1 Molecular Markers and Networks for Cancer and Stem Cells , Tanabe S*
Stem cell differentiation and self-renewal are regulated by several factors, including molecules that each cell expresses both inside and on its surface. Cancer stem cells (CSCs) exist in some populations of cancer cells, however, the origin and characteristics of CSCs remain incompletely understood; thus, a deeper analysis of the essence of CSCs is required. Since the CSCs exhibit the properties to initiate tumor and be resistant to anti-cancer drugs, inquiries into the molecular mechanisms in CSCs may lead to the discovery of novel therapeutic targets for cancer. Epithelial-mesenchymal transition (EMT), in which cells transit from epithelial-like into mesenchymal-like cell features, is an important phenotype of CSCs and cancer metastasis. In this review article, the molecules and signaling pathways involved in CSCs, with a focus on molecules so-called CD antigens, of which combinations represent cancer types and CSCs, are summarized and described for further investigation of CSCs as well as the stem cell properties of cancer. Considering that CSCs and stem cells may have similar properties, and cancer and stem cells exhibit similar signaling pathway activation in self-renewing, the phenotypes of CSCs including EMT may confer tumorigenic properties to the stem cells. From overviewing the literatures, it is suggested that CSCs are defined with combinations of several markers, and investigation of EMT network is important.
2 Role of Cell Therapy for Patients with Chronic Critical Limb Ischemia to Prevent Amputation , Moniruddin Chowdhury*
Peripheral arterial disease (PAD) is a condition where lumen of peripheral arteries are interrupted, narrowed or completely blocked. Reasons of PAD are Buerger’s disease (Thromboangitis Obliterans, TAO), Atherosclerotic Obliterans (ASO) and connective tissue diseases.
3 Basics of T Cell Development and Activation , Awadhesh KA*
T cells are defined by their development in the thymus from bone marrow-derived precursors and by heterodimeric receptors allied with the proteins of the CD3 complex. Mature T cells leave thymus and migrate into the peripheral lymphoid organs whereupon encounter with the fragment of foreign antigen proteins which are displayed by major histocompatibility complex (MHC) on the surface of antigen presenting cell (APC), they are activated and differentiate into effectors and memory T cells. The adaptive immune responses by T cells are important to protect the host against various types of pathogens. The present review will focus on the basic mechanism involved in the development and activation of T cells.
4 Skin Substitutes. Can these be combined? (Review) , Prezzavento G*
Skin substitutes were developed as an alternative to skin grafts, especially for trauma patients, during the 1980´s.The understanding of the skin components has served as a basis for the development of numerous cutaneous substitutes. A true “skin substitute” would act like an autologous skin graft in adhering to the wound bed while providing the physiological and mechanical functions of normal skin
5 Correlates of Protection against Rotavirus Disease and Immune Response: Need for Further Studies , Tagbo BN*
Rotavirus is a major cause of severe dehydrating acute gastroenteritis especially in infants and young children [1,2]. It is responsible for over 200,000 deaths annually3 and this is only this number following introduction of effective rotavirus vaccines and other preventive measures
6 The Need and Scope for Stem Cell Based Therapy in Hirschsprung Disease , Thambidorai CR*
The role of enteric nervous system in gastrointestinal motility disorders in children has been better understood in recent years. One of the well-researched among these disorders is Hirschsprung disease (HSCR), also known as congenital intestinal aganglionosis. Even with current advances in the surgical management of HSCR significant postoperative morbidity such as defecation problems and enterocolitis occur despite correctly performed surgery. The need for adopting alternate forms of therapy in HSCR disease is well realized and stem cell therapy may provide this path in future. The understanding of embryology of neural crest stem cells and enteric nervous system progenitor cells and their migration to locations in the gut provided the early clues for stem cell therapy in HSCR. Identification of these cells in postnatal tissues at various anatomical locations including the intestines of infants, children and even patients with HSCR has provided the impetus for more intense research in this area. The autologous source of neural crest stem cells from the gut of HSCR patients is a major development in not being immunogenic. Despite these advances, several issues still remain to be solved before adoption of stem cell therapy for HSCR in humans. This mini-review highlights the current status and future directions of the role of stem cell therapy in therapy of HSCR.
7 The Influence of Hypo- and Hyperthyroidism on Morphogenesis and Histophysiology of Adrenal Glands , Yashchenko A* and Lutsyk S
Survey of literature concerning the influence of thyroid hormones imbalance on morphogenesis and histophysiology of adrenal glands. Elevated levels of thyroid hormones induce an increase in the adrenal cortex and subsequent hypercorticosteronemia due to stimulatory effect of thyroxine on the proliferation rate of adrenocorticocytes accompanied with increased density of vascular bed and increased secretion of catecholamines by chromaffine cells. Hypothyroidism induce significant decrease of adrenal cortex, with subsequent decrease of corticosteron production. Maternal hypothyroidism is associated with the delay in maturation of progeny adrenal glands. Both hypo- and hyperthyroidism claim for alterations in adrenal cells ultrastructure.
8 A Brief Communication on a Cell Line of Neural Stem Cells B50 Cells Treated With a New Cisplatin-Based Drug , Ferrari B, Astesana V, De Pascali SA, Fanizzi FP and Bottone MG*
The B50 neuronal cell line was derived, in the 1974, from neuroblastoma in the neonatal rat central nervous system (CNS), and to date it's a cell line widely used in different studies. B50 cells offer several advantages to researchers for the study of CNS neurons in culture: they are simple to grow, to differentiate and to transfect.
9 Immune Cells in the Tumor Microenvironment and Cancer Stem Cells: Interplay for Tumor Progression , Deshmukh SK*
Cancer is one of the leading causes of deaths worldwide due to poor clinical outcome attribute to ineffective treatment and resistance to therapy. Cancer stem cells (CSCs) which have the ability to give rise to all the cell types present in particular cancer believed to responsible for therapy resistance.
