BACKGROUND AND OBJECTIVES: Genomic imprinting is an inheritance phenomenon by which a subset of genes are expressed from one allele of two homologous chromosomes in a parent of origin-specific manner. Even though fine-tuned regulation of genomic imprinting process is essential for normal development, no other means are available to study genomic imprinting in human during embryonic development. In relation with this bottleneck, differentiation of human embryonic stem cells (hESCs) into specialized lineages may be considered as an alternative to mimic human development. METHODS AND RESULTS: In this study, hESCs were differentiated into three lineage cell types to analyze temporal and spatial expression of imprinted genes. Of 19 imprinted genes examined, 15 imprinted genes showed similar transcriptional level among two hESC lines and two human induced pluripotent stem cell (hiPSC) lines. Expressional patterns of most imprinted genes were varied in progenitors and fully differentiated cells which were derived from hESCs. Also, no consistence was observed in the expression pattern of imprinted genes within an imprinting domain during in vitro differentiation of hESCs into three lineage cell types. CONCLUSIONS: Transcriptional expression of imprinted genes is regulated in a cell type-specific manner in hESCs during in vitro differentiation.
Alleles ; Embryonic Development ; Embryonic Stem Cells* ; Female ; Genomic Imprinting ; Human Development ; Humans ; Parents ; Pluripotent Stem Cells ; Pregnancy ; Wills

BACKGROUND AND OBJECTIVES: Placenta and blood that remained in the umbilical cord is routinely available as a discarded tissue after deliveries and it is free of any legal, moral, ethical or religious objections, providing a high number of multipotent CD34+ progenitor and stem cells. Using ex vivo isolated CD34+ cells from human umbilical cord blood (hUCB) have emerged as promising candidates to treat various diseases, including exogenous pathogenic infections. We have expanded to build a rational approach to study the effect of CD34+ cells after damaged liver tissues by the devastating human parasitic flatworm Schistosoma mansoni. METHODS AND RESULTS: Experimental studies were conducted in the Department of Zoology, Faculty of Science and Departments of Parasitology and Physiology, Faculty of Medicine, SCU, Egypt. We have studied the impact of ex vivo preparation of CD34+ cells from hUCB on S. mansoni-induced liver fibrosis de novo, and treated for shorter and longer periods in vivo. Ova count, ALT and albumin were measured at specific time interval and histopathological examination of liver was conducted to confirm the biochemical results. The data obtained were statistically analyzed by ANOVA between groups. It was found that the administration of CD34+ cells have modestly reduced liver damage; reduced the S. mansoni infection associated elevation in serum levels of ALT; significantly improved serum levels of albumin and reduced egg granuloma diameter in the livers. CONCLUSIONS: We demonstrated that CD34+ cells can markedly ameliorated liver fibrosis in vivo and may be beneficial for therapy to recover organ structure and/or function of S. mansoni-infected mice.
Animals ; Egypt ; Fetal Blood ; Fibrosis ; Granuloma ; Humans ; Liver ; Liver Cirrhosis ; Mice* ; Ovum ; Parasitology ; Physiology ; Placenta ; Platyhelminths ; Schistosoma mansoni* ; Stem Cells ; Umbilical Cord ; Zoology

BACKGROUND AND OBJECTIVES: Variety of pathological factors including viral hepatitis, alcohol and drug abuse, metabolic diseases, autoimmune diseases and congenital abnormalities can cause hepatic injury. Liver transplantation is the treatment of choice for end-stage liver diseases, however, it faces several difficulties. So the aim of the work is to evaluate the effect of bone marrow derived mesenchymal stem cells (BM-MSCs) on the liver structure in carbon tetra chloride CCL4 induced liver fibrosis in rats. MATERIALS AND RESULTS: BM-MSCs were isolated and characterized from long bones of twenty male albino rats. Sixty female rats were divided into the following two groups: Group I; thirty rats which were the control group. Group II; thirty rats were injected intra-peritoneal (IP) by CCL4 twice weekly for four weeks and was further subdivided into the following three subgroups: Subgroup IIA (CCL4 alone); included ten rats which were sacrificed after this four weeks. Subgroup IIB (CCL4/MSCs); included ten rats which were IP injected by a single dose of BM-MSCs and were sacrificed after four weeks. Subgroup IIC (CCL4/recovery); included ten rats which were left for another four weeks without any intervention. Histological examination of liver specimens showed that CCl4 caused variable pathological changes with elevated liver enzymes. Injection of BM-MSCs revealed an improvement in the histological picture of the liver and its enzymatic profile. On the other hand, most of the pathological lesion were still detected in rats of recovery group. CONCLUSIONS: BM-MSC could restore the liver structure and function in experimental model of liver fibrosis.
Animals ; Autoimmune Diseases ; Bone Marrow* ; Carbon ; Characidae ; Congenital Abnormalities ; Female ; Fibrosis ; Hand ; Hepatitis ; Humans ; Liver ; Liver Cirrhosis* ; Liver Diseases ; Liver Transplantation ; Male ; Mesenchymal Stromal Cells* ; Metabolic Diseases ; Models, Theoretical ; Rats* ; Substance-Related Disorders

