Recent Emerging Trend in Stem Cell Therapy Risk Factors.

Different types of stem cells have remarkable characteristics such as high proliferation rate, multi/pluripotency, self-renewal, and broad differentiation that can effectively treat diseases, cancers, and damage. Despite abundant therapeutic applications of stem cells in medical science, numerous risks threaten stem cell transplantation. Tumor development, immune response, cellular senescence, dosage effects, and administration timing are critical risks that should be considered in stem cell therapy. Hence, an investigation of possible risks is required before utilizing stem cell-based medicinal products in the clinical phase and human trials. This review aims to survey the literature and perspectives on the advantages and risks associated with pluripotent and multipotent stem cells.

Cell-based Therapy for Ocular Disorders: A Promising Frontier.

As the ocular disorders causing the long-term blindness or optical abnormalities of the ocular tissue entirely affect life quality, an insight into their corresponding pathogenesis and the expansion of attitudes authorizing earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for hindrance of development of visual impairment to blindness. Accordingly, stem cells because of their particular competencies have attracted pronounced attention to be applied in regenerative medicine of ocular diseases. In the last decades, a wide spectrum of stem cells surrounding Mesenchymal Stem/Stromal Cells (MSC), Neural Stem Cells (NSCs), and embryonic/induced pluripotent stem cells (ESCs/iPSCs) accompanied by Müller glia, ciliary epithelia-derived stem cells, and Retinal Pigment Epithelial (RPE) stem cells have been widely investigated to report their safety and efficacy in preclinical models and also human subjects. In this regard and the first interventions, RPE cell suspensions were successfully utilized to ameliorate visual defects of the patients suffering from Age-related Macular Degeneration (AMD) after subretinal transplantation. Herein, we will explain the pathogenesis of ocular diseases and highlight the novel discoveries and recent findings in the context of stem cell-based therapies in these disorders, focusing on the last decade's in vivo reports.

Umbilical Cord Mesenchymal Stem/Stromal Cells Potential to Treat Organ Disorders; An Emerging Strategy.

Currently, Mesenchymal Stem/Stromal Cells (MSCs) have attracted growing attention in the context of cell-based therapy in regenerative medicine. Following the first successful procurement of human MSCs from Bone Marrow (BM), these cells isolation has been conducted from various origins, in particular, the Umbilical Cord (UC). Umbilical Cord-Derived Mesenchymal Stem/Stromal Cells (UC-MSCs) can be acquired by a non-invasive plan and simply cultured, and thereby signifies their superiority over MSCs derived from other sources for medical purposes. Due to their unique attributes, including self-renewal, multipotency, and accessibility concomitant with their immunosuppressive competence and lower ethical concerns, UC-MSCs therapy is described as encouraging therapeutic options in cell-based therapies. Regardless of their unique aptitude to adjust inflammatory response during tissue recovery and delivering solid milieu for tissue restoration, UC-MSCs can be differentiated into a diverse spectrum of adult cells (e.g., osteoblast, chondrocyte, type II alveolar, hepatocyte, and cardiomyocyte). Interestingly, they demonstrate a prolonged survival and longer telomeres compared with MSCs derived from other sources, suggesting that UC-MSCs are desired source to use in regenerative medicine. In the present review, we deliver a brief review of UC-MSCs isolation, expansion concomitantly with immunosuppressive activities, and try to collect and discuss recent pre-clinical and clinical researches based on the use of UC-MSCs in regenerative medicine, focusing on with special focus on in vivo researches.

Stem cell in neurodegenerative disorders; an emerging strategy.

