Thekkeparambil Chandrabose Srijaya

Advancing stem cell therapy from bench to bedside: lessons from drug therapies

The inadequacy of existing therapeutic tools together with the paucity of organ donors have always led medical researchers to innovate the current treatment methods or to discover new ways to cure disease. Emergence of cell-based therapies has provided a new framework through which it has given the human world a new hope. Though relatively a new concept, the pace of advancement clearly reveals the significant role that stem cells will ultimately play in the near future. However, there are numerous uncertainties that are prevailing against the present setting of clinical trials related to stem cells: like the best route of cell administration, appropriate dosage, duration and several other applications. A better knowledge of these factors can substantially improve the effectiveness of disease cure or organ repair using this latest therapeutic tool. From a certain perspective, it could be argued that by considering certain proven clinical concepts and experience from synthetic drug system, we could improve the overall efficacy of cell-based therapies. In the past, studies on synthetic drug therapies and their clinical trials have shown that all the aforementioned factors have critical ascendancy over its therapeutic outcomes. Therefore, based on the knowledge gained from synthetic drug delivery systems, we hypothesize that by employing many of the clinical approaches from synthetic drug therapies to this new regenerative therapeutic tool, the efficacy of stem cell-based therapies can also be improved.

Unique molecular signatures influencing the biological function and fate of post-natal stem cells isolated from different sources

The discovery of mesenchymal stem cells (MSCs) from a myriad of tissues has triggered the initiative of establishing tailor‐made stem cells for disease‐specific therapy. Nevertheless, lack of understanding on the inherent differential propensities of these cells may restrict their clinical outcome. Therefore, a comprehensive study was done to compare the proliferation, differentiation, expression of cell surface markers and gene profiling of stem cells isolated from different sources, viz. bone marrow, Whartons jelly, adipose tissue and dental pulp. We found that although all MSCs were phenotypically similar to each other, Whartons jelly (WJ) MSCs and dental pulp stem cells (DPSCs) were highly proliferative as compared to bone marrow (BM) MSCs and adipose tissue (AD) MSCs. Moreover, indistinguishable cell surface characteristics and differentiation capacity were confirmed to be similar among all cell types. Based on gene expression profiling, we postulate that BM‐MSCs constitutively expressed genes related to inflammation and immunodulation, whereas genes implicated in tissue development were highly expressed in AD‐MSCs. Furthermore, the transcriptome profiling of WJ‐MSCs and DPSCs revealed an inherent bias towards the neuro‐ectoderm lineage. Based on our findings, we believe that there is no unique master mesenchymal stem cell that is appropriate to treat all target diseases. More precisely, MSCs from different sources exhibit distinct and unique gene expression signatures that make them competent to give rise to specific lineages rather than others. Therefore, stem cells should be subjected to rigorous characterization and utmost vigilance needs to be adopted in order to choose the best cellular source for a particular disease. Copyright

Identification of Diploid and Triploid Red Tilapia by Using Erythrocyte Indices

Abstract The individuals of diploid and triploid red tilapia Oreochromis mossambicus (Peters, 1852) X Oreochromis niloticus (Linnaeus, 1758) were identified by using erythrocyte indices. The major cell and minor cell axis of the erythrocyte were 27.7 and 11.5%, respectively higher in triploids as compared to diploid fishes. The increase in nucleus size of the erythrocytes of triploid was also greater by 31.7% for the major axis and 17.2% for the minor axis with respect to the erythrocytes of diploid fishes. Similarly the increase in nucleus cell surface and volume of the nucleus were also higher by 50.4 and 68.5%, respectively in the triploid fishes as compared to the diploids fishes. Moreover the erythrocyte cell surface area and cell volume of triploids were higher by 42% and 59% respectively to diploid ones. The cytoplasmic volume of erythrocyte cell was also increased by 57.9% in the triploids fishes with respect to diploid individuals. The present study clearly showed that the nuclear volume, cytoplasmic volume and nucleus surface area of the erythrocytes are significantly greater (p < 0.005) in the triploids as compared to the diploid fishes. These parameters thus can successfully be used in discriminating diploid and triploid red tilapia.

A Simple Technique for Chromosome Preparation from Embryonic Tissues of teleosts for Ploidy Verification

Abstract The modified preparation technique developed in the present study has provided an excellent chro- mosome metaphase spread from the whole body of larvae of the red hybrid tilapia Oreochromis mossambicus (Peters, 1852) X Oreochromis niloticus (Linnaeus, 1758). Unlike other chromosome preparation methods, this modified technique showed a reduction in cell loss while suspending cells during the dropping process. This modified technique can therefore be widely applied not only to various tilapias but also to other teleostean fishes for preparing chromosome spreads. The best treatment parameters for preparing good chromosome spreads from red hybrid tilapia were optimized as 0.01% concentration of colchicine for 4-6 hours, hypotonic 40 min- utes treatment, fixation with carnoy solution at 3:1 ratio and a concentration of 10% Giemsa for 20 minutes.

The Promise of Human Induced Pluripotent Stem Cells in Dental Research

Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC lines in vitro from patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.