BACKGROUND: Severe injuries in skeletal muscle result in muscle weakness that delays recovery and contribute to progressive decline in muscle function. Microcurrent therapy (MCT) is a novel treatment method used in soft tissue injury and tissue regeneration therapy. The regenerative capacity of skeletal muscle tissue resides in satellite cells, the quiescent adult stem cells. AIM: The present work aimed at investigating the relation between microcurrent therapy and local stem cells in regeneration of induced skeletal muscle injury in albino rat. MATERIALS AND METHODS: Twenty six adult male albino rats were divided into Sham group, Injury group (I): subjected to soleus muscle injury and subdivided into subgroups I1 & I2 sacrificed 2 and 4 weeks after injury respectively. Microcurrent group (M): subjected to muscle injury and micro-current was applied. The animals were subdivided into subgroups M1 and M2 sacrificed 2 and 4 weeks after injury. Histological, immunohistochemical and morphometric studies were performed. RESULTS: Atypical fibers widely separated by infiltrating cells and strong acidophilic sarcoplasm with focal vacuolations were found in injury group. In M1 subgroup few atypical fibers were found. In M2 subgroup multiple typical fibers were detected. A significant decrease in the mean area of atypical fibers, a significant increase in the mean area% of alpha SMA+ve cells and that of CD34+ve cells were found in microcurrent group compared to injury group. CONCLUSIONS: A definite therapeutic effect of the microcurrent was found on induced skeletal muscle injury. This effect was proved to be related to satellite cell activation.
Adult ; Adult Stem Cells ; Animals ; Humans ; Male ; Muscle Weakness ; Muscle, Skeletal* ; Nerve Fibers, Myelinated ; Rats ; Regeneration ; Soft Tissue Injuries ; Stem Cells*

BACKGROUND AND OBJECTIVES: Depression is one of the most prevalent psychiatric disorders. Endogenous neural stem cells (NSCs) could replace damaged Hippocampal neurons in depression. This work was planned to evaluate Rhodiola rosea (Rr) extract possible role in stimulation of NSCs proliferation and in depression improvement. METHODS AND RESULTS: Thirty adult male albino rats were divided into three groups; control, untreated depressed model and Rr model. After depression induction by chronic mild stress, rats received Rr extract 1.5 g/kg/day for three weeks. The sucrose preference test (SP) was done before, after depression induction and 3 weeks after supplementation of Rr. The brain was removed and processed for H&E and immunohistochemical staining for caspase 3, glial fibrillary acid protein (GFAP) and proliferating cell nuclear antigen (PCNA). Rr group revealed improved sucrose preference, increased undamaged neurons and decreased dark neurons. Moreover, Caspase 3 +ve cells were not detected, GFAP +ve cells increased and PCNA +ve cells were detected only in Rr group. CONCLUSIONS: This work points to the role of Rr in depression improvement and in stimulation of NSCs proliferation.
Adult ; Animals ; Brain ; Caspase 3 ; Depression* ; Glial Fibrillary Acidic Protein ; Humans ; Male ; Neural Stem Cells* ; Neurons ; Proliferating Cell Nuclear Antigen ; Rats* ; Rhodiola ; Sucrose

BACKGROUND AND OBJECTIVES: Stem cell-based therapy is a potential new approach in the treatment of stroke. However, the efficacy and safety of these treatments are not yet fully understood. Therefore, we performed a meta-analysis of available single-arm studies using stem cell-based therapy in patients with stroke. METHODS: We searched MEDLINE, EMBASE, and the Cochrane database for studies of stem cell therapy in patients with stroke from its inception through July 2014. The articles included in the search were restricted to the English language, studies with at least 5 patients, and those using cell-based therapies for treating stroke. RESULTS: Fourteen studies included in the meta-analysis. The pooled mean difference in National Institutes of Health Stroke Scale (NIHSS) scores from baseline to follow-up points was 5.7 points (95%CI: -8.2 to -3.2, I2=91.5%) decreased. Also the pooled mean difference in modified Bathel index (BI) score was increased by 31.5 points (95%CI: 35.6~14.9, I2=52.7%) and the pooled incidence rate to achieve on modified Rankin score (mRS)< or =2 was 40% (95% CI: 30%~51%, I2=35.4%) at follow-up points. The pooled incidence rates of death, seizure, and infection were 13% (95%CI, 8~23%), 15% (95%CI, 8~25%), and 15% (95%CI, 8~23%), respectively. CONCLUSIONS: The published data suggest that stem cell-based therapy for patients with stroke can be judged as effective based on single arm clinical studies. However, clinical benefits of stem cell therapy for patients with stroke need further investigation and reevaluation to test the clinical efficacy.
Arm* ; Follow-Up Studies ; Humans ; Incidence ; National Institutes of Health (U.S.) ; Seizures ; Stem Cells* ; Stroke*

Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4(+) SSEA-1(+)Sca-1(+)Lin-CD45(-) very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (~3-6 microm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells.
Adult* ; Aging ; Antigens, CD15 ; Bone Marrow ; DNA Methylation ; Embryonic Structures ; Genomic Imprinting ; Human Body ; Humans ; Pluripotent Stem Cells ; Regenerative Medicine ; Rejuvenation ; Stem Cells*

Adult stem cells (ASCs) are undifferentiated cells found throughout the body that divide to replenish dying cells and regenerate damaged tissues, which are the powerful sources for cell therapy and tissue engineering. Bone marrow-derived mesenchymal stem cells (BMSCs), adipose tissue-derived mesenchymal stem cells (ADSCs), and peripheral blood monocytes (PBMCs) are the common ASCs, and many studies indicated that ASCs isolated from various adult tissues could be induced to hepatocyte-like cells in vitro. However, the isolation, culture protocols, characterization of ASCs and hepatocyte-like cells are different. This review aims to describe the isolation and culture procedures for ASCs, to summarize the molecular characterization of ASCs, to characterize function of hepatocyte-like cells, and to discuss the future role of ASCs in cell therapy and tissue engineering.
Adult ; Adult Stem Cells* ; Cell- and Tissue-Based Therapy ; Humans ; Mesenchymal Stromal Cells ; Monocytes ; Tissue Engineering

Patients with diabetes have many different kinds of complications involving multiple organs, but those involving the musculoskeletal system are relatively uncommon. Diabetic muscle infarction (DMI) is a rare, painful, and potentially serious condition in patients with poorly controlled diabetes mellitus. A 35-year-old man diagnosed with type 2 diabetes eight years ago, visited with severe muscle pain in the right anteromedial thigh without any event of trauma. He had been treated with metformin, but his glycemic control was very poor with a glycated hemoglobin of 14.5%. Evaluation of his painful thigh lesion did not reveal any evidence of infection or vasculitis, but the magnetic resonance imaging and bone scan showed findings of DMI at vastus medialis muscle and an insufficiency fracture at the right medial tibial condyle. He was diagnosed with retinopathy, neuropathy and microalbuminuria but not macrovascular complications. We also diagnosed his diabetes as latent autoimmune diabetes in adults (LADA) based on his low C-peptide level, positive anti-glutamic acid decarboxylase (GAD) antibody and early onset diabetes. Instead of antibiotics, bed rest, analgesics and strict blood glucose control with multiple daily insulin injections led to symptom improvement. This is an unusual case of a young man with LADA experiencing severe musculoskeletal complication of DMI and insufficiency fracture. If a poorly controlled diabetic patient appears to have unaccounted soft tissue pain, musculoskeletal complications such as DMI associated with hyperglycemia should be considered.
Adult* ; Analgesics ; Anti-Bacterial Agents ; Bed Rest ; Blood Glucose ; C-Peptide ; Diabetes Mellitus ; Diabetes Mellitus, Type 1* ; Fractures, Stress ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Infarction ; Insulin ; Magnetic Resonance Imaging ; Metformin ; Musculoskeletal System ; Myalgia ; Nociceptive Pain ; Quadriceps Muscle ; Thigh ; Vasculitis

Glucocorticoid (GC) excess, including Cushing's syndrome, is a common cause of secondary osteoporosis. Thirty to fifty percent of Cushing's syndrome patients experience non-traumatic fractures, which is often the presenting manifestation of Cushing's syndrome. However, there have been rare cases of Cushing's syndrome diagnosed only based upon bone manifestations. We describe a case of Cushing's syndrome that was diagnosed in a 44-year-old woman who initially visited our hospital due to multiple non-traumatic rib fractures. She did not exhibit any other manifestations of Cushing's syndrome such as moon face, buffalo hump or abdominal striae. Initially, we evaluated her for bone metastases from a cancer of unknown origin, but there was no evidence of metastatic cancer. Instead, we found a left adrenal incidentaloma. As a result of the hormone study, she was diagnosed as having Cushing's syndrome. Interestingly, her bony manifestation of Cushing's syndrome, which was evident in the bone scan and bone mineral densitometry, completely recovered after a left adrenalectomy. Therefore, the possibility of Cushing's syndrome as a cause of secondary osteoporosis should be considered in young patients with non-traumatic multiple fractures, with or without any other typical features of Cushing's syndrome.
Adrenalectomy ; Adult ; Buffaloes ; Cushing Syndrome* ; Densitometry ; Female ; Humans ; Neoplasm Metastasis ; Osteoporosis ; Rib Fractures*