10 FOXP1 and ARID3A Collaborate to Activate Transcription of Core Embryonic Stem Cell Factors in Activated B-Cell Diffuse Large B cell Lymphoma , Deng W, Dekker JD, Rhee C and Tucker HO*
Embryonic development requires establishment of networks of stem cells via coordination of “Core” transcription factors (OCT4, SOX2, KLF4, NANOG and c-MYC; abbreviated as OSKNM) with a complex array of auxiliary and epigenetic modulators. We showed previously that down regulation of the ARID3A transcription factor is critical for embryonic stem cell (ESC) growth and differentiation to trophectoderm via direct transcriptional repression of OSKNM. FOXP1 and ARID3Aare two differentially expressed genes that define the most aggressive, Activated B Cell subset of Diffuse Large B Cell Lymphoma (ABC-DLBCL). FOXP1, a well-documented “gold standard of the ABC-subtype, more recently was identified as a regulator of pluripotency, whereas ARID3A function in ES biology is well documented. We demonstrate here that ARID3A is a directly activated target ofFOXP1. Reduction of ARID3Aexpression in ABC-DLBCL tumors, but not in the more benign, Germinal Center (GCB-DLBCL) subset, leads to loss of proliferation and down regulation of several OSKNM factors. Our results suggest that modulation of ARID3A levels may provide both prognostic and therapeutic options for a malignancy representing the most prevalent and aggressive non-Hodgkin's lymphoma worldwide.
11 The Role of β-catenin in Embryonic Stem Cell Maintenance Circuits and iPSCs - An International Systems Biology Approach of Open Science and Innovation , Roman Anton*
Embryonic stem cells (ESCs) and induced pluripotent stem cell (iPSCs), i.e. somatic body cells reprogrammed into ESCs, are the most powerful sources of regenerative medicine. Pluripotency of iPSCs and ESCs bears the capacity to enable all possible cell and organ replacement strategies for regenerative and rejuvenating medicine. This cellular ability is unique and maintained under self-renewal culture propagation conditions that enable intracellular signaling mediators to stabilize the molecular circuits and functions of pluripotency via transcriptional and epigenetic mechanisms inter alia. Understanding these sustained networks that auto-equilibrate in steady states of reciprocatively regulated pluripotency factors that globally organize the stemness genome, transcriptome, and proteome, is crucial for future strategies of regenerative medicine. All stem cells are regulated by such stemness and differentiation circuits and ESC pluripotency is still their best model system. A self-sustaining network of transcriptional activators and repressors specifies the undifferentiated identity and gatekeeps differentiation via hierarchical master regulators like Oct-3/4, Nanog, Sox-2, and Klf-4 at its core. These factors are of the highest functional-regulatory order and can even globally reprogram specialized body cells into iPSCs. The mechanisms of stemness and differentiation are key to decode the postgenomic program of life and its overall complexity represents a new organizational challenge for system biology and open science, which will help to generate cell-based replacement materials and to heal genetic diseases like cancer. As a proof-of-principle, this work further analyzes the role of the signaling mediator β-catenin in stemness and pluripotency and reveals new transcriptional modalities, which further exemplifies the requirement to dissect all multi-functionalities in an open systems biology approach of open science and innovation, and proposes a stem cell hub termed iStemCore.
12 Role of Stem Cells in Cerebral Infarction , Tharshyini Selvi S and Pradeep P*
Cerebral ischemia which may lead to brain tissue damage is one of the leading causes of mortality and physical disability in the world. Transplantation of stem cells has been proposed to be one of the effective therapies for a number of neurological disorders. The ability of stem cells to differentiate into various cells has been explored so that these cells can be beneficial for the use in regenerative therapy. Mesenchymal stem cells which have the ability to promote neurogenesis are currently the promising donor cells for the cure of cerebral infarction. These cells have been reported to show functional proliferation of neurons as well as inhibiting neuronal apoptosis. Exogenous stem cells from various sources can generate neural cells and strengthen the synaptic connection after cerebral infarction. Among all the stem cells, bone marrow derived mesenchymal cell transplantation has been shown to be effective in the treatment of cerebral ischemia. Besides transplantation of stem cells, endogenous enhancement of neural stem cells can also promote neurogenesis. Since neural stem cells are located in the subventricular zones and in the hippocampus of the brain, proper stimulation of these area could enhance neurogenesis in vivo. Both P13k pathway and electrical stimulation are synergistically required to overcome the acute and chronic phases of cerebral infarction. Therefore, sufficient clinical trials should be done to obtain evidence so that stem cell therapy can be used for regenerative therapy in future as these cells have shown remarkable potential in the regeneration of functional neurons.
13 Perfluoro Curcumin Strongly Interacts with ABC Transporter (ABCG2): A Molecular Docking Study , Raviteja CN, Sharma S, Bhardiya S, Bhardwaj V, Chandel V and Kumar D*
Cancer stem cells remain one of the most common reasons for drug resistance and therapeutic failure. The membrane transporter protein ABCG2 has been shown to be over expressed and efflux anti-cancer drugs from cancer stem cells. Despite therapeutic development, the cancer drug resistance and tumor recurrence have increased dramatically in last few years. Thus, identification of potential inhibitor for ABCG2 can be an effective therapeutic approach for cancer through targeting cancer stem cells. In this article, we have performed molecular docking between Curcumin derivatives and ABCG2. Perfluoro Curcumin out of 29 Curcumin derivatives showed highest binding energy, -10.1 kcal/mol with ABCG2, suggest that the Curcumin derivative can be used an effective inhibitor against ABCG2. Perfluoro Curcumin strongly interacted with the ABCG2 at their ligand binding site through hydrophobic interaction. These findings shed light on the molecular characteristics of the binding of Curcumin derivatives with ABCG2 and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer through targeting cancer stem cells by using these agents.
14 Effect of Administration of Acrylamide and Possible Protective Role of Vitamin E on Postnatal Rat Liver Structure , Hegazy AA*, Morsy MM, Shehata MA and Agaga RA
Aim of Study: This study aimed to reveal the structural changes occurring in the liver of albino rats in the postnatal ages after oral administration of acrylamide (ACR) to their pregnant mothers and also to evaluate the protective role of vitamin E (VE). Methods: Fifty-four pregnant rats were equally divided into three groups: control; ACR-treated (received 10mg/kg/day by gastric gavage) and ACR+VE treated group (received ACR plus vitamin E, 100mg/kg/day daily). Treatment was given from day 7 of gestation till weaning. Pups were divided into two subgroups; postnatal days 1 and 21 (D1 and D21). Liver was processed for hematoxylin and eosin (H&E), Mallory stain, caspase 3 and electron microscopic (EM) examination. The mean area percent of collagen fibers and positive caspase 3 reactions were measured. Results: The ACR-treated subgroups at D1 and D21 revealed degenerative changes of hepatocytes. There were congested dilated central and portal veins, bile duct proliferation, marked increase of collagen fibers, strong positive reaction for Caspase 3 and electron-lucent areas of the cytoplasm of hepatocytes, with many vacuoles and shrunken electron-dense nuclei. On the other hand, the protective group receiving ACR plus VE showed some improvement of the histological and morphometric findings. Conclusion: Acrylamide caused marked hazardous impact in the liver of postnatal albino rats. Fortunately, concomitant administration of vitamin E might protect the liver.
