Adult stem cells : hopes and hypes of regenerative medicine

Stem cells are self-renewing cells that can differentiate into specialized cell type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) differentiate into cells of all three embryonic lineages. Multipotent stem cells, like hematopoietic stem cells (HSC), can develop into multiple specialized cells in a specific tissue. Unipotent cells differentiate only into one cell type, like e.g. satellite cells of skeletal muscle. There are many examples of successful clinical applications of stem cells. Over million patients worldwide have benefited from bone marrow transplantations performed for treatment of leukemias, anemias or immunodeficiencies. Skin stem cells are used to heal severe burns, while limbal stem cells can regenerate the damaged cornea. Pluripotent stem cells, especially the patient-specific iPSC, have a tremendous therapeutic potential, but their clinical application will require overcoming numerous drawbacks. Therefore, the use of adult stem cells, which are multipotent or unipotent, can be at present a more achievable strategy. Noteworthy, some studies ascribed particular adult stem cells as pluripotent. However, despite efforts, the postulated pluripotency of such events like "spore-like cells", "very small embryonic-like stem cells" or "multipotent adult progenitor cells" have not been confirmed in stringent independent studies. Also plasticity of the bone marrow-derived cells which were suggested to differentiate e.g. into cardiomyocytes, has not been positively verified, and their therapeutic effect, if observed, results rather from the paracrine activity. Here we discuss the examples of recent studies on adult stem cells in the light of current understanding of stem cell biology

Reversible inhibition of reproduction during regeneration of cerebral ganglia and celomocytes in the earthworm Dendrobaena veneta

Earthworms may be subjected to mechanical/chemical stimuli and/or sub-lethal predator attacks leading to the extrusion of celomocytes and/or loss of body parts; thus, regeneration of cells, tissues and organs has adaptive value. The aim of present study on the lumbricid earthworm Dendrobaena veneta was to determine the interactive effects of celomocytes and the brain on the regeneration of either system after experimental depletion or extirpation, and to assess the effects of such treatments on reproductive performance. Decerebration was achieved either by amputating the first six anterior segments, or by surgery; celomocyte depletion was achieved by a standard electro-stimulation procedure. Celomocytes (amebocyte and eleocytes, respectively) were counted by hemocytometry, and riboflavin content in celomocyte lysates measured by spectrofluorimetry. The main findings were: (i) D. veneta regenerated anatomically intact brain, including neurosecretory cells, within 10 - 18 weeks after its removal plus celomocyte depletion (i.e. dual treatment); (ii) amoebocyte counts recovered to control levels by 10 weeks after extrusion treatment alone, but were still lower (60 %) than in controls at 18 weeks after dual treatment; eleocyte recovery after electro-stimulation alone was slow, reaching control levels only after 18 weeks, and was further retarded (31 % of controls at 18 weeks) by brain extirpation; (iii) riboflavin content was lower than controls only in the dual-treatment worms at 5 weeks; riboflavin content relative to eleocyte numbers was initially higher than controls in both treatment groups; this index was restored to control levels by 18 weeks in the electro-stimulation only treatment whilst recovery was somewhat retarded in the brain-extirpated group; (iv) celomocyte depletion treatment alone slightly impaired reproductive output, whilst brain removal had pronounced and protracted inhibitory effects. The observations engender the hypothesis that brain-derived neurosecretions and immune-competent celomocytes act in tandem to modulate neural regeneration and reproduction

Clock and clock-controlled genes are differently expressed in the retina, lamina and in selected cells of the visual system of Drosophila melanogaster

The retina and the first optic neuropil (lamina) of Drosophila show circadian rhythms in various processes. To learn about the regulation of circadian rhythms in the retina and lamina and in two cell types, glial and the lamina L2 interneurons, we examined expression of the following clock genes; per, tim, clk, and cry and clock-controlled genes (ccgs); Atpα, nrv2, brp, Pdfr. We found that the expression of gene studied is specific for the retina and lamina. The rhythms of per and tim expression in the retina and glial cells are similar to that observed in the whole head and in clock neurons, while they differ in the lamina and L2 cells. In both the retina and lamina, CRY seems to be a repressor of clk expression. In L2 interneurons per expression is not cyclic indicating the other function of PER in those cells than in the circadian molecular clock. In contrast to per and tim, the pattern of clk and cry expression is similar in both the retina and lamina. The retina holds the autonomous oscillators but the expression of cry and ccgs, Atpα and nrv2, is also regulated by inputs from the pacemaker transmitted by PDF and ITP neuropeptides

Preliminary analysis of the expression of selected proangiogenic and antioxidant genes and MicroRNAs in patients with non-muscle-invasive bladder cancer

Heme oxygenase-1 (HO-1) is an enzyme contributing to the development and progression of different cancer types. HO-1 plays a role in pathological angiogenesis in bladder cancer and contributes to the resistance of this cancer to therapy. It also regulates the expression of microRNAs in rhabdomyosarcoma and non-small cell lung cancer. The expression of HO-1 may be regulated by hypoxia inducible factors (HIFs) and Nrf2 transcription factor. The expression of HO-1 has not so far been examined in relation to Nrf2, HIF-1α, and potential mediators of angiogenesis in human bladder cancer. We measured the concentration of proinflammatory and proangiogenic cytokines and the expression of cytoprotective and proangiogenic mRNAs and miRNAs in healthy subjects and patients with bladder cancer. HO-1 expression was upregulated together with HIF-1α, HIF-2α, and Nrf2 in bladder cancer in comparison to healthy tissue. VEGF was elevated both at mRNA and protein level in the tumor and in sera, respectively. Additionally, IL-6 and IL-8 were increased in sera of patients affected with urothelial bladder cancer. Moreover, miR-155 was downregulated whereas miR-200c was elevated in cancer biopsies in comparison to healthy tissue. The results indicate that the increased expression of HO-1 in bladder cancer is paralleled by changes in the expression of other potentially interacting genes, like Nrf2, HIF-1α, HIF-2α, IL-6, IL-8, and VEGF. Further studies are necessary to also elucidate the potential links with miR-155 and miR-200c