مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و دوم شماره 6 (پیاپی 162، شهریور 1393)

Mesenchymal Stem Cells (MSCs) are well known as the regulator of the immune system. These multipotent non-hematopoietic progenitor cells have been originally isolated from bone marrow, and later on found in several other tissues, such as skeletal muscle, umbilical cord blood, adipose and fetal liver tissues. Immunomodulatory effects of MSCs on a variety of immune cells such as T and B lymphocytes, Natural Killer cells (NK), neutrophils, macrophages and dendritic cells, has made a good candidate of them for the treatment of inflammatory disorders, particularly autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. In addition, several studies have indicated mechanisms by which MSCs could reduce immune cell proliferation and activation leading to immune tolerance induction. Since T lymphocytes are considered as the most important immune cells, effect of MSCs on the activity of these cells has a very special significance to direct immune response. Under various conditions, T-lymphocytes have different phenotype and performance and can be differentiated into particular subtype such as regulatory T cells. Both in vitro and in vivo studies have indicated that MSCs modulate innate and adaptive immune system by promoting generation of CD4+CD25+ T regulatory cells which have important role in immune tolerance induction and autoimmune disease prevention. MSCs are able to block pro-inflammatory and increase anti-inflammatory cytokines secretion. So such unique immunomodulatory features make MSCs ideal candidates for clinical application as immunosuppressants which can be considered for autoimmune diseases treatment. Therefore, in this short-review, we attempt to focus mainly on the existing information about MSCs in association with immunomodulatory function of them on the immune system. In addition, the possible mechanisms and the performance impact of MSCs in autoimmune diseases improvement are discussed here. However, increasing knowledge of how MSCs will influence on the immune system suppression, leading us to better use of these cells as a promising tool in the treatment of autoimmune diseases.

With the aim of regenerating healthy tissues, different tissue engineering strategies pointed to extracellular matrix (ECM)-based scaffolds in tissue engineering and regenerative medicine and wound healing. It is a multidisciplinary science works to create biocompatible scaffolds with perfect physical parameters, mechanical integrity and high porosity to promote cell growth, migration and angiogenesis. With the increased incidence of obesity, subcutaneous adipose tissue is abundant and readily accessible. Liposuction surgeries yield from 100 mL to 3 L of lipoaspirate tissue. We present our prepared acellular ECM powders derived from human adipose tissue obtained from lipoaspirate, which contains large amounts of collagen suitable for induction of adipogenesis. The study had been carried out from December 2012 to March 2013 in Tissue Bank and Research Center in Imam Khomeini Hospital Tehran, Iran. Fresh human adipose tissue was obtained by liposuction of abdominal fat pad in a private Day Clinic. By using wasted material of liposuction, we obtained 100 to 200 cc fat tissue from each patient. After physical (freeze-thaw-slicing-manual massage) and chemical (enzymatic-detergent-acid digestion) treatment, an acellularized matrix was created from fat tissue. The final material lyophilized and ground to powder. We analyzed ultra structure and biochemical properties of obtained ECM powder by using electron microscopy, immunohistochemistry (IHC) examination and proteomic studies. After mechanical and chemical process of decellularization, scanning electron micrographs of the samples showed smooth and contiguous collagenous components throughout the scaffold. IHC showed strong positive labeling for collagen IV and no evidence of nuclear material in the specimen. Separation of protein complex by Blue Native Polyacrylamide gel electrophoresis (BN-PAGE) has proven type I collagen triple helices associate to form banded fibrils. RNA preparation and Gene Expression Analysis (RT-PCR) by using specific primers for laminin, fibronectin, collagen type I and IV, desmin, and actin showed strong staining of our fat tissue scaffold with collagen type I, fibronectin, collagen IV and laminin. The results show that our decellularization method produced an adipose ECM scaffold rich of collagen fibers, suitable and effective substrate for use in soft tissue engineering and regenerative medicine.

