Present Status of Research on the Regenerative Potential of Dental Pulp Stem Cells in Malaysia: A Systematic Review

Stem cells from human exfoliated deciduous teeth (SHED) or dental pulp stem cells (DPSCs) from permanent teeth are considered promising sources of mesenchymal stem cells. It requires a less invasive technique to isolate stem cells from exfoliated or permanent teeth. Hence this study aimed to identify the present status of research on the regenerative potential of SHED/DPSCs in Malaysia. The results indicate that only 60 articles were published in regenerative medicine from Malaysia till 5th July 2019. Only 16 tertiary institutes and four industries/clinics were involved in these studies. A poor pattern of collaboration has also been identified. Outcomes of this study have emphasized the conduction of more research on the regenerative potential of SHED/DPSCs, and active collaboration among the tertiary institutes and industries for successful translation of these cells from bench side to bedside.

Induced pluripotent stem cells are Japanese brand sources for therapeutic cells to pretrial clinical research

iPSCs are promising and have potential benefits for medical use, understanding human organogenesis, and cell therapy for advanced diseases. iPSCs are derived pluripotent cells which can further differentiate into functional human cell-lineages, such as neuronal, epithelial cells, cardiac cell, immune cell, and blood cells, etc. Thirteen years on, the discovery of iPSC has revolutionized the field of regenerative medicine, and also the number of clinical studies using iPSC has been growing rapidly worldwide. However, Japan is leading the race of iPSC-based studies and clinical trials due to government support. The Japanese government implemented the world’s fastest approval system and set to host first pretrial clinical studies using iPSC derived therapeutic products. Also, multinational companies of Japan are investing enormously in iPSC-based research for mobilization of iPSC-derived regenerative products to the research institution globally. This review presents an overview of iPSCs, potential benefits, commercialization of iPSC, iPSC-based pretrial clinical studies, and iPSC biobanking in Japan.

Ovarian cancer cells with CD133+ phenotype is more resistant against Ngai Bun Boesenbergia pandurata extract than original ovarian cancer cells

Introduction: Ovarian cancer is one of the most common cancers in women. Due to the difficulty in early detection and treatment of ovarian cancer, many research studies and clinical trials have been developed to discover more efficient therapies. Besides Western medicine, traditional medicine has gained increased interest as a research field with potential to lead to the production of marketable therapeutic products. With the diversity of tropical plants in Asia, traditional medicine has been very popular and has served as a traditional therapy for generations. The Ngai bun (Boesenbergia pandurata) root is used not only as a food spice but also in ethnomedicine. This study aimed to compare the anti-tumor activity of Boesenbergia pandurata root extract against ovarian cancer cells and CD133+ ovarian cancer cells that were enriched from the original ovarian cancer cells. Methods: Crude extract of Boesenbergia pandurata roots were prepared in two kinds of solvents (methanol and chloroform). The ovarian cancer cells OVP-10 were used in this study. The population of CD133+ ovarian cancer cells (CD133+OVP-10) were sorted from the OVP-10 cancer cells. Both OVP-10 cells and CD133+OVP-10 cells were treated with these crude extracts. Adiposederived stem cells (ADSCs) were used as control normal cells for all assays. The anti-tumor activity of extracts were evaluated based on the IC50 values. Results: Based on the IC50 index, the chloroform extract had an anti-tumor activity higher than that of methanol extract, on both OVP-10 and CD133+OPV-10 cells (IC50 of methanol and chloroform extracts were 330.1 +/- 16.9 ug/mL and 246.5 +/- 21.2 ug/mL, respectively, for OVP-10 cells; IC50 of methanol and chloroform extracts were 411.8 +/- 83.7 ug/mL and 307 +/- 9.2 ug/mL respectively, for CD133+OVP-10 cells). The results also showed that CD133+OVP-10 cells were more resistant to chloroform extract than were OVP-10 cells (307 +/- 9.2 mg/mL vs. 246.5 +/- 21.2 mg/mL, respectively, for CD133+OVP-10 vs. OVP-10 cells, p < 0.05). Conclusion: The chloroform extract of Boesenbergia pandurata roots displayed strong antitumor activity against ovarian cancer cells OVP-10 and CD133+OVP-10; the latter cells were found to be more resistant than the original ovarian cancer cells.

