Dr. Rosalinda Madonna
In this session, cardiologist clinicians and scientists had an opportunity to learn about the potential of induced pluripotent stem (iPS) cells. In the first presentation, Oren Caspi (Israel) introduced the audience to iPS cell derivation methodologies, elucidating limitations and challenges of iPS technology compared to embryonic (ESC) and adult stem cells: immunogenicity, incomplete reprogramming, epigenetic memory and cell heterogeneity. This is a novel area of research of high interest for further exploration. Thus, the true advantage of iPS cells over ESC and adult stem cell needs further elucidation.
Stephanie Dimmeler (Frankfurt, DE) discussed the interplay between stem cell proliferation and differentiation through microRNAs, in particular she showed how miR-34 can prevent iPS cell reprogramming. She went on to discuss interesting personal data about the role of miR-34 in the regulation of cell death, cell apoptosis and cell proliferation, shedding new light on the role of miR-34 as mediator of the effects of ageing on stem cell function. Dimmeler demonstrated that ageing impacts iPS reprogramming efficiency through elevation of miR-34, suggesting that to a certain degree, somatic cells can become too old to receive a reprogramming treatment.
Following these two theoretical lectures the next two speakers, Karl Laugwitz (Munich, DE) and Peter Sartipy (Gothenburg, SE), illustrated to the audience the use of iPS cells as disease modeling and gene correction. In particular, Laugwitz showed interesting personal data about the modeling of CPVT1 syndrome in iPS, a monogenic disease characterized by the mutation S406L in the ryanodin receptor. Sartipy informed the audience on examples of gene correction of disease-causing mutation, in particular genetic engineering of iPS cells using TALE nucleases, site-specific gene correction of point mutation in iPS cells derived from patients with sickle cell disease, and targeted gene correction of α-antitrypsin deficiency. In addition, he called the audience’s attention to the need for standardization of procedures and quality control (QC) for iPS cell research in order to implement the technology on a large industrial scale.
We can look forward with interest to the coming few years as regards the future medical use of iPS cells, which can involve drug discovery (in vitro tools) and regenerative medicine (cell replacement therapy). Certainly, future studies are needed to improve the current understanding of mechanisms regulating genetic reprogramming, which is essential to advance the modeling of human disease in vitro before getting into the clinical arena.
"From bench to practice: induced pluripotent stem cells; in quest of clinical applications"
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