Therapeutic potential of adult stem cells

The aim of cell-based therapies is to replace or repair damaged tissues and organs. A diverse number of disorders are amenable to this approach, including haematopoietic, neurological and cardiovascular diseases, as well as bone defects and diabetes. Central to the success of cell therapy is the necessity to be able to identify, select, expand and manipulate cells outside the body. Recent advances in adult stem cell technologies and basic biology have accelerated therapeutic opportunities aimed at eventual clinical applications. Adult stem cells with the ability to differentiate down multiple lineages are an attractive alternative to human embryonic stem cells (hES) in regenerative medicine. In many countries, present legislation surrounding hES cells makes their use problematic, and indeed the origin of hES cells may represent a controversial issue for many communities. However, adult stem cells are not subject to these issues. This review will therefore focus on adult stem cells. Based on their extensive differentiation potential and, in some cases, the relative ease of their isolation, adult stem cells are appropriate for clinical development. Recently, several observations suggest that multipotential adult stem cells are capable of producing a whole spectrum of cell types, regardless of whether or not these tissues are derived from same germ layer; highlighting the opportunity to manipulate stem cells for therapeutic use.     

Adult human mesenchymal stem cell as a target for neoplastic transformation

The neoplastic process may involve a cancer stem cell. This concept has emerged largely from the careful analysis of tumour biopsy systems from haematological, breast and brain tumours. However, the experimental systems necessary to provide the cellular and molecular evidence to support this important concept have been lacking. We have used adult mesenchymal stem cells (hMSC) transduced with the telomerase hTERT gene to investigate the neoplastic potential of adult stem cells. The hTERT-transduced line, hMSC-TERT20 at population doubling level (PDL) 256 showed loss of contact inhibition, anchorage independence and formed tumours in 10/10 mice. hMSC-TERT4 showed loss of contact inhibition at PDL 95, but did not exhibit anchorage independence and did not form tumours in mice. Both lines had a normal karyotype but showed deletion of the Ink4a/ARF locus. At later passage, hMSC-TERT4 also acquired an activating mutation in KRAS. In hMSC-TERT20, expression of the cell cycle-associated gene, DBCCR1 was lost due to promoter hypermethylation. This epigenetic event correlated with acquisition of tumorigenicity. These data suggest that the adult hMSCs can be targets for neoplastic transformation and have implications for the development of novel anticancer therapeutics and for the use of hMSC in tissue engineering and transplantation protocols.     

Evaluation of retinal nerve fiber layer thickness in vernal keratoconjunctivitis patients under long-term topical corticosteroid therapy

Purpose: The aim of this study was to evaluate the retinal nerve fiber layer (RNFL) thickness in vernal keratoconjunctivitis (VKC) patients who were under long-term topical corticosteroid therapy.

Methods: Thirty-six eyes of 36 VKC patients with clear cornea and normal videokeratography and 40 eyes of 40 age- and gender-matched normal children were included in the study. Clinical and demographic characteristics of the patients were noted and detailed ophthalmological examination was performed. Visual acuity (VA), spherical equivalent (SE), axial length (AL) and RNFL thickness measurements were compared between the groups. To correct ocular magnification effect on RNFL, we used Littmann’s formula.

Results: All VKC patients had history of topical corticosteroid use and the mean duration of the topical corticosteroid use was 23.8?±?9.09 months. There was no significant difference between the groups in terms of intraocular pressure (IOP). VKC group had significantly worse VA, greater SE and AL and thinner mean global, superior and inferior RNFL thickness. There were significant negative correlations between the duration of topical corticosteroid use and the mean global, superior and temporal RNFL thickness in VKC group. After correction of magnification effect, VKC group still had thinner mean global, superior and inferior RNFL thickness, and significant difference between the groups in inferior RNFL thickness did not disappear.

Conclusion: Significant RNFL thickness difference between the groups suggests a possible effect of long-term corticosteroid use in VKC patients. Because visual field (VF) analysis in pediatric patients is difficult to perform and IOP may be illusive, RNFL thickness measurements in addition to routine examinations in VKC patients may help clinicians in their practice.     

Investigation of the effects of the toll-like receptor 4 pathway on immune checkpoint vista in pancreatic cancer

Investigational New Drugs - Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors of the pancreas. Preclinical studies show that it evades the immune system with immune...     

Transformation of human mesenchymal stem cells in radiation carcinogenesis: long-term effect of ionizing radiation

Increasing evidence on cancer stem cells suggest that stem cells are susceptive to carcinogenesis and consequently can be the origin of many cancers. We have recently established a telomerase-transduced human mesenchymal stem cell line and subsequently irradiated this in order to achieve malignant transformation. In the present study, we analyzed the long-term effect of ionizing radiation on these cells and investigate whether radiation can trigger tumor development. The cells were irradiated with a low (2.5 Gy) and a high (15 Gy) dose of gamma-rays and followed for up to 6 months after radiation. A subclone of the cells irradiated with 2.5 Gy of gamma-rays formed tumors after implantation to severe combined immunodeficiency mice. During the process of transformation, the cells showed accelerated telomere shortening, increased levels of anaphase bridges and a shift from balanced to unbalanced translocations. The tumor suppressor genes p53 and p21(CIP1) functioned normally throughout the study. Our observations indicate that radiation destabilized the telomeres and that the presence of uncapped telomeres initiated fusion-break-fusion cycles, resulting in increased chromosomal instability and tumor formation. Thus, bone marrow-derived human mesenchymal stem cells are capable of exhibiting a malignant phenotype.     

Direct medical cost of type 1 and type 2 diabetes in Turkey

Diabetes mellitus (DM) is a common chronic metabolic disease with an estimated prevalence of 13.8 % in Turkey. The care and management of patients with DM and its complications consume a substantial proportion of healthcare expenditures. In this study, we aimed to analyse the direct medical cost of type 1 and type 2 diabetes in Turkey. 211 diabetes patients, 36 with type 1 diabetes and 175 with type 2 diabetes, were included in this retrospective study. Their demographic characteristics, laboratory test results, co-morbidities, length of hospital stay, and disease complications were recorded, and their invoices, received from the billing department of the institute, were analysed. The average cost of treatment of diabetes patients was calculated as 607.4 USD. No statistically significant difference was found between the cost of type 1 and type 2 diabetes (P?>?0.05). The costs increased with co-morbidities and complications (P?<?0.05). To reduce the cost of DM treatment, not only health professionals but also patients and their relatives must contribute toward DM management.