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Adult stem cells: hopes and hypes of regenerative medicine

100%

Dulak J., Szade K., Szade A., Nowak W., Józkowicz A.

Acta Biochimica Polonica

2015

vol. 62

issue 3

329-337

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.

Heme oxygenase-1 expression in disease states.

100%

Deshane J., Wright M., Agarwal A.

Acta Biochimica Polonica

2005

vol. 52

issue 2

273-284

Heme oxygenase-1 (HO-1) is an enzyme which catalyzes the rate-limiting step in heme degradation resulting in the formation of iron, carbon monoxide and biliverdin, which is subsequently converted to bilirubin by biliverdin reductase. The biological effects exerted by the products of this enzymatic reaction have gained much attention. The anti-oxidant, anti-inflammatory and cytoprotective functions associated with HO-1 are attributable to one or more of its degradation products. Induction of HO-1 occurs as an adaptive and beneficial response to several injurious stimuli including heme and this inducible nature of HO-1 signifies its importance in several pathophysiological disease states. The beneficial role of HO-1 has been implicated in several clinically relevant disease states involving multiple organ systems as well as significant biological processes such as ischemia-reperfusion injury, inflammation/immune dysfunction and transplantation. HO-1 has thus emerged as a key target molecule with therapeutic implications.

Pharmacological versus genetic inhibition of heme oxygenase-1 - the comparison of metalloporphyrins, shRNA and CRISPR/Cas9 system

86%

Mucha O., Podkalicka P., Czarnek M., Biela A., Mieczkowski M., Kachamakova-Trojanowska N., Stepniewski J., Jozkowicz A., Dulak J., Loboda A.

Acta Biochimica Polonica

2018

vol. 65

issue 2

277-286

Inhibition of heme oxygenase-1 (HO-1, encoded by HMOX1), a cytoprotective, anti-apoptotic and anti-inflammatory enzyme, may serve as a valuable therapy in various pathophysiological processes, including tumorigenesis. We compared the effect of chemical inhibitors - metalloporphyrins, with genetic tools - shRNA and CRISPR/Cas9 systems, to knock-down (KD)/knock-out (KO) HO-1 expression/activity. 293T cells were incubated with metalloporphyrins, tin and zinc protoporphyrins (SnPPIX and ZnPPIX, respectively) or were either transduced with lentiviral vectors encoding different shRNA sequences against HO-1 or were modified by CRISPR/Cas9 system targeting HMOX1. Metalloporphyrins decreased HO activity but concomitantly strongly induced HO-1 mRNA and protein in 293T cells. On the other hand, only slight basal HO-1 inhibition in shRNA KD 293T cell lines was confirmed on mRNA and protein level with no significant effect on enzyme activity. Nevertheless, silencing effect was much stronger when CRISPR/Cas9-mediated knock-out was performed. Most of the clones harboring mutations within HMOX1 locus did not express HO-1 protein and failed to increase bilirubin concentration after hemin stimulation. Furthermore, CRISPR/Cas9-mediated HO-1 depletion decreased 293T viability, growth, clonogenic potential and increased sensitivity to H2O2 treatment. In summary, we have shown that not all technologies can be used for inhibition of HO activity in vitro with the same efficiency. In our hands, the most potent and comprehensible results can be obtained using genetic tools, especially CRISPR/Cas9 approach.

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3 Acta Biochimica Polonica

1 2018

1 2015

1 2005

2 Dulak J.

1 Agarwal A.

1 Biela A.

1 Czarnek M.

1 Deshane J.

1 Jozkowicz A.

1 Józkowicz A.

1 Kachamakova-Trojanowska N.

1 Loboda A.

1 Mieczkowski M.

1 Mucha O.

1 Nowak W.

1 Podkalicka P.

1 Stepniewski J.

1 Szade A.

1 Szade K.

1 Wright M.

Search results

Adult stem cells: hopes and hypes of regenerative medicine

Heme oxygenase-1 expression in disease states.

Pharmacological versus genetic inhibition of heme oxygenase-1 - the comparison of metalloporphyrins, shRNA and CRISPR/Cas9 system