Leptin is an adipokine made by fat cells and plays a key role in proliferation, cell survival, migration and immune response. Several studies have suggested that individuals with high serum leptin concentrations would increase the risk of breast cancer. G -2548A polymorphism in the leptin gene is located in the promoter region and is associated with the change of leptin serum level. In this study, the association between G -2548A polymorphism in leptin gene and breast cancer susceptibility was investigated. This case-control study was done on 374 Iranian women. This study was performed from March 2013 to February 2013. Blood samples from 203 women with breast cancer and 171 age (±5)- matched healthy women were collected. Breast cancer patients were selected from Namazi Hospital in Shiraz city. Genomic DNA was extracted from blood samples. The G -2548A polymorphism of leptin gene was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was performed by SPSS version 18. Logistic regression analysis was used for association of breast cancer susceptibility and G -2548A polymorphism of leptin gene. The A allele frequency was 60% in control group and 72% in breast cancer patients. There was a significant association between A allele in -2548 position of leptin gene and breast cancer susceptibility (OR: 1.8, 95% CI: 1.3-2.4, P<0.001). In the reces-sive effect of the A allele (comparison between AA vs. AG+GG), AA genotype in -2548 region of leptin promoter sequence was significantly increased the risk of breast cancer (OR=2.2, 95% CI: 1.5-3.4, P<0.001). It is concluded that A allele in the -2548 promoter region of leptin gene may act as a recessive allele and increase the breast cancer risk.

Stem cells are applied in the treatment of wide range of diseases and can be separated from different tissues of the body. These cells can treat diseases by cytokine and growth factor secretion and also cell differentiation. Burn wound is a challenging problem of reconstructive surgery and stem cells may help wound healing process. We designed this study to evaluate the beneficial effect of fat derived stem cells for coverage of 3rd degree burn wound. This study was experimental and has been done in Burn Research Center of Iran University of Medical Sciences during January 2012 to April 2013. Thirty rats randomly divided to three equal groups. Inguinal fat of 10 rats (one group) were used for preparation of autologous adipose-derived mesenchymal stem cells. Acellular amnion was used as a scaffold for stem cell transfer. Each of the thirty rats had been exposed to a cm deep 3rd degree burn on back area. 24 hours after surgery, the wound was excised and it had been covered by three conventional dressing in the first group, acellular amnion in the second group and acellular amnion seeded with adipose-derived stem cell in the third group. The rate of wound healing and pathologic characteristics was compared in all three groups. Healing rate and decrease in wounds size was significantly better in acellular amnion seeded with adipose-derived stem cells compared with other two groups at 3rd and 15th days after surgery P<0.01. Also in histopathology examination, fibroplasia and neovascularization of wounds were significantly better in stem cells group than the other two groups P<0.001. Acellular amnion seeded with adipose-derived stem cell can result in faster wound healing and better histopathology characteristic. The amnion as a scaffold and the fat derived stem cells as healing accelerator are recommended for coverage of the 3rd degree burn wounds after excision and it may reduce the need for skin graft.

The occlusion of the artery and vein grafts are currently a major problem in coronary bypass surgery. Degradation of collagen and elastin, the most abundant extracellular matrix proteins in the vessel wall by matrix metalloproteinase (MMPs), leads to a rearrangement of the extracellular matrix and vascular wall structure. The present study aimed to compare the histological and biochemical characteristics of arteries and veins which could have a role in the failure of the graft.

This study was a cross-sectional study of 80 patients conducted at Heart Hospitals in Isfahan, Iran, between July 2012 and November 2013. Samples were collected from the remains of vessels used in bypass surgery of 11 male nondiabetic patients. The histologic, collagen elastin ratio and MMPs levels of the vessels were investigated. MMPs were determined using the Gelatin Zymography method. For elastin and collagen content measurement, the sample was digested by cyanogen bromide and hydrochloric acid and then hydroxyproline was measured with a spectrophotometer.

The amount of active and inactive MMP-2 and MMP-9 of the left internal mammary artery (Lima) was similar to aorta, but the amount of MMP-2 and MMP-9 in the radial artery and saphenous vein were significantly higher than aorta. Elastin to collagen ratio in Lima (1.92±1.15) was similar to the aorta (3.4±1.66), but this proportion in saphenous vein (1.07±0.47) and radial artery (1.14±0.39) was significantly lower in the aorta (P≤0.05). Most patients had atherosclerotic plaque in radial while there was atherosclerotic plaque in Lima of only one case.

The presence of atherosclerotic plaques in radial and thickening of the intimal layer of the saphenous vein in the majority of patients and decrease of collagen to elastin ratio and the high level of matrix metalloproteinase enzymes in the radial and saphenous vein can induce early pathological conditions, and remodeling of the vessels involved. So the results of this study confirm that Left Internal Mammary Artery (LIMA) is the most suitable candidate for bypass surgery.