Isolation of cancer stem-like cells from hepatocellular carcinoma cell line HepG2 by methods of magnetic-activated cell sorting, spheroid culture, and anti-tumor drug-resistant selection: A primary evaluation

Introduction: Recently reported data have suggested that only a small subset of cancer cells possess the capability to initiate malignancies. These observations were based on investigation of cells within the primary tumors displaying a distinct surface marker pattern. CD133 marker is a putative hematopoietic and neuronal stem cell marker, which is also considered to be a tumorigenic marker in brain, prostate and liver. Recent studies have shown that a small population of CD133-positive cells, indeed, exists in human hepatocellular carcinoma (HCC) cell lines and primary HCC tissues. This study was aimed at isolating the cancer stem-like cells from hepatocellular carcinoma cell line HepG2 using three different methods: magnetic-activated cell sorting (MACS), spheroid culture (SC), and anti-tumor drug (ATD) resistant selection. Methods: HepG2 hepatocellular carcinoma cells were expanded to yield enough cells that could be used to isolate cancer stem-like cells by these three methods. For MACS, cancer stem-like cells were sorted using anti-CD133 monoclonal antibody. For the second method, cancer stem-like cells were enriched by selection of anti-tumor drug resistance property. Lastly, for the third method, three-dimensional (3D) culture was used to enrich for the cancer stem-like cells. The cells obtained by the three methods were expanded to obtain an adequate number of cells for confirmation of CD133 expression. Results: The expression of CD133+ cells in the three methods was found to be different. In the MACS method, the expanded CD133+ sorted cells cultured through 2 passages only contained 0.40 % CD133+ cells. In the 3D spheroid cell culture, of the population of cells there were 38.39 % that were CD133+ cells. Lastly, in the anti-tumor drug (doxorubicin at 150 nM) resistant selection, 66.22 % were CD133+ cells. Conclusion: This study shows that isolation of HepG2 derived CD133+ population by culture with doxorubicin (150 nM) yields the highest efficiency and purity of the 3 methods studied.

Therapeutic role of bone marrow-derived stem cells and zinc sulfate for reduction of liver fibrosis

Introduction: Hepatic fibrosis is considered as the initial state of any chronic hepatic disease; progression causes accumulation of extracellular matrix (ECM) and develops into cirrhosis. In case of liver failure, transplantation was considered as the only suitable therapy but due to the hurdles in transplantation, therapy using stem cells was promoted. Mesenchymal stem cells (MSCs) are widely used for the treatment of a variety of diseases. Oxidative stress at the damage site causes poor MSC proliferation and engraftment. Thus, it is necessary to induce antioxidants with MSCs to enhance potency. Methods: To explore the therapeutic potential of zinc sulfate (ZnSO4) and MSCs on carbon tetra chloride (CCl4)-induced hepatic toxicity, 6-8 week-old female albino mice (BALB/c) were used. Initially, mice were infected with CCl4 and then intra-peritoneally injected with MSCs only, ZnSO4 only, or a combination of MSCs and ZnSO4. MSCs were isolated from femur and tibia of mice, and were cultured under control conditions. Results: The morphological results revealed that in contrast to MSC-only therapy, ZnSO4 enhanced the therapeutic potential of MSCs when administered to CCl4-injured mice. Biochemically, level of serum Alanine Transaminase (ALT) and total bilirubin was found to be significantly decreased in ZnSO4 + MSC transplanted mice. Histopathological examination also revealed that ZnSO4 + MSC transplantation induced a strong anti-apoptotic effect on CCl4-injured liver. Reverse transcription polymerase chain reaction (RT-PCR) detected a noteworthy anti-fibrotic effect of MSCs in the presence of ZnSO4, down-regulation of apoptotic marker (Bax), and up-regulation of anti-apoptotic (Bcl-xl) and hepatic (Albumin) markers. Conclusion: Thus, it was concluded that the presence of ZnSO4 reduced oxidative stress, enhanced the proliferation rate of MSCs, and significantly attenuated hepatic fibrosis.