15 Impact of the Trivedi Effect®-Energy of Consciousness Healing on the Proliferation of Plant, Mouse and Human Stem Cells , Trivedi MK and Jana S*
The objective of the present study was to evaluate the effect of Biofield Energy Healing on the plant callus, mouse and human derived Mesenchymal Stem Cells (MSCs) for their cell count and cellular proliferation. All the three type stem cells and DMEM media for the stem cell culture were divided into two parts, one received Biofield Energy Treatment (known as The Trivedi Effect®-Energy of Consciousness Healing Treatment) by a renowned Biofield Energy Healer, Mahendra Kumar Trivedi through the Healer’s unique Energy Transmission process remotely and defined as Biofield Energy Treated (BT) group. On day 9 after treatment, the plant callus flasks of mandukparni, amla, and Centella were observed and visualized which showed an increased percentage in weight of the callus by 11.4%, 24.9%, and 51.7%, respectively as compared with the untreated groups. In addition, stem cell assay in murine bone marrow derived Mesenchymal Stem Cells (MSCs) showed an increased cellular proliferation by 115.2%, 127.6%, 161.9%, and 123.6%, in Biofield Energy Treated DMEM in the passage 1, 2, 3, and 4, respectively. Similarly, human derived Mesenchymal Stem Cells, AdiposeDerived (AD-MSC) cells showed a significant increased cell count by 139%, 119%, and 182% in the Biofield Energy Treated DMEM group with the passage 1, 2, and 3, respectively. Similarly, bone marrow (BM-MSC) cells showed a significant increased cell count by 102%, 170%, and 141% in the Biofield Energy Treated DMEM group with the passage 1, 2, and 3, respectively. However, BrdU assay for % cellular proliferation in the AD-MSC cells showed a significant increased cellular proliferation by 122%, 120%, and 184% in the passage 1, 2, and 3, respectively. On the other hand, BMMSC cells showed a significant increased cellular proliferation by 125%, 146%, and 157% in the passage 1, 2, and 3, respectively. Hence, the results suggest that there was a significant growth in plant callus weight, mouse and human stem cell growth and proliferation after The Trivedi Effect®-Energy of Consciousness Treatment. It can be concluded that The Trivedi Effect® can be used as a complementary and alternate therapy for the stem cells regeneration, improvement of tissue injury that might be every effective against various autoimmune human diseases such as arthritis, osteoarthritis, and different neurodegenerative disorders.
16 Challenges of Anaesthesia for Excision of Parasagittal Meningioma in a Diabetic Hypertensive: What are the Lessons? , Chinwe O* and Ephraim O
Parasagittal meningioma complicated by diabetes mellitus and hypertension is a challenging disease. We present the case of a 55-year-old known diabetic hypertensive who presented to us on referral with a diagnosis of intracranial meningioma for neurosurgical care. He was worked up and successfully underwent a craniotomy and total tumor excision. Histology was in agreement with our preoperative concerns. The anesthetic challenges in the management of the patient are discussed.
17 The Role of Genetic Mutations in Gene MTHFR in Anencephaly Syndrome , Shahin Asadi*
Anencephaly syndrome is a genetic disorder that prevents normal growth of the brain and skull bones. This condition can break down the tissues of the nervous system. As a result, people with an anencephaly syndrome lose a large portion of the brain called cerebellum and cerebellum. Anencephaly is a complex disease that is probably caused by the interaction of several genetic and environmental factors. The most known gene for this syndrome is the MTHFR gene, which is based on the short arm of chromosome 1 as 1p36.22.
18 The Effects of Stem Cells on Amyotrophic Lateral Sclerosis , Willis A and Gallicchio VS*
Amyotrophic lateral sclerosis (ALS) is an incurable, cataclysmic motor neuron disease deteriorating the central nervous system. ALS typically has an onset between the ages of fifty to seventy-five with a higher prevalence in white males. The deterioration causes patients to gradually lose voluntary motor abilities to speak, eat, breathe, or move. The main cause of death with ALS is associated with respiratory failure within three to five years of diagnosis. The two pharmaceutical therapies for ALS approved by the FDA are the drugs of Riluzole and Edaravone, however, there has been limited success using this drug therapy. Currently, research using stem cell treatments of Neural Stem Cells (NSC), Human Bone Marrow, Mesenchymal Stem Cells (MSC), Induced Pluripotent Stem Cells (iPSCs), and Human Umbilical Cord Blood Cells (HUCBC) have been projected as an alternative new therapeutic approach. In addition, there are promising results with the addition of lithium to stem cell therapy as a potential therapy for ALS. Stem cell therapy for ALS uses the SOD1G93A transgenic mice model. Human trials using stem cells have been conducted, but additional clinical studies need to be conducted in order to determine the most beneficial stem cell therapy for patients with ALS.
