Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

Injury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium in in vivo animal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials

Expression Profiles of Wnt Genes during Neural Differentiation of Mouse Embryonic Stem Cells

The Wnt family of secreted signaling proteins regulates many aspects of animal development and the behavior of several types of stem cells, including embryonic stem (ES) cells. Activation of canonical Wnt signaling has been shown to either inhibit or promote the differentiation of ES cells into neurons, depending on the stage of differentiation. Here, we describe the expression of all 19 mouse Wnt genes during this process. Using the well-established retinoic acid induction protocol we found that all Wnt genes except Wnt8b are expressed as ES cells differentiate into neurons, many of them in dynamic patterns. The expression pattern of 12 Wnt genes was analyzed quantitatively at 2-day intervals throughout neural differentiation, showing that multiple Wnt genes are expressed at each stage. A large proportion of these, including both canonical and noncanonical Wnts, are expressed at highest levels during later stages of differentiation. The complexity of the patterns observed indicates that disentangling specific roles for individual Wnt genes in the differentiation process will be a significant challenge

An overview of in vitro research models for Alzheimer`s disease (AD)

Alzheimer’s disease (AD) is the most common form of age-related dementia. It is a neurodegenerative disease characterized by two aberrant features, the amyloid plaques and the neurofibrillary tangles which result in progressive memory loss and cognitive disturbances. This has led to devastating suffering to the patient, caregivers, family and economy of the country. As a result, scientists are putting efforts in understanding the mechanisms underlying the development of the disease as well as treatment for the disease. To do so, an ideal model is required that can mimic the development of AD,demonstrating the progressive degeneration of the neurons and formation of amyloid plaques and neurofibrillary tangles. In this review paper, currently available in vitro models for AD will be disc ussed, which include the cancer, primary culture and stem cell lines, highlighting on the benefits and limitations of each. More attention will be focused on the latest established disease-specific induced pluripotent stem cells (iPSCs)isolated from familial AD patients and Dow n syndrome patients. These models have their own advantages and limitations, therefore, more research needs to be done to come up with a model that is suitable not only for fundamental understanding of the disease but also for drug discovery and development

A plethora of human pluripotent stem cells

At the early stages of mammalian development, a number of developmentally plastic cells appear that possess the ability to give rise to all of the differentiated cell types normally derived from the three primary germ layers - unique character known as pluripotency. To date, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to be truly pluripotent. However, recent studies have revealed a variety of other cells that demonstrate pluripotentiality, including very small embryonic-like stem cells (VSELs), amniotic fluid stem cells (AFSCs), marrow-isolated adult multilineage inducible cells (MIAMI) and multipotent adult precursor cells (MAPCs). This review summarises key features of these six kinds of pluripotent and potentially pluripotent stem cells (ESCs, iPSCs, VSELs, AFSCs, MIAMI and MAPCs) and the evidence for their pluripotency properties

Evaluation of two cell culture media in culturing rat full term amniotic fluid cells

Introduction: Amniotic fluid (AF) consists of heterogenous population of cells with high diagnostic and therapeutic values. The study of rat amniotic fluid cells is very limited, despite the extensive use of this animal model in biomedical research. Primary culture of rat AF cells, especially from full term pregnancies has not been well established. Here we attempt to determine the suitable medium in culturing rat AF cells that would enhance the cell viability, growth rate and heterogeneity. Methods: The cell viability, growth rate and heterogeneity of rat AF cells were compared upon culturing the primary cells in two different media; Amniomax or RPMI. Cell viability study was carried out using trypan blue staining, while the growth rate was monitored based on the time required to passage the cells (population doubling time in hour). The heterogeneity of cells was examined based on the morphology of the cells. Statistical analysis was performed using t-test. Results: Amniomax was observed to provide a better culture condition in culturing rat AF cells as the cells are more viable, grow faster and more heterogenous as compared to the cells grown in RPMI. Conclusion: Amniomax is a more suitable medium for high quality and viability of full term rat AF cell culture, as compared to RPMI. Thus, warranting propagation of more rat AF cells for biomedical research

Narrative problem-based learning in biomedical sciences

Problem-based learning (PBL) is a process of acquiring knowledge based on the problem given. This method will give understanding on the underlying problem. PBL improves teaching practices by replacing traditional teaching methods. It reduces the passive information giving process thus making undergraduate education a platform for life¬long learning. PBL reverses the traditional approach to teaching and learning. Problem based learning is a method of teaching and learning where the students need to be proactive in their discussion. Case studies were given and students were required to explore from all aspect of Biomedical Science to help them to understand the situation underlying it. Narrative Problem-based Learning was based on non_ction events. It was taken from the experience of those who underwent the events. Triggers presented in each topic were aimed to help final year Biomedical students to integrate knowledge gained throughout their study in the field of Biomedical Sciences

Activin A: its role and involvement in inflammatory diseases

Activin proteins are members of the transforming growth factor-β family. Activin A is involved in several biological responses including wound repair, cell death, proliferation and differentiation of many cell types. Biologically active activins consist of homodimers or heterodimers of two beta (β) subunits that are linked together by a single covalent disulphide bond. The subunits in humans are βA, βB, βC and βE. As an example, a combination of two βA subunits will produce a unit of activin A. These proteins are found in most cells of body such as macrophage and activated circulating monocytes. Their role in inflammation can be categorised into two types, either pro- or anti-inflammatory agents, depending on the cell type and phase. Activin signals are kept in balance by antagonist follistatin (Fst), which is a glycoprotein expressed in tissues and encoded by the follistatin gene in humans

Receptor for advanced glycation end products and its involvement in inflammatory diseases

The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF- B as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions

Mesenchymal stem cells: from stem cells to sarcomas

Mesenchymal stem cells (MSCs) have garnered vast interests in clinical settings, especially in regenerative medicine due to their unique properties—they are reliably isolated and expanded from various tissue sources; they are able to differentiate into mesodermal tissues such as bones, cartilages, adipose tissues, and muscles; and they have unique immunosuppressive properties. However, there are some concerns pertaining to the role of MSCs in the human body. On one hand, they are crucial component in the regeneration and repair of the human body. On the contrary, they are shown to transform into sarcomas. Although the exact mechanisms are still unknown, many new leads have pointed to the belief that MSCs do play a role in sarcomagenesis. This review focuses on the current updates and findings of the role of MSCs in their transformation process into sarcomas