Gonadotropins are commonly used for superovulation in human and animals to retrieve more oocyte and increase chance of pregnancy. Ovarian stimulation in assisted reproduction technology produces lower implantation rates per embryo transferred than natural and ovum donation cycles, suggesting suboptimal endometrial development due to the hormones used to recruit more oocytes. Due to the frequent use of gonadotropins in the treatment of infertility in successive periods, the aim of this study was to determine the endometrial changes in response to repeated ovarian stimulation. This experimental interventional study has done in research center of Hamadan university of medical sciences in 2012. NMRI female mice six weeks old were used in this study and divided into 7 groups (5 each). The mice in group 1, 2, 3 and 4 received 1, 2, 3 and 4 times pregnant mare serum gonadotropin (PMSG) and 48 hours later 7.5 IU human chorionic gonadotrophin (hCG) respectively. For each group were considered a control group which received on time gonadortropin injection. The mouses were killed 13-16 hours after hCG injection and middle part of uterine horn cut for histological study using Hematoxylin and Eosin staining. The parameters that studied were surface epithelium of endometrium, glandular epithelium, and endometrial height and axis of uterine gland. Our results showed that there are no significant differences in glandular epithelium, axis of glands and height of endometrium in experimental groups (P>0.05). The height of surface epithelium showed significant increases after ovarian stimulation in experiment group (P≤0.03). Our results showed that there are no significant differences in glandular epithelium, axis of glands, height of endometrium and height of surface epithelium between control groups and also it's experimental group (P>0.05). Changes in the height of surface epithelium could be one of the reasons for decrease implantation rates with repeated ovarian stimulation.

Lack of precise diagnostic criteria and sufficient findings in support of biopsy sampling during upper gastrointestinal endoscopy is one of the special challenge in endoscopy assessment in Barrett's esophagus. The aim of this study was to evaluate the mucosa in the distal esophagus tissues through a biopsy during upper gastrointestinal endoscopy in gastroesophogeal reflux disease patients whose symptoms dont improve or only partially resolve with treatment. A cross-sectional study was done in patients with gastroesophogeal reflux disease medically resistant to treatment. The patients were assessed by gastroenterology department in Sina Hospital, Tehran, Iran, since September 2012 to September 2013. Patients with coagulopathy, esophageal varicose, esophageal cancer, earlier detection of developing Barrett's esophagus, history of irritable bowel syndrome, psychological disorders and using of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, were excluded. Esophageal squamous epithelium and cylindrical tissue of stomach was carefully checked by endoscope. Then 2 to 4 biopsy of the Z-line above the gastroesophageal mucosa were obtained. One hundred and fifty three patients included 78 men (51%) and 75 females (49%) with a mean age of 47.92±17.57 years participated in the study. The mean of body mass index of patients was 25.05±4.17 kg/m2 and body mass index in 45.8 % of the patients more than 230 kg/m2. Biopsy specimens were taken in 31 cases were not enough for histological examination. In other patients, 25 cases (20.5%) were normal and 97 cases (79.5%) had the following pathological diagnosis: mild esophagitis (49 cases; 40.2%), moderate esophagitis (24 cases; 19.7%), severe esophagitis (14 cases; 11.5%), Barrett's esophagus (8 cases, 6.5%), fungal esophagitis (1 cases, 0.8%), and eosinophilic esophagitis (1 cases; 0.8%). 117 patients (76.5%) had H. pylori infection. Sensitivity and specifity of endoscopy for detection of Barrett's esophagus during upper gastrointestinal endoscopy were 100% and 84.13% (CI 95%:78.53-89.09%), respectively. Our data showed that doing of accurate and adequate biopsy samples from lesions in upper GI endoscopy can be helpful in the diagnosis of Barrett's esophagus

