHODS: Seventy-five adult female rats were used in this study. Group A, control without treatment, and group B, control injected with phosphate-buffered saline, comprised 15 rats each; the remaining 45 rats were injected with OA to induce ALI and were further subdivided into 3 groups: group C (ALI group, 15 rats), group D (ALI and fibroblast group, 15 rats) and group E (ALI and CD34+ cell group, 15 rats). RESULTS: CD34+ cells transplantation in rats with OA-induced lung injury improves the arterial PaO(2) and wet/dry ratio, reduces infiltration of inflammatory cells and decreases lung vascular permeability as determined by reduced intra-alveolar and interstitial patchy congestion and hemorrhage as well as decreased interstitial edema. Additionally, lung inflammation determined by expression of the pro-inflammatory mediators intercellular adhesion molecule 1 and tumor necrosis factor-α was attenuated in CD34+ cell-treated rats at 6, 24 and 48 h post-OA challenge compared with non-treated rats. Moreover, the expression of anti-inflammatory molecule interleukin-10 was up-regulated in the lung of OA-induced ALI rats after administration of CD34+ cells. The important finding was that human TNF-α-induced protein 6 (TSG-6) gene expression was significantly up-regulated in rats treated with CD34+ cells. CONCLUSIONS: The freshly isolated human peripheral blood-derived CD34+ cells may be used as an important source of stem cells that improve ALI. The anti-inflammatory properties of CD34+ cells in the lung are explained, at least in part, by activation of CD34+ cells to express TSG-6.

Effect of bone marrow-derived mesenchymal stromal cells on hepatoma.

BACKGROUND AIMS: The aim of the study was to evaluate the effect of mesenchymal stromal cells (MSCs) on tumor cell growth in vitro and in vivo and to elucidate the apoptotic and anti-proliferative mechanisms of MSCs on a hepatocellular carcinoma (HCC) murine model. METHODS: The growth-inhibitory effect of MSCs on the Hepa 1-6 cell line was tested by means of methyl thiazolyl diphenyl-tetrazolium assay. Eighty female mice were randomized into four groups: group 1 consisted of 20 mice that received MSCs only by intrahepatic injection; group 2 consisted of 20 HCC mice induced by inoculation of Hepa 1-6 cells into livers without MSC treatment; group 3 consisted of 20 mice that received MSCs after induction of liver cancer; group 4 consisted of 20 mice that received MSCs after induction of liver cancer on top of induced biliary cirrhosis. RESULTS: MSCs exhibited a growth-inhibitory effect on Hepa 1-6 murine cell line in vitro. Concerning in vivo study, decreases of serum alanine transaminase, aspartate transaminase and albumin levels after MSC transplantation in groups 2 and 3 were found. Gene expression of α-fetoprotein was significantly downregulated after MSC injection in the HCC groups. We found that gene expression of caspase 3, P21 and P53 was significantly upregulated, whereas gene expression of Bcl-2 and survivin was downregulated in the HCC groups after MSC injection. Liver specimens of the HCC groups confirmed the presence of dysplasia. The histopathological picture was improved after administration of MSCs to groups 2 and 3. CONCLUSIONS: MSCs upregulated genes that help apoptosis and downregulated genes that reduce apoptosis. Therefore, MSCs could inhibit cell division of HCC and potentiate their death.

Mesenchymal stromal cell injection protects against oxidative stress in Escherichia coli-induced acute lung injury in mice.

BACKGROUND AIMS: Stem cells may be a promising therapy for acute respiratory distress syndrome. Recent in vivo and in vitro studies suggested that the mesenchymal stromal cells (MSCs) have anti-oxidative stress properties. We hypothesized that intravenous injection of bone marrow-derived mesenchymal stem cells (MSCs) could attenuate Escherichia coli-induced acute lung injury (ALI) in mice by controlling the oxidative stress status. METHODS: Eighty mice were randomly divided into four groups: group 1 (control group) received 25 µL of saline as a vehicle; group 2 contained E coli-induced ALI mice; group 3 included mice that received MSCs before induction of ALI; group 4 included mice that received MSCs after induction of ALI. Lung samples were isolated and assayed for oxidative stress variables and histopathologic analysis. Total anti-oxidant capacity was measured in broncho-alveolar lavage. RESULTS: Pre- and post-injury MSC injection increased survival, reduced pulmonary edema and attenuated lung injuries in ALI mice. Histologically, MSCs exhibited a considerable degree of preservation of the pulmonary alveolar architecture. An increase of anti-oxidant enzyme activities and a decrease of myeloperoxidase activity and malondialdehyde levels in the MSC recipient groups versus the ALI group were found. Furthermore, the total anti-oxidant capacity and reduced glutathione levels were significantly increased in MSCs recipient groups versus the ALI group. Weak +ve inducible nitric oxide synthase immuno-expression in groups that received MSCs was detected. Pre-injury MSC injection showed better effects than did post-injury MSC injection. CONCLUSIONS: Systemic bone marrow-derived MSC injection was effective in modulating the oxidative stress status in E coli-induced acute lung injury in mice.

Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. The aim of this study was to investigate the association between vitamin D status and VDR gene polymorphisms and T1DM. MATERIALS AND METHODS: One hundred and twenty patients with T1DM and one hundred and twenty controls were enrolled in the study. VDR gene BsmI, FokI, ApaI and TaqI polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum 25-hydroxyvitamin D (25(OH)D) was determined using ELISA. RESULT: Serum 25(OH)D levels revealed a vitamin D deficiency or insufficiency in 75% of the patients. The mean levels of vitamin D were significantly lower in patients as compared to their controls (P=<0.001). VDR BsmI Bb and bb genotypes and VDR FokI Ff and ff genotypes were associated with increased risk of T1DM (OR=2.3, 95% CI=1.3-4.2, P=0.005; OR=2.2, 95% CI=1.1-4.7, P=0.04; OR=1.8, 95% CI=1.03-3.04, P=0.04; OR=4.03, 95% CI=1.2-13.1, P=0.01 respectively), while the VDR ApaI and TaqI polymorphisms were not. CONCLUSION: Our study indicated that vitamin D deficiency and VDR BsmI and FokI polymorphisms were associated with T1DM in Egyptian children.

Mechanistic action of mesenchymal stem cell injection in the treatment of chemically induced ovarian failure in rabbits.

BACKGROUND: No curative treatment is known for primary ovarian failure; however, mesenchymal stem cells (MSCs), through self-renewal and regeneration, push the trial to evaluate their role in the treatment of ovarian failure. The aim of this study was to explore the impact of MSCs on cyclophosphamide (CTX)-induced ovarian failure in rabbits and to clarify the mechanism(s) by which MSCs exert their action. METHODS: Thirty-five adult female rabbits were injected with CTX to induce ovarian failure. Five rabbits were euthanized after the last injection of CTX for histological examination. The others (30 rabbits) were further subdivided into two groups: group 1 (ovarian failure group, 15 rabbits) received no treatment; group 2 (ovarian failure and MSC recipient group, 15 rabbits) received MSCs isolated from extracted bone marrow of male rabbits. RESULTS: A decrease of follicle-stimulating hormone and an increase of estrogen and vascular endothelial growth factor (VEGF) levels in the MSC recipient group versus the ovarian failure group were found. Weak caspase-3 expression and +ve proliferating cell nuclear antigen staining after MSC injection were detected. Cytological and histological examinations showed increased follicle numbers with apparent normal structure of ovarian follicles in the MSC recipient group. Moreover, Y chromosome-containing cells from male donors were present within the ovarian tissues in group 2. CONCLUSIONS: The current study suggests that intravenous injection of MSCs into rabbits with chemotherapy-induced ovarian damage improved ovarian function. MSCs accomplish this function by direct differentiation into specific cellular phenotypes and by secretion of VEGF, which influence the regeneration of the ovary.

PADI4 polymorphisms and related haplotype in rheumatoid arthritis patients.