A study on the energy source in the developing embryo of the mangrove horseshoe crab, Carcinoscorpius rotundicauda (Latreille)

The mangrove horseshoe crab, Carcinoscorpius rotundicauda, is an Asian species found in Malaysia. This ancient arthropod has a long incubational period during which it depends on various energy sources for both embryogenesis and organogenesis. This study describes the trend of energy utilization from the endogenous reserves by the developing embryos from 0 to 40 days of incubation (until the hatching of the larvae). The dry weight, insoluble protein, carbohydrate, glycogen and lipid showed a declining trend from 0 to 40 days of incubation, whereas the wet weight, water content, ash content and soluble protein showed an increasing trend. Selected micro-elements such as Cu2+, Fe2+ and Zn2+ also demonstrated an interesting trend in the developing eggs when the egg mass was subjected to inductively coupled plasma mass spectrometry analysis, where these elements showed a high correlation with the moulting stages and egg development. Maximum variations within the micro-elements were observed during the 1st (10 days after fertilization) and 2nd (35–36 days after fertilization) moulting stages within the developing eggs. This study clearly indicated that the moulting cycles of C. rotundicauda during embryonic development influence energy utilization in the form of carbohydrates, lipids, proteins, glycogen and other micro-elements.

Triploidy induction by heat-shock treatment in red tilapia

The possible use of sterile triploid red tilapia is an interesting option for culture due to their proliferating breeding activities. The aim of the present study was to investigate and optimize the time of heat-shock treatment to prevent second polar body extrusion from the newly fertilized eggs of red tilapia, to produce a maximum number of triploid individuals. Heat-shock treatment was applied at a temperature of 41°C for a total duration of 3.5 minutes after 2, 3, 4, 4.5, 5 and 6 minutes of fertilization. The best survival rate (67.0%) and triploid percentage (89.7%) was observed for the treatment at 4 minutes after fertilization. It is thus successfully demonstrated that 4 minutes after fertilization was the most suitable timing of heat-shock treatment for second polar body retention in newly fertilized eggs of red tilapia.

Homeobox genes and tooth development: Understanding the biological pathways and applications in regenerative dental science

OBJECTIVES Homeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master regulator for developmental genes, which involves coordinated actions of various auto and cross-regulatory mechanisms. In this review, we summarize the expression pattern of homeobox genes in relation to the tooth development and various signaling pathways or molecules contributing to the specific actions of these genes in the regulation of odontogenesis. MATERIALS AND METHODS An electronic search was undertaken using combination of keywords e.g. Homeobox genes, tooth development, dental diseases, stem cells, induced pluripotent stem cells, gene control region was used as search terms in PubMed and Web of Science and relevant full text articles and abstract were retrieved that were written in English. A manual hand search in text books were also carried out. Articles related to homeobox genes in dentistry and tissue engineering and regenerative medicine of odontogenesis were selected. RESULTS The possible perspective of stem cells technology in odontogenesis and subsequent analysis of gene correction pertaining to dental disorders through the possibility of induced pluripotent stem cells technology is also inferred. CONCLUSIONS We demonstrate the promising role of tissue engineering and regenerative medicine on odontogenesis, which can generate a new ray of hope in the field of dental science.

Growth Performance of Triploid Red Tilapia Reared Under Laboratory Conditions

Triploidy could reduce breeding activity in tilapia without the use of hormones. In this study, the effect of triploidy on survival, growth, and gender of a line of red hybrid tilapia (Oreochromis mossambicus X Oreochromis niloticus) was assessed relative to the performance of diploid siblings. Triploidy was induced by preventing second polar body extrusion by applying either heat or cold shock. Growth was similar for both ploidies during the first 90 days of culture. However, at the age of 120 days, the average body weight of triploids produced by heat shock (215.5 ± 3.61 g) was significantly higher than that of cold shock (192.7 ± 2.6 g) and the diploid control (191.9 ± 1.74 g). Survival among triploids was inferior to diploids. Percentage of males in the triploid population was 82.9% in the heat-shocked treatment group, 54.8% in the cold-shock treatment, and 50% in the diploid control. Maximum attainable weight of red tilapia was calculated by applying the Ford-Walford growth plot: 650 g (heat-shocked triploids), 490 g (cold-shocked triploids), and 440 g in the diploid control.

Stem Cells in Dentistry: Potential Applications and Perspectives in Clinical Research

Over the past decade there has been a dramatic progress in the field of stem cell research and a rapid surge in investigation of stem cell therapies. Current clinical trials using a variety of stem cell types are addressing a wide spectrum of conditions. Among different types of adult stem cells discovered, dental stem cells are among the newest found in the MSC repertoire. Dental stem cells can be isolated relatively easily through minimally invasive procedures from both young and adult populations. In particular, dental pulp stem cells (DPSCs) are found to have outstanding potentials because of their superior proliferation, multi-potent differentiation, regeneration, immunoprivileged, and immunomodulatory properties. In addition, DPSCs can be reprogrammed into induced pluripotent stem cells (iPSCs) with high efficiency, possibly due to their dual meso-ectodermal origin and intrinsic expression of pluripotent factors. The current chapter discusses their origin, biological niche, functional properties, reprogramming capability, and application potentials for therapeutics, cell banking, and tissue engineering toward construction of both dental and non-dental tissues. This chapter consists of three main sections: (1) Developmental biology and organization of dental-related stem cells; (2) Dental stem cell properties for cell-based therapeutics; (3) Potentials of dental stem cells for tissue engineering and cell banking. Overall this review provides current biological knowledge on dental stem cells and their translational applications at both in vitro and in vivo levels. The chapter is designed for both clinicians and researchers involved in odontogenesis and stem cell research alike.