19 Evaluation and Identification of Celiac Disease Associated Antigen DQ2 and DQ8 in Northern Indian-Kashmir Valley , Rasool R#, Kawoosa F#, Qazi AK* #, Ahmad M, Masoodi M, Sultan T, Beigh AH and Shah ZA
Background: Celiac disease (CD) is a commonly occurring food gluten sensitive enteropathy characterized by smallintestinal mucosal injury and nutrient malabsorption. It is known in genetically susceptible individuals by the ingestion of wheat gluten and similar proteins of other cereals, inducing an abnormal immune response. The genetic susceptibility of CD is associated with specific Major Histocompatibility Complex (MHC) II alleles that encode human leukocyte antigen (HLA) DQ2 or HLA DQ8 heterodimers. Aim of Study: The present study was aimed at identification and evaluation of HLA “DQ2” and “DQ8” heterodimers in human subjects and determination of prevalence of Celiac disease in Kashmiri population. Methodology: A total of sixty symptomatic clinical cases comprising of twenty five (25) males and thirty five (35) females were included in this study. The typing of HLA alleles was carried out by employing Sequence Specific Primers (SSP)-PCR. Results: Our results demonstrated that among sixty participants, percentage of DQ2+/ DQ8+, DQ2+/DQ8- , DQ2-/DQ8+ and DQ2-/ DQ8- were 11.66%, 53.33%, 8.33% and 26.66%. Moreover, among the twenty five male participants, five were DQ2+/ DQ8+, ten DQ2+/ DQ8- , two DQ2-/ DQ8+, and eight DQ2-/ DQ8- . Similarly, among thirty five female participants, two were DQ2+/ DQ8+, twenty two DQ2+/ DQ8- , three DQ2-/ DQ8+, and eight DQ2-/ DQ8- . Furthermore, our results also revealed that among the sixty participants, twelve (20%) participants had low, fourteen (23.33%) participants have high, eighteen (30%) participants have very high and sixteen (26.67%) participants have no susceptibility to celiac disease. In terms of gender predisposition we found that male subjects were 28% and females 45% susceptible to celiac diseaseConclusion: From the current study we establish that majority of the subjects under study are susceptible to celiac disease and notably females are more susceptible as compared to males. Findings of the recent work could possibly aid in better understanding the prevalence of CD in Jammu and Kashmir. The high ratio of CD in females than males is also a question of future research.
20 The Optimal Isolation and Characterization Conditions of Rabbit Dental Pulp-Derived Mesenchymal Stem Cells for Use in Regenerative Medicine , Salkin H*, Gonen ZB, Ozcan S, Bahar D, Kutuk N and Alkan A
Background and Objectives: Currently, dental pulp stem cells have gained importance in stem cell research. Our aim was to isolate mesenchymal stem cells from the rabbit dental pulp and to characterize those using different methods. Methods: Mesenchymal Stem Cells (MSCs) were obtained by enzymatic method from dental pulp of New Zealand Rabbits. MSCs that were derived from rabbit dental pulp (rabbit DPSCs) were characterized by using flow cytometry, immunofluorescence staining, quantitative Real Time PCR (qRT-PCR). For the characterization, CD29, CD44 and CD45 MSC markers were used. Adipogenic, osteogenic and chondrogenic differentiation tests were performed for multilineage differentiation. The clonogenic properties of the obtained rabbit DPSCs were demonstrated by the Colony forming unitsfibroblast (CFU-F) Test. The results were analyzed statistically. Results: Flow cytometry, immunofluorescence staining and qRT-PCR analysis showed that rabbit DPSCs were positive for CD29 and CD44 antibodies; and negative for CD45 antibody (p<0.001). Adipogenic, osteogenic and chondrogenic differentiation was demonstrated by adipo-red, alizarin red, alkaline phosphatase and safranin-O positive staining. In the CFU-F test, 127.7±13.98 colonies and 211.3±10.40 colonies were counted at 500 cells/well and 1000 cells/well, respectively (p<0.001). Conclusion: rabbit DPSCs have been successfully isolated from rabbits; and it has been proven that the cells obtained are MSCs. It has been determined that there are high potency cells according to other stem cell sources. Rabbit is a model organism frequently used in in vivo studies. Hence, rabbit dental pulp stem cells can be used in both in vitro and in vivo clinical, surgical and tissue engineering studies.
21 Primary Refractory Double Hit Diffuse Large B Cell Lymphoma: Complete Response to Ibrutinib and Rituximab , Kamble RT*, Obi G, Manhas A and Carrum G
Double hit lymphoma (DHL) associated with translocations in MYC and BCL-2 or BCL-6 gene accounts for approximately 5-10 % of all diffuse large B cell lymphoma (DLBCL) [1]. These patients are distinct from double-expressers who stain positive on immunohistochemistry for MYC and BCL2 or BCL6 accounting for approximately 25-35% of all DLBCL
22 Growth Differentiation Factor 11 (GDF11)/Transforming Growth Factor-β (TGF- β)/Mesenchymal Stem Cells (MSCs) Balance: A Complicated Partnership in Skin Rejuvenation , Mazini L*, Rochette L and Malka G
Different theories on how cells aged and many strategies to overcome this have been thought and retained much more attention in designing research in tissue regeneration and skin anti-aging. Mesenchymal stem cells (MSCs) have showed great interest since identified as residual stem cells in almost adult organs. These cells presented great ability in migration and were recruited rapidly into wounded sites where process of cell differentiation towards various skin cell components occurred. MSCs senescence may be involved in the loss of tissue homeostasis, which could lead to organs failure and development of age-related diseases. Several studies have demonstrated that intravenously injected MSCs can migrate specifically to the sites of tissue damage, such as those caused by ischemic conditions or inflammation. A continuous state of inflammation in the wound creates a cascade that perpetuates a nonhealing state. During the inflammatory phase, MSCs coordinate the effects of inflammatory cells and inhibit the deleterious effects of inflammatory cytokines. Different proteins are secreted by these cells such as vascular endothelial growth factor (VEGF), Transforming Growth Factor-β (TGF-β), and Growth Differentiation Factor 11 (GDF11) are the key tools for ensuring tissue regeneration. The mechanisms inducing tissue degeneration and cell aging remained multifactorial and still unclear. The skin undergoes constant changes, with a high capacity of repair and renovation. In wound healing, evidence established the involvement of MSCs and dermal fibroblasts (DF) through sirtuins and SMAD pathways. Moreover, the mainly and recently studied secretome of MSCs is the extracellular vesicles involved in migration and proliferation of DF and keratinocytes where GDF11 and TGF-β were expected to play the principal role. Theoretically identical MSCs populations from individuals may display different secretome properties, depending on factors including age and health status. Another source of adult stem cells, called adipose-derived stem cells (ADSCs), is relatively newer and less invasive with a similar cell differentiation potential. Further in-depth studies are needed to clarify the relationships between these factors in promoting wound healing and antiaging process. These new approaches might be adapted for various cell types and the specific secretome promising for application in regenerative medicine.