Neurodegenerative disorders are a diversity of disorders, surrounding Alzheimer's (AD), Parkinson's (PD), Huntington's diseases (HD), and amyotrophic lateral sclerosis (ALS) accompanied by some other less common diseases generally characterized by either developed deterioration of central or peripheral nervous system structurally or functionally. Today, with the viewpoint of an increasingly aging society, the number of patients with neurodegenerative diseases and sociomedical burdens will spread intensely. During the last decade, stem cell technology has attracted great attention for treating neurodegenerative diseases worldwide because of its unique attributes. As acknowledged, there are several categories of stem cells being able to proliferate and differentiate into various cellular lineages, highlighting their significance in the context of regenerative medicine. In preclinical models, stem cell therapy using mesenchymal stem/stromal cells (MSCs), hematopoietic stem cells (HSCs), and neural progenitor or stem cells (NPCs or NSCs) along with pluripotent stem cells (PSCs)-derived neuronal cells could elicit desired therapeutic effects, enabling functional deficit rescue partially. Regardless of the noteworthy progress in our scientific awareness and understanding of stem cell biology, there still exist various challenges to defeat. In the present review, we provide a summary of the therapeutic potential of stem cells and discuss the current status and prospect of stem cell strategy in neurodegenerative diseases, in particular, AD, PD, ALS, and HD.

Effects of Hypoxia on Biology of Human Leukemia T-cell Line (MOLT-4 cells) Co-cultured with Bone Marrow Mesenchymal Stem Cells.

BACKGROUND: One of the most significant problems in the treatment of leukemia is the expansion of resistance to chemotherapeutic agents. Therefore, assessing the drug resistance and especially the drug resistance genes of leukemic cells is important in any treatment. The impact of Mesenchymal Stem Cells (MSCs) and hypoxic condition have been observed in the biological performance of majority of leukemic cells. METHODS: MOLT-4 cells were co-cultured with MSCs in the hypoxic condition induced by Cobalt Chloride (CoCl2) for 6 and 24 hr. Then, apoptosis of cells was analyzed using annexin-V/PI staining and expression of the drug resistance genes including MDR1, MRP, and BCRP along with apoptotic and anti-apoptotic genes, including BAX and BCL2, was evaluated by real-time PCR. RESULTS: The hypoxic condition for MOLT-4 cells co-cultured with MSCs could significantly increase the expression of MDR1 and BCRP genes (p<0.05) which are involved in drug resistance. Also, the results indicated that this condition significantly increases the expression of BCL2 (p<0.05) and reduces the apoptosis in MOLT-4 cells co-cultured with MSCs in the hypoxic condition. CONCLUSION: These effects can demonstrate the important role of hypoxia and MSCs on the biological behavior of Acute Lymphoblastic Leukemia (ALL) cells that may lead to particular treatment outcomes.

Promoter Methylation Status of Survival-Related Genes in MOLT- 4 Cells Co-Cultured with Bone Marrow Mesenchymal Stem Cells under Hypoxic Conditions.

OBJECTIVES: DNA methylation is a well-studied epigenetic mechanism that is a potent arm of the gene expression controlling machinery. Since the hypoxic situation and the various cells of bone marrow microenvironment, e.g. mesenchymal stem cells, play a role in the in vivo and in vitro biology of leukemic cells, we decided to study the effects of hypoxia and mesenchymal stem cells (MSCs) on the promoter methylation pattern of BAX and BCL2 genes. MATERIALS AND METHODS: In this experimental study, the co-culture of MOLT-4 cells with MSCs and treatment with CoCl2 was done during 6, 12, and 24 hour periods. Total DNA was extracted using commercial DNA extraction kits, and sodium bisulfite (SBS) treatment was performed on the extracted DNA. Methylation specific polymerase chain reaction (MSP) was used to evaluate the methylation status of the selected genes' promoter regions. RESULTS: The BAX and BCL2 promoters of untreated MOLT-4 cells were in partial methylated and fully unmethylated states, respectively. After incubating the cancer cells with CoCl2 and MSCs, the MSP results after 6, 12, and 24 hours were the same as untreated MOLT-4 cells. In other words, the exposure of MOLT-4 cells to the hypoxia-mimicry agent and MSCs in various modes and different time frames showed that these factors have exerted no change on the methylation signature of the studied fragments from the promoter region of the mentioned genes. CONCLUSIONS: Hypoxia and MSCs actually have no notable effect on the methylation status of the promoters of BAX and BCL2 in the specifically studied regions. DNA methylation is probably not the main process by which MSCs and CoCl2 induced hypoxia regulate the expression of these genes. Finally, we are still far from discovering the exact functional mechanisms of gene expression directors, but these investigations can provide new insights into this field for upcoming studies.