Several risk factors like prematurity, hyperoxia, hyperglycemia, duration of mechanical ventilation and supplemental oxygen use have been attributed to the occurrence of retinopathy of prematurity (ROP) in low birth weight infants. Clinical Risk Index for Babies (CRIB) score have been used to assess the severity of the newborn's disease and neonatal mortality. The relation between the CRIB score and the incidence of retinopathy of prematurity is less assessed. This study was carried out to determine the relation between the CRIB score and retinopathy of prematurity in preterm infants. In a cross-sectional study all preterm infants admitted to NICU from March 2009 to November 2012, with a birth weight less than 1500 grams and gestational age less than 28 weeks and other premature infants with birth weight 1500 to 2000 grams and gestational age 29 to 34 weeks with an unstable clinical condition, were included. The CRIB score was recorded in firs 12 hours of admission to the NICU. Ophthalmologic examination was done by a retinologist unaware of CRIB score. ROP classification was done according to the international classification of ROP. The CRIB score compared with presence or non-presence of ROP and its stage, progression or regression of disease. A P-value less than 0.05 are considered significant. One hundred and eighty (70%) neonates out of 256 neonates developed ROP. In 124 (68.88%) neonates it resolved spontaneously on serial ophthalmologic examination, but fifty-six (31.11%) neonates were required treatment for ROP which 42 (75%) received Avastin and 14 (25%) neonates treated with Laser. The Mean±SD for CRIB score in ROP group was 4.79±2.74 and in a group without ROP it was 3.78±2.00 (P=0.004). No correlation was found between the severity of ROP and CRIB score (P=0.152). The CRIB score can predict the occurrence of ROP, but cant predict its severity and progression or regression.

Insulin resistant is important risk factors of diabetes and leads to development of chronic diseases such as diabetes and cardiovascular disease. Recent studies showed association between androgenic alopecia and insulin resistant. However, findings are controversial. Alopecia in women is a common heritable hair loss in central part of head. Aim of this study was investigation of androgenic alopecia distribution in type II diabetes and healthy women and hypothesis testing of relationship between diabetes and androgenic alopecia. This is a case-control study. Case and control groups were selected from type II diabetes and healthy women respectively that were refered to clinics of Alzahra, Noor and Amin Hospitals in Isfahan City, Iran in 2011. Participants were selected based on random sampling. Sample size was estimated 141 subjects in each group. Participants were visited by doctor and severity of androgenic alopecia was determined based on Ludwish criteria. Data were analyzed with SPSS software and 2 test. P<0.05 was considered as significant. Mean age and body mass index were 58.96±12.8 year and 25.6±4.15 kg/m2 respectively in whole population. Findings not show any significant association between type II diabetes and androgenic alopecia (P<0.05). Comparison of distribution of alopecia severity according to Ludwish criteria separately showed similar result. In addition to, there was not any significant relationship between diabetes and alopecia after adjusting with body mass index as confounding factor (P<0.05). In the present study, there was not any significant relationship between type II diabetes and androgenic alopecia among diabetes and healthy women. However, more researches need to investigate this relationship in both gender and assess insulin resistant indices as homeostasis model assessment-estimated insulin resistance and androgenic alopecia.

Distribution of Tuberculosis (TB) has a special template affected by geographic and social factors. Nowadays Geographical Information System (GIS) software is one of the most important and useful epidemiologic devise for identifying geographic areas and high risk population for infection by TB. Aim of this study was assessment of Tuberculosis distribution by GIS in Khuzestan province, Iran. In this retrospective cohort study, documents of 6363 TB patients identified in Khuzestan province at the beginning of 2005 until the end of the September of 2012 were assessed and sampling method was census. The data was gathered by TB-Register Center. TB incidence was evaluated by GIS maps according to climatic and vegetation with 1:25,000 scale. The data was analyzed in SPSS software and means plot and Independent’s t-test, ANOVA with a significance level of less than 5% and Eta Correlation. Spread of Tuberculosis in climatic and vegetation were plotted in GIS maps, cumulative incidence rate was calculated separately for each area. There was a statistical significant relationship between cumulative incidence rate of disease and climatic (P=0.017) and the Eta correlation coefficient was 0.379 (P=0.011). There was a statistical significant relationship between cumulative incidence rate of TB and vegetation (P=0.004) and the Eta correlation coefficient was 0.388 (P=0.188). Mean age and median age of patients were 39.3±18 and 35±6.5 years respectively. For women, mean age was 2.1 years older than men and this difference was statistically significant. (P=0.0001). The risk of TB infection is closely associated with the climatic and vegetation. So the risk of TB in extra-dry climate and vegetation of highland meadows is more than other areas. Special care and services to high-risk areas is recommended.