23 Postnatal Changes in the Structure of Rat Testis , Hegazy AA, Ahmad MM, Aziz JA and Abd Almotaleb NA*
Background: Postnatal development of rats' testes passes through stages. Elucidation of changes occurring at each age stage is essential to recognize any pathological deviation. Aim: It was to investigate the histological and ultrastructure features of the rats' testes at different postnatal stages. Methods: Eight healthy non-pregnant adult female albino rats weighting 150-250 gm were brought to be pregnant. Their male pups were divided into four groups (10 each), according their postnatal day (PND) at the time of scarification as follows: group I, II, III and IV at 1st, 21st, 35th and 70th PND respectively. The testes were dissected and processed for both light microscope (LM) and electron microscope (EM) investigations. Results: Neonatal rat testis (group I) was formed of seminiferous cords containing gonocytes and immature Sertoli cells. The gonocytes or fetal germ cells were the most prominent finding in 1st PND within the non-canalized seminiferous cords. At PND 21 (group II), tubular diameter was increased with appearance of rounded spermatid at PND 26. The cell layers of the lining epithelium of the tubules were formed of spermatogonia, Sertoli cells and primary spermatocytes with large rounded cells with clumped chromatin. At PND 35 (group III), the tubular diameter was increased and showed more stratification of their epithelial lining with increased tubular cell layers. At PND 70 (group IV), the testis was formed of large seminiferous tubules, closely packed together. Conclusion: Development of testis is a continuous process in postnatal life reaching its maximum at sexual maturity “about 2 months of rat birth”.
24 Liver Cells Can Dedifferentiate and Act as Progenitor Cells for Liver Growth , Gupta PD*
Indeed, liver is the largest internal organ that performs major metabolic activities. Liver is a gland and performs both exocrine and endocrine functions. It also possesses the capacity to regenerate. The liver is the only organ that can grow back when part of it is damaged or removed surgically
25 Pt(IV)Ac-POA: New Platinum Compound Induced Caspase Independent Apoptosis In B50 Neuroblastoma Stem Cells , Ferrari B, Camuso S, Priori EC, De Luca F, Roda E, Osella D and Bottone MG*
Neuroblastoma is a tumour that affects adults and children, characterized by a stem cells component. To date, cisplatin is the main antitumor agent used in the clinical treatment of this tumour; however, it induces side effects such as neurotoxicity in healthy cells and induces chemo resistance to therapy in cancer cells. New platinum-based compounds, platinum (II) have recently been synthesized, and due to their chemical characteristics, they are able to identify new cellular targets. These complexes act as prodrugs and performing their cytotoxic effect as platinum (II) after a reduction reaction within the hypoxic tumour cells. Among these prodrugs, Pt(IV)Ac-POA appears to be very promising, thanks to the presence of ligand (2-propinyl)octanoic acid (POA), which acts as an inhibitor of histone deacetylase (HDACi) and leads to the increase of histone acetylation, decreasing the interactions between histone and DNA, so as to produce chemo-sensitization to DNA-damaging agents. The greater cytotoxic effect of Pt(IV)Ac-POA on tumour cells, would therefore be mainly due to the mechanism of inhibition of histone deacetylase, which would increase the accessibility of DNA to platination mechanisms that induce cell death. In this study the results show that Pt(IV)Ac-POA, used at a concentration ten times lower than cisplatin, can induce apoptosis in B50 cells in culture both through the intrinsic pathway and through the independent caspase pathway. The data, obtained by immunohistochemical techniques in fluorescence microscopy, show that treatment with Pt(IV)Ac-POA has a greater proapoptotic effect on stem cells compared to the cisplatin standard treatment.
26 In Vitro Germ Line Differentiation from Pluripotent Stem Cells , Yang M*
Germ cells carry hereditary information and genetic diversity. The production of functional germ cells is a key component of successful reproductive processes
27 Safety and Efficacy of a Combination Therapy (Autologous Bone Marrow Derived Mononuclear Cells and Umbilical Cord Derived Mesenchymal Stem Cells) in Duchenne Muscular Dystrophy Patients , Rajput B*, Meher K, Somalapur P, Kulkarni R, Bopardikar A and Kumar R
Duchenne muscular dystrophy is a neuromuscular disorder caused due to mutations in dystrophin gene. It is characterized by progressive muscle degeneration; cellular therapies pose as a possible treatment option for this debilitating disorder. Earlier many cellular therapies with autologous and allogenic stem cells have provided evidences of their efficacy in the treatment of DMD. This study was carried out in different hospitals of India to prove the safety & efficacy of combination of autologous and allogenic stem cells in DMD patients. 30 patients were enrolled of which 18 were in the treatment group and 12 in the control group. Patients from each treatment group were given 4 sessions; 1 with autologous BM-MNCs and 3 with allogenic UC-MSCs. Assessments were done on the basis of Muscle strength, Functional Independence scale, Brooke and Vignos scales. Among the treatment group, 77.7% patients showed positive response. There was 63% and 50% rise in upper and lower limb’s power respectively after the completion of the protocol in the treatment group. When control group (n=12) was compared with treatment group (n=18), it was observed that the muscle strength in upper and lower limbs declined from the baseline by 41% and 47% respectively. Furthermore, Functional-Independence Measure score and Brooke-Vignos score also improved, suggestive of the efficacy of the treatment
28 Comparative Study on the Effect of Adipose-Derived Stem Cells Versus Alpha-Lipoic Acid Inautologus Fat Graft Survival , Ibrahim SH, Sahar MMO*, Khalek Ibrahim GAE and Omar AE
Autologous fat transfer is a popular option for soft tissue augmentation, but has a low survival rate. So, enriching the transplanted fat with stem cells (cell assisted lipotransfer) or oral administration ofalpha-lipoic acid (ALA) before and after graft injection, were thought to increase the survival rate of the transplanted fat. Aim of Study: Is to compare between cell-assisted lipotransfer (CAL) and ALAtherapy in improvement of fat graft survival. Materials and Methods: Thirty adult female albino rats were used and divided into three groups. Group I: the control group. Group II: CAL group received autologous fat mixed with adipose derived stem cells (ASCs). Group III: ALA group in which animals received oral ALA four days before fat transplantation and continued throughout experiment. Fat grafts were collected from the sites of injection after twenty-eight days. Histological and immune histochemical studies were performed. Statistical analysis was also done. Results: Histological evaluation revealed atrophy and death of adipocytes with formation of fat cysts. Severe inflammatory infiltration with giant cells formation and fibrosis were detected. Significant decrease of VEGF reaction was seen. In CAL group significant increase in number of intact adipocytes together with decrease in inflammation and fibrosis occurred. Moreover, significant increase in VEGF reaction was observed. In ALA group, significant decrease in number of intact adipocytes and VEGF reaction was detected compared with CAL group. Also, significant increase in inflammatory infiltration and fibrosis were detected compared to CAL group. Conclusion: Both ASCs and ALA showed improvement in all histological parameters compared with control group. However, enrichment of fat with ASCs showed the best results.
