Tissue renewal is a well-known phenomenon by which old and dying-off cells of various tissues of the body are replaced by progeny of local or circulating stem cells (SCs). An interesting question is whether donor SCs are capable to prolong the lifespan of an aging organism by tissue renewal. In this work, we investigated the possible use of bone marrow (BM) SC for lifespan extension. To this purpose, chimeric C57BL/6 mice were created by transplanting BM from young 1.5-month-old donors to 21.5-month-old recipients. Transplantation was carried out by means of a recently developed method which allowed to transplant without myeloablation up to 1.5 × 108 cells, that is, about 25% of the total BM cells of the mouse. As a result, the mean survival time, counting from the age of 21.5 months, the start of the experiment, was +3.6 and +5.0 (±0.1) months for the control and experimental groups, respectively, corresponding to a 39 ± 4% increase in the experimental group over the control. In earlier studies on BM transplantation, a considerably smaller quantity of donor cells (5 × 106) was used, about 1% of the total own BM cells. The recipients before transplantation were exposed to a lethal (for control animals) X-ray dose which eliminated the possibility of studying the lifespan extension by this method.
Background::
One of the approaches to cancer gene therapy relies on tumor transfection with DNA encoding tox-ins under control of tumor-specific promoters.
Methods::
Here we used DNA plasmids encoding very potent anti-ERBB2 targeted toxin, driven by the human telomerase promoter or by the ubiquitous CAG promoter (pTERT-ETA and pCAG-ETA) and linear polyethylenimine to target cancer cells.
Results::
We showed that the selectivity of cancer cell killing by pTERT-ETA plasmid is highly dependent upon method of preparation of DNA- polyethylenimine complexes. After adjustment of complex preparation protocol cell lines with high ac-tivity of telomerase promoter can be selectively killed by transfection with pTERT-ETA plasmid. We also show that cells transfected with pTERT-ETA and pCAG-ETA plasmids do not exert any detectable bystander effect in vitro.
Conclusion::
Despite this, three intratumoral injections of a plasmid- polyethylenimine complex resulted in a substantial growth retardation of poorly transfectable D2F2/E2 tumor in mice. There were no significant differences in anti-tumor prop-erties between DNA constructs with telomerase or CAG promoters in vivo.
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