OBJECTIVE: To investigate whether peptidyl arginine deiminase type IV gene (PADI4) polymorphisms contribute to rheumatoid arthritis (RA) susceptibility in Egyptians, whether they influence disease severity and activity, and whether they affect anti-mutated citrullinated vimentin antibodies (anti-MCV) level. METHODS: Three PADI4 single nucleotide polymorphisms (SNPs) (PADI4-92, PADI4-96, and PADI4-102) were screened in 275 RA patients and 275 unaffected controls by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. Serum anti-MCV levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were significant associations between RA susceptibility with the minor alleles of PADI4-92 and PADI4-102 [odds ratio (OD) and 95% confidence interval (CI) for the minor alleles of PADI4-92 and PADI4-102: 1.48 (1.17-1.88) and 2.05 (1.61-2.61) respectively] but not with PADI4-96 [OD and 95% CI for the C allele: 1.09 (0.86-1.39)]. PADI4 haplotypes 2 (GCC) and 3 (GCT) were also associated with RA susceptibility while PADI4 haplotypes 1 (CTC) may be protective against developing of this disease. A significant association was detected between PADI4 haplotypes and RA severity. CONCLUSIONS: The PADI4 SNPs and haplotypes were associated with RA susceptibility, although no relation was observed between the PADI4 haplotypes and anti-MCV levels.

Variation of matrix metalloproteinase 1 and 3 haplotypes and their serum levels in patients with rheumatoid arthritis and osteoarthritis.

The matrix metalloproteinases 1 and 3 (MMP1 and MMP3) are thought to be important in destructive joint changes seen in rheumatoid arthritis (RA) and osteoarthritis (OA) diseases. The aim of this study was to analyze whether functional polymorphisms in the promoter region of the MMP1 and MMP3 genes were associated with RA and OA. The MMP1 (-1607 1G/2G) and MMP3 (-1171 5A/6A) polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism in 100 patients with (RA), 100 patients with (OA), and 100 controls. Serum MMP1 and MMP3 levels were measured by enzyme-linked immunosorbent assay. The results reported a significant difference between patients with OA and controls regarding allele distributions of MMP1 polymorphism, but not between patients with RA and controls. For MMP3 polymorphism, the 6A/6A genotype was significantly more frequent in patients with RA and OA than in controls. The haplotype 2G-6A, which carries the abnormal alleles, showed higher frequencies in the patients with RA and OA than in controls (28%, 30% and 8%, respectively). There were no significant differences in serum MMP1 and MMP3 levels between all studied groups. In conclusion, the MMP1 and MMP3 haplotypes may represent genetic determinants for RA and OA in the Egyptian population. The results suggest that MMP polymorphism genotypes may be more useful in predicting joint damage than measurement of serum concentrations of MMP1 and MMP3. Moreover, MMP1 and MMP3 polymorphisms may predict the activity and severity of these diseases.

Insulin-like growth factor binding protein-1 and glycodelin levels in uterine flushing before and after hysteroscopic polypectomy.

BACKGROUND: Endometrial polyps are one of the most common endometrial abnormalities and it may be associated with infertility and early pregnancy loss. The aim of this study was to investigate the levels of insulin-like growth factor 1 binding protein (IGFBP-1) and glycodelin levels in uterine flushings before and after hysteroscopic polypectomy. METHODS: Two-hundred fifty non pregnant women participated in this prospective interventional study. One-hundred women with a complaint of infertility had endometrial polyps diagnosed by two-dimensional ultrasound scan and confirmed by transvaginal sonohysterography were prepared for hysteroscopic polypectomy, and 150 women with a history of menorrhagia not responding to medical treatment were prepared for hysteroscopic endometrial biopsy. Paired samples of uterine flushings were taken from all patients prior to and post hysteroscopic intervenetion at the midluteal phase. Insulin-like growth factor binding protein-1 was analyzed using an immunoradiometric assay. Enzyme-linked immunoassays were performed to analyze glycodelin. Glycodelin and IGFBP-1 levels were compared in both groups prior to and post hysteroscopic intervention. RESULTS: The glycodelin and IGFBP-1 levels are significantly lower in patients with uterine polyps than in patients having menorrhagia preoperatively (p < 0.001 for each). In patients with uterine polyps, both glycodelin and IGFBP-1 were significantly increased postoperatively (p < 0.001 for each), while no significant changes in their values were noted postoperatively in patients with menorrhagia undergoing endometrial biopsy. CONCLUSIONS: Decreased levels of mid-secretory IGFBP-1 and glycodelin were associated with the presence of endometrial polyps and both were reversed following hysteroscopic polypectomy. This could explain the pathophysiological mechanisms by which endometrial receptivity is impaired in the presence of endometrial polyps.