29 Major Technology and Business Trends Empowering Stem Cell Reprogramming , Cauwenberghe CV*
The advent of stem cells reprogramming commenced with the discovery of the differentiation factors that allow the creation of human iPSCs (hiPSCs). Today, researchers all around the world are strongly committed to develop novel methods to design and build human stem cells in order to meet the increasing demand for more efficient production systems and manufacturing methods of stem cells for potential investigation into disease management. This trend is emphatically envisaged to accelerate the development of both regenerative medicine and drug discovery and development.
30 Mid-Term Clinical Outcomes of Intraarticular Injection of Platelet Rich Plasma and Adipose-Derived Mesenchymal Stem Cells for the Treatment of Intra articular Pathology of the Knee, Hip and Shoulder , Steele JR, Boggess BR*, Finley S and Reinke E
Introduction: Intra articular injections of platelet rich plasma (PRP) and adipose-derived mesenchymal stem cells (ADMSCs) have individually shown potential benefit in the treatment of intraarticular pathology of the knee, hip and shoulder. However, outcomes data is sparse in regards to PRP and AD-MSCs injected in the same setting. The purpose of this study is to assess the midterm clinical outcomes and safety profile of intraarticular injection of PRP and AD-MSCs into arthritic hips, knees and shoulders. Methods: After IRB approval, a retrospective chart review identified 50 patients who had received intraarticular injection of PRP and AD-MSCs into their hip, knee or shoulder for intraarticular pathology. Clinical outcomes including the need for further injections, progression to surgery and any adverse effects were collected. Patient reported outcomes scores and patient satisfaction were collected at average 2-year follow-up for 39/50 patients (78%). Results: Clinical outcomes were favorable at 2-year follow-up. Approximately 70% of people were satisfied with the results of their treatment overall. Only 4% of patients progressed to repeat PRP and AD-MSC injection into the joint of interest while 21% of patients progressed to surgery. There were no significant adverse events encountered during the 2- year period. Median improvement in clinical outcome scores was above the minimally clinically important difference. Conclusion: Intraarticular injections of PRP and AD-MSCs into hips, knees and shoulders are safe and have a low rate of progression to further surgery or repeat injection at 2-year follow-up. Improvement in clinical outcome scores and high patient satisfaction were demonstrated at 2-year follow-up.
31 The Development of Tumor Heterogeneity and Actively Targeting Therapy Resistant Subpopulations , Chandel V and Kumar D*
Tumor heterogeneity refers to the coexistence of cellular subpopulations bearing different epigenetic or genetic alterations within the tumor as a whole (intracellular tumor heterogeneity) and in different cells of the same patient referred to as secondary tumors/metastatic sites. This is clinically relevant because the bulk tumor mass may comprised of collection of cancer cells with varying levels of sensitivity to treatment and distinct molecular signatures. Tumor heterogeneity can also exist between the same cancer from different patients (inter-tumor heterogeneity) and within a single tumor (intra-tumor heterogeneity). Cancer cell heterogeneity introduces emerging challenges in classifying patients that might benefit from specific therapies or using molecular prognostic markers. Thus efforts in research for characterizing heterogeneity would be useful for a better understanding of the causes and progression of the disease. In the field of molecular diagnostics constituting tumor genotyping and blood based methods, recent advances allows the detection of clonal evolution in patients suffering from cancer.
32 The Advantages of Using Mesenchymal Stem Cells in the Treatment of Massive Burns-Case Report , Oproiu AM* and Grigore A
Due to insufficient oxygenation of tissues, cellular and vascular destruction, burns show a different healing process from other wounds. Even if it affects only one organ, namely the skin, it can generate a systematic response in which multiple organs are affected, with high risk of infections and mortality. Therefore it represents a challenging pathology with the involvement of several specialties, which, depending on the way of production, the surface and the depth of the burn, requires special care, long hospitalizations, and multiple surgical interventions. Even if with the evolution of the medicine, the mortality of burns was also improved, the healing process is often unsatisfactory with negative consequences on the functional and physical aspects, which reduce the quality of the patient’s life. This work paper aims to present a different approach in the management of a II-III degree burn, of approximately 20% body surface, at the level of the posterior thorax and the left upper extremity, using mesenchymal stem cells. The procedure involved the collection of skin samples with a diameter of 5 mm each one, match them with saline solution, introduce them in a special device, disaggregate them and inject the resulting suspension solution rich in mesenchymal stem cells into the dermis with the advantage that it can skip over the excisional debridement stage and decrease significantly large skin graft donor areas of the standard approach, and other possible surgical interventions subsequent.
