Cellular immortality happens upon impairment of cell-cycle checkpoint pathways (p53/p16/pRb), reactivation or up-regulation of telomerase enzyme, or upregulation of some oncogenes or oncoproteins leading to a higher rate of cell division.There are also some other factors and mechanisms involved in immortalisation, which need to be discovered. Immortalisation of cells derived from different sources and establishment of immortal cell lines has proven useful in understanding the molecular pathways governing cell developmental cascades in eukaryotic, especially human, cells. After the breakthrough of achieving the immortal cells and understanding their critical importance in the field of molecular biology, intense efforts have been dedicated to establish cell lines useful for elucidating the functions of telomerase, developmental lineage of progenitors, self-renewal potency, cellular transformation, differentiation patterns and some bioprocesses, like odontogenesis. Meanwhile, discovering the exact mechanisms of immortality, a major challenge for science yet, is believed to open new gateways toward understanding and treatment of cancer in the long term. This review summarises the methods involved in establishing immortality, its advantages and the challenges still being faced in this field.
Regenerative medicine is a new and promising mode of therapy for patients who have limited or no other options for the treatment of their illness. Due to their pleotropic therapeutic potential through the inhibition of inflammation or apoptosis, cell recruitment, stimulation of angiogenesis, and differentiation, stem cells present a novel and effective approach to several challenging human diseases. In recent years, encouraging findings in preclinical studies have paved the way for many clinical trials using stem cells for the treatment of various diseases. The translation of these new therapeutic products from the laboratory to the market is conducted under highly defined regulations and directives provided by competent regulatory authorities. This review seeks to familiarize the reader with the process of translation from an idea to clinical practice, in the context of stem cell products. We address some required guidelines for clinical trial approval, including regulations and directives presented by the Food and Drug Administration (FDA) of the United States, as well as those of the European Medicine Agency (EMA). Moreover, we review, summarize, and discuss regenerative medicine clinical trial studies registered on the Clinicaltrials.gov website.
ECM components include a number of osteoinductive and osteoconductive factors, which are involved in bone fracture healing. In this study, a combination of adipose derived mesenchymal stem cells (Ad-MSCs), cancellous bone graft (CBG), and chitosan hydrogel (CHI) was applied to the non-union bone fracture and healing effects were evaluated for the first time. After creation of animal models with non-union fracture in rats, they were randomly classified into seven groups. Radiography at 0, 2, 4, and 8 weeks after surgery, indicated the positive effects of Ad-MSCs + CBG + CHI and Ad-MSCs + CBG in treatment of bone fractures as early as 2 weeks after the surgery. These data were confirmed with both biomechanical and histological studies. Gene expression analyses of Vegf and Bmp2 showed a positive effect of Ad-MSCs on vascularization and osteogenic differentiation in all groups receiving Ad-MSCs, as shown by real-time PCR. Immunofluorescence analysis and RT-PCR results indicated existence of human Ad-MSCs in the fractured region 8 weeks post-surgery. In conclusion, we suggest that application of Ad-MSCs, CBG, and CHI, could be a suitable combination for osteoinduction and osteoconduction to improve non-union bone fracture healing. Further investigations are required to determine the exact mechanisms involved in this process before moving to clinical studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018.
Stem cell therapy in recent years has gained much attention as the modern therapeutic approach to treat diseases. Mesenchymal stem cells (MSCs) are seen as the most reliable cells applied in therapy over other stem cells because of their versatility. Bone and cartilage diseases (osteo-diseases) are the major target of therapy using MSCs. In this perspective, we have statistically analyzed the data available on clinical trials registry databases regarding the mesenchymal stem cell based therapy for a number of mentioned diseases and paid attention towards the osteodiseases. We report that MSC therapy for osteo-diseases needs optimization in its standards to achieve acceptable results so that we can apply it in daily routine clinical practice.
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