Mesenchymal stem cells transplantation reduces diabetic nephropathy

Diabetes mellitus is a metabolic disease in which the pancreas is unable to produce enough insulin due to the destruction of b -cells or the body does not utilize insulin properly. Continuous fluctuation of blood glucose levels is responsible for prolonged complications such as diabetic nephropathy (DN), diabetic retinopathy, or diabetic cardiomyopathy. Approximately, 20-30% of all diabetic patients face DN, which causes the formation of diabetic glomerular lesions and reduced glomerular filtration rate. In the case of renal failure, kidney transplantation is the only available therapy, however, it is expensive and almost unattainable due to unavailability of donors and host immune rejection. Stem cells are an alternative and attractive source of therapy because of their proliferative nature and the ability to produce distinct specialized cells. Mesenchymal stem cells (MSCs), which are derived from bone marrow, possess an anti-inflammatory property and the ability of selfrenewal and differentiation into a variety of specialized cells. MSCs are widely used to treat different diseases including DN and they have shown encouraging outcomes. This review provides details about the regenerative efficiency of using MSCs in treating diabetic nephropathy.

Expression of CD34 marker in the adipose tissue derived stem cells

Introduction: Adipose-derived stem cells (ADSCs) are considered as mesenchymal stem cells (MSCs). Indeed, they display all characteristics of MSCs that compliant with the minimal criteria of MSCs suggested by Domonici et al. (2006). However, some recent studies showed that ADSCs contain the subpopulation that was positive with CD34 marker – a marker of hematopoietic stem cells. This study aimed to analyze and determine the expression of CD34 marker in ten samples of ADSCs obtained from 10 donors. Methods: All ADSC samples were isolated and expanded according to the published previous protocols. They were confirmed as the MSCs with some markers and differentiation potential, excepting the CD34 expression. Then they were cultured and analyzed the expression of CD34 by flow cytometry at passage 3, 5, 7 and 9. Results: The results showed that expression of CD34 in ADSCs was different between donors and their passages that accounted from 1.21% to 23.38%. Conclusion: These results suggested that ADSCs are not ‘truly” MSCs like MSCs from bone marrow.

An evolution of stem cell research and therapy in Viet Nam

Stem cell research and therapy are one of the most attractive studies in the biomedicine. Not only in the bench, nowadays stem cells but also become the bustling industry. In Vietnam, biomedical scientists started to study and apply stem cells since 1995. From that, Vietnamese scientists got some significant achievements in stem cell research and therapy, especially in stem cell therapy for disease treatment. This report aimed to provide an overview of stem cell research and therapy from 1995 to date. Stem cell research activities were collected and analyzed based on the publications, projects about stem cells in some databases including Web of Science, Google Scholar, Embase, and national scientific information. The results showed that stem cell research and therapy significantly increased from 2009 to date with more publications about stem cells and more clinical applications. With this growth rate, we hope that Vietnam can develop the stem cell industry and become one the stem cell center in the Asian and the world.

Expanded mesenchymal stem cell transplantation is safe in both local injection and vein transfusion

More than 500 clinical trials are using mesenchymal stem cells (MSCs) in the world to treat some different diseases. The safety of expanded MSC transplantation is the most important thing to ensure that this therapy can become the routine treatment for human diseases. More than five MSCs based stem cell drug products are approved at various countries demonstrated that expanded MSCs are safe in both local injection and transfusion. Moreover, some recent reports for 5 and 10 years followed-up clinical trials using expanded MSCs confirmed that there is not different tumorigenesis between the patients with and without expanded MSC transplantation. This letter aims to provide some evidences about the safety of expanded MSCs in clinical applications. However, the MSC quality should be stritcly controlled during the in vitro MSC expansion.