33 Expression of TNF-Α and IL-1β Messenger RNA in Stem Cells of Normotrophic and Hypertrophic Scars , Alcantara Quintana Luz Eugenia*, Garcia Ruiz Gilberto F, Teran Figueroa Yolanda, Rodriguez Fuentes Nayeli, Benitez Arvizu Gamaliel
Introduction: Post-burn hypertrophic scar tissue (Hsc) is characterized by increased collagen synthesis, cellular growth (hyperplasia) and cell turnover (shedding). Its clinical characteristics (erythema, pain, dysesthesia, pruritus, elevation) exhibit aspects of chronic local inflammation, but the mechanism of its etiopathogenesis has not been clearly elucidated. In chronic skin inflammation, pro inflammatory and profibrogenic cytokines play an important role in producing skin dysfunction. In this study, we examined changes in tumor necrosis factor (TNF)-α and interleukin (IL)-1 β mRNA expression and its presence in post-burn hypertrophic scars in stem cells. Results obtained in normotrophic scar tissue (Nsc) were compared to results obtained in normal skin (Ns). Materials and Methods: Skin biopsies were obtained from 15 patients with (Hsc) who presented burns on over 10% of their skin surface, more than a year post-injury. Nsc was obtained from 17 patients who experienced scarring in optimal conditions. Ns were obtained from 11 patients who underwent cosmetic or reconstructive surgery. We performed histopathology analysis with routine processing. TNF-α and IL-1β mRNA expression levels on all three types of biopsy were obtained via semi-quantitative RT-PCR, RT-qPCR, western blot and by in situ hybridization. Results: When analyzing mRNA expression levels by semi-quantitative RT-PCR, and qPCR we observed higher TNF-α and IL-1β levels in post-burn hypertrophic scar tissue relative to normal skin and normotrophic scar tissue. In contrast, in situ hybridization revealed significant differences in IL-1β hybridization intensity localized in Hsc epidermis relative to Nsc and Ns epidermis. For TNF-α, expression intensity in epidermis and dermis did not differ between Ns, Nsc and Hsc. We found higher TNF-α-positive porcentage of cells in the epidermis of Ns and Hsc relative to Nsc; meanwhile IL-1β-positive percentage of cells were higher in the epidermis of Hsc as compared to Ns and Nsc. Our histopathologic analysis yielded relatively low inflammatory infiltrate cell counts, and we found no correlation between inflammatory infiltrate cell count and cytokines produced. Conclusion: Together these results suggest that there is increase in TNF-α and IL-1β mRNA expression in post-burn Hsc. Interestingly, the basal keratinocytes (stem cells) showed differential expression of both cytokines compared to other cell types, which suggests that they may play an important role in post-burn skin repair processes.
34 A Feminist Scientist Shouts Conveying I Am Here , Montaser LM*
I will narrate my successful experience and research in SPIE 2015 at San Diego, California, USA on a scientific and national level. An Egyptian female scientist’s perspective taking place in San Diego, SPIE conference 2015 was a very successful experience concerning the application of Nano scaffolds and stem cell therapy in liver tissue engineering.
35 Therapeutic Implication of Human Bone Marrow Mesenchymal Stem Cell-Conditioned Medium to Reduce Cystogenic Potential of CD133+ Renal Progenitor Cells of Human Polycystic Kidneys , Ehsan Ehsani, Sara Hajibabaei, Farid Dadkhah and Reza Moghadasali*
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder in which, epithelial cells are somehow dedifferentiated but highly proliferative and form renal cysts. There are also proliferative CD133+ renal progenitor cells in an ADPKD kidney. Among several therapeutic strategies that exist to heal ADPKD, bone marrow mesenchymal stem cells (BMMSC) are of great interest. So, we examined human BM-MSC-condition medium (hBM-MSC-CM) effects on polycystic CD133+ renal progenitor cells. For this purpose, polycystic CD133+ renal progenitor cells were isolated from patients undergoing nephrectomy for kidney transplantation. Differentiation and cystogenic potentials of polycystic CD133+ renal progenitor cells were evaluated using hBM-MSC-CM. Polycystic-lining cells expressed CD133 as a renal progenitor cell marker. These cells were more proliferative and presented a defective epithelial differentiation phenotype compared to normal kidney CD133+ renal progenitor cells. Also, they were not able to express differentiated tubular epithelial cell markers such as E-cadherin and ZO-1. Moreover, polycystic CD133+ renal progenitor cells, in contrast to normal CD133+ renal progenitor cells, formed cysts in a three-dimensional (3D) culture system. hBM-MSC-CM treatment decreased proliferation and cystogenesis, but increased differentiation of polycystic CD133+ renal progenitor cells in vitro. All in all, hBM-MSC-CM could decrease the proliferation and cystogenesis through induction of differentiation in polycystic CD133+ renal progenitor cells.
36 Adipose derived stem cells (ADSCs) Immunomodulation Impact on Skin Tissue Repair , Mazini L*, Rochette L, Amal S, Admou B and Malka G
Adipose derived stem cells (ADSCs) have largely proven their efficiency in wound healing and skin regeneration in vitro and in vivo. They are niched within the hypodermis where they differentiate into skin cell types and migrate to wounded sites to restore cell deficiencies and functions. ADSCs mainly act by an autocrine pathway through their secretome containing growth factors, cytokines and microRNA (miR) involved in their migration and proliferation and that of dermal fibroblasts (DF) and keratinocytes. There are evidences arguing that the immunomodulation capacity of ADSCs reflect their efficacy to ensure skin tissue repair. Their secretome is implicated in immune responses and is considered as the key tool in regulating skin inflammation and diseases-associated inflammation. By their action on skin immune cells, ADSCs are expected to play the principal role by modulating: i: the expression of the inflammatory factors; ii: the activation and maturation of immune cells especially M1 and M2 macrophages and inhibition of Th cells; iii: the skin cell differentiation, proliferation, pigmentation and migration and iv: the secretion of the extracellular matrix (ECM) proteins. Additionally, ADSCs cross-react with the different skin cells, ECM and the surrounding growth factors to initiate and accelerate the implementation of all phases of wound healing. In this review, we highlight the role of ADSCs in deriving tissue repair with regard to their immune-modulation ability, this impressive capacity should be considered when using ADSCs in regenerative medicine.
37 Current Status of Cancer Stem Cell Research , Kereena Chukka*
The purpose of this editorial is to highlight the recent Cancer Stem Cell research contributions and their approaches towards human cancers. Despite of major scientific and technological progress of research & development for new therapeutic advances during the past decade, Cancer remains a significant public health problem
38 Stem Cell Diversity and Therapeutic Aspects of Hyperglycemia , Hasan R, Begum RA, Shahjahan R and Khandaker AM*
Animal body is made up of many different types of cell. Most cells are specialized to perform particular functions. As for instance, the red blood cells carry oxygen around animal bodies through the blood, but they are unable to divide. Stem cells provide new cells for the body as it grows, and replace specialized cells that are damaged or lost.
39 Stem Cells in Urethral Replacement , Thambidorai CR*
Reconstruction of the male urethra has been and remains a challenge in adult and pediatric urology, especially for long urethral defects in the former and re-do surgery for hypospadias repair in the latter. The ability of stem cells for multipotent differentiation and the recognition of urine derived stem cells (USCs) have significantly improved the application of stem cell technology in urology, particularly for the reconstruction of urethra. USCs are recoverable from voided urine and the techniques for their recovery have improved in recent years. Stem cells from the bladder have been successfully seeded on to scaffolds for the regeneration of tubular urethra like structure. Despite these encouraging results, many issues remain in the clinical application of stem cells in urethral regeneration and other urological procedures. These include better understanding of the multiplication potential and direction of differentiation of stem cells, functionality of the tissues generated and avoidance of harmful effects like development of neoplasms. Appropriate choice of the source of stem cells and methods of administration for the different conditions requiring their use need more research. Governing regulations in the use of stem cell therapy is another challenge that requires to be addressed.
