Mesenchymal stem cells (MSCs) possess the ability to differentiate into non-mesodermal lineage, and examining their multipotency will be beneficial for application in regenerative medicine. The present study investigated the differentiation capacity into neuronal cells of ectodermal lineage and pancreatic cells of endodermal lineage in each of MSC lines isolated from three samples of human dental papilla tissues (DPSCs). Isolated DPSC lines expressed CD13, CD44, CD73, CD90 and CD105 cell surface markers, and OCT-4, NANOG and SOX-2 transcription factors. Further, all DPSC lines differentiated into osteocytes, adipocytes and chondrocytes of mesodermal lineage, whereas telomerase activity was at a low level in all isolated DPSC lines. Following induction into neuronal cells of ectodermal lineage, the neuron-like morphological alterations and expression of neuro-filament M by immunocytochemical staining was observed in all types of DPSCs, and expression of neuronal cell-specific transcripts, NSE, MAP-2, and NESTIN was further confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Moreover, following induction into pancreatic cells of endodermal lineage, all DPSC lines exhibited morphological alterations with DTZ-positive spheroid clusters, and expression of pancreatic cell-specific transcripts, INSULIN, PDX-1, and GLUT-2, was positively detected by RT-PCR. However, some of these clusters were negatively reacted with DTZ staining. The present results demonstrated that DPSCs exhibit differentiation capacity into neuronal and pancreatic cells of non-mesodermal lineage, and DPSCs could be an alternative source of MSCs for clinical applications.

The present study assessed the cytotoxicity of sodium meta-arsenite (SMA) on telomere shortening and cellular apoptosis in human A-549, MDA-MB-231 and U87-MG cancer cell lines. Following 2 weeks of 1 μM SMA treatment, population doubling time (PDT) was significantly (P < .05) increased by the inhibition of cell proliferation in all the cancer cell lines compared to that in untreated controls. Level of telomerase activity by relative-quantitative telomerase repeat amplification protocol was significantly (P < .05) downregulated by SMA treatment with significant (P < .05) decrease of both telomerase reverse transcriptase and telomerase RNA component transcripts, responsible for telomerase activity. A significant (P < .05) shortening of telomeric repeats by telomere restriction fragment analysis was consequently observed in SMA-treated cells. Moreover, high incidence of cells with senescence-associated β-glucosidase activity was observed in SMA-treated cells and some cells were also differentiated into adipocytes probably due to the loss of tumorous characterizations. Cellular apoptosis proven by DNA fragmentation was observed, and intrinsic apoptotic transcripts (BAX, caspase 3 and caspase 9) and stress-related transcripts (p21, HSP70 and HSP90) were significantly (P < .05) increased in three cancer cell lines treated with SMA. Based on the present study, SMA treatment apparently induced a shortening of telomere length and cytotoxicity, such as induction of cell senescence, apoptosis and cell differentiation. Therefore, we conclude that SMA treatment at specific concentration can lead to gradual loss of tumorous characterizations and can be considered as a potential anti-cancer drug for chemotherapy treatment.

The present study compared the cellular properties based on cell surface differentiation markers, telomerase activity, stem cell-specific transcripts and differentiation capacity into adipocytes, osteocytes and neurocytes in multipotent mesenchymal stem cells (MSCs) isolated from bone marrow (BMSCs), adipose (ASCs), ovarian (OSCs), muscle (MuSCs) and skin (SSCs) tissues of the same donor mini-pig. Using flow cytometry, all isolated MSCs expressed stem cell-positive surface markers CD29, CD44 and Vimentin, at a high level. Using reverse transcription-polymerase chain reaction, BMSCs, ASCs and SSCs showed higher expression of stem cell-specific transcripts (NANOG, OCT-4 and SOX-2) as compared to OSCs and MuSCs. Telomerase activity was detected by relative-quantitative telomerase repeats amplification protocol at a similar level in all MSCs. Further, analysis of cytochemical staining and lineage-specific transcripts demonstrated that all MSCs get easily differentiated into adipocytes, except for OSCs, whereas, BMSCs and MuSCs easily differentiated into osteocytes, compared to ASCs, OSCs and SSCs. Furthermore, all MSC groups showed the same level of capacity for neurocytes differentiation. Based on these results, the cellular properties were dominantly expressed in BMSCs, ASCs and SSCs, whereas the differentiation capacity was dominantly expressed in BMSCs and MuSCs, compared to others MSCs. Taken together, BMSCs could potentially be used as a good source of MSCs for clinical application and fundamental stem cell research.