40 hPP Corpus: A Tagged Biomedical Corpus for Automatic Extraction of Human Protein Phosphorylation for Understanding Cellular Functions , Raja K, Subramanian D, Abdulkadhar S and Natarajan J*
Proteins perform their functions by interacting with other proteins. Phosphorylation is a post-transcriptional modification of proteins and plays an important role in cellular functions. Protein interaction and phosphorylation play a critical role in biological functions and indicate disease states including cancer, Alzheimer’s disease and Parkinson’s disease. Mining protein phosphorylation information from biomedical literature is a topic of interest in biomedical text mining and highly challenging. Text mining researchers apply a variety of algorithms to extract such information. A standard annotated corpus is necessary to evaluate the performance of the text mining algorithms. However, to our best knowledge there is no standard annotated corpus available for evaluating approaches related to the extraction of protein phosphorylation information related to human. The available corpora, iProLink, PTM (Post Transcriptional Modification) phosphorylation extraction corpus and protein phosphorylation corpus from Protein Information Resource (PIR) are not specific to human. In this paper, we present a corpus called ‘hPP (human Protein Phosphorylation) corpus’ exclusively on human protein phosphorylation information. Current version of hPP corpus contains 2,380 sentences from 1,000 MEDLINE abstracts related to human protein phosphorylation. The corpus is annotated with named entities, event relationship and syntactic dependencies, and freely available at http:// www.biominingbu.org/hPPcorpus/hPP_corpus.xml. To our best knowledge hPP corpus is the first and foremost annotated corpus available for evaluating text mining systems on extracting human protein phosphorylation from MEDLINE abstracts.
41 Stem Cell A Solution beyond the Pandemic Covid-19 the Uncertainty of being able to Move on , Mistrih FG, Mistrih NG and Eghon G*
In a market in Wuhan, China, apparently due to the ingestion of live bats, as part of the culture of the natives, an infection of the virus was generated, which until now has not been effectively treated, which is why we justify expanding our knowledge of a therapeutic alternative that appears, beyond being a preventive treatment, perhaps the solution to this pandemic, the effectiveness of IV mesenchymal cell transplantation, has not been described with conclusive results that allow scientists to propose it as the only treatment, but studies in multiple pathologies show a very favorable immune reaction, modulating inflammatory cascades in inflamed tissues. In addition, it clearly presents a regeneration of it (which is the same) that has powerfully caught the attention of doctors when treating pathologies, autoimmune, degenerative, and chronic pathologies, which to date have had no palliative treatments, such as SLE, post-infarction heart disease, chronic arthritis, Alzheimer’s and among others, many laboratory studies were necessary, due to the urgent need of frustrated patients due to the few therapeutic possibilities that led to the use of mesenchymal cells for their treatment. The pneumonias caused by this new virus are of rapid progression and very lethal, with a treatment of little effectiveness and for this reason we have proposed the regulation of cytosines through the transplantation of mesenchymal cells, being these the main causes of complications due to their increase in the systemic reaction.
42 SAR-COV-2 Pandemic , Eghon G*
Since time immemorial, several centuries before Christ, humanity has faced plagues and pandemics that have decimated the world population, just remember the plague of Athens in 430 BC, several plagues have put human survival. We cannot forget smallpox that killed 300 million people; measles killed around 200 million human beings, the Spanish flu that is estimated at between 50 and 100 million. We have survived the black plague, bubonic plague, diphtheria, yellow fever, malaria, cholera, Ebola, tuberculosis, hanta virus, dengue and one of the most recent HIV, which already as 35 million deaths.
43 Creating the Next Generation Human 2n=44 from Embryonic Stem Cells , Dehghan FK* and Kamalidehghan B
A robertsonian translocation does not always produce harmful results. In fact, many mutations are impartial, and some even reach useful traits. For instance, if balanced carriers are parents 13/21 or 14 /21 or 15/21. This is the start of the new generation of human 2n=44 using In vitro fertilization (IVF). In the chromosomes balanced human 14/21 is relatively prevalent. With the proliferation of the cells, 3-type offspring create Second Human Species as follows: Carriers of balanced parents: 45, XY t (13 /21) X 45 XX t (13/21) → Type 1 - human 2n=44. Carriers of balanced parents: 45, XY t (14 /21) X 45 XX t (14/21) → Type 2 - human 2n=44. Carriers of balanced parents: 45, XY t (15 /21) X 45 XX t (15/21) → Type 3 - human 2n=44. Our study suggested that chromosomal evolution is from a chromosomal fusion, playing a significant role in decreasing the ancestral diploid number to the range of values currently seen.
44 Unusual Termination of the Facial Vein into External Jugular Vein and its Clinical Implication , Lufukuja GJ* Lugwisha P Mwaipaja E and Byabato B
The superficial veins of the neck are used for cannulation, either for intravenous infusion or for central venous pressure monitoring. Variations in the venous system from the normal pattern are relatively common. We present some unusual variations of the facial vein draining into the external jugular vein instead of draining into the internal jugular vein. The external jugular vein usually begins just behind the angle of the mandible by the union of the posterior auricular vein with the posterior division of the retromandibular vein and then descends obliquely across the sternocleidomastoid muscle and, just above the clavicle, pierces the deep fascia and drains into the subclavian vein. External jugular vein gives a reliable estimate of central venous pressure. The variation may give false value of pressure due to facial vein draining into it, also may create difficulty in catheterization. It’s very important not only for anatomists but also for head and neck surgeons to be aware of the possible anatomical variation in the formation of external jugular Vein and its clinical implications.
45 Alzheimer’s Disease and Stem Cell , El Shawarby A and Omar SMM*
Aging causes many changes in the human body, as a mechanism responsible for maintaining proper protein composition starts to decline with age. Proteins lose their stability, and the autophagy process failed, which resulted in the accumulation of misfolded proteins, which in turn resulted in diseases.