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Τα τελευταία χρόνια υπάρχει μεγάλο ενδιαφέρον για τη βιολογία των σωματικών βλαστικών κυττάρων (adult stem cells) εξαιτίας της ικανότητας τους να αυτοανανεώνονται καθώς επίσης και της πλαστικότητας την οποία εμφανίζουν. Οι ιδιότητες αυτές καθιστούν τα σωματικά βλαστικά κύτταρα ικανά να παράγουν προγόνους διαφόρων τύπων ωρίμων κυττάρων, οι οποίοι συμμετέχουν ενεργά στη διατήρηση της ομοιόστασης ιστών και οργάνων τόσο κατά τη φυσιολογική πορεία της ζωής τους όσο και σε περίπτωση βλάβης. Εν γένει τα εμβρυικά και σωματικά βλαστικά κύτταρα φαίνεται να εμφανίζουν όμοιες λειτουργίες όσον αφορά στην ικανότητα αυτοανανέωσης και στην ιδιότητα τους να παράγουν διαφοροποιημένους κυτταρικούς προγόνους διαφόρων κυτταρικών σειρών τόσο σε απλοποιημένες συνθήκες καλλιέργειας in vitro όσο και μετά από μεταμόσχευσή τους σε ξενιστή in vivo. Πιο συγκεκριμένα η εδραίωση των ιδιοτήτων των βλαστικών και προγονικών κυττάρων in vitro και in vivo παρείχε τις ενδείξεις της συμμετοχής τους στην ανανέωση των ιστών μετά από βλάβη. Για το λόγο αυτό η χρήση τους αποτελεί πολλά υποσχόμενη στρατηγική στην κυτταρική και γενετική θεραπευτική πολλών εκφυλιστικών νοσημάτων καθώς επίσης και ως επικουρική ανοσοθεραπεία για διαφορους επιθετικούς τύπους καρκίνου. Η νόσος του Parkinson, η νόσος του Alzheimer, οι μυικές εκφυλιστικές διαταραχές, χρόνια ηπατικά νοσήματα, η καρδιακή ανεπάρκεια, ο σακχαρώδης διαβήτης τύπου I και τύπου II καθώς επίσης και διάφορες δερματικές, οφθαλικές, νεφρικές και αιμοποιητικές διαταραχές θα μπορούσαν να αντιμετωπιστούν με θεραπείες βασιζόμενες σε βλαστικά κύτταρα. Γενετικές μεταβολές ή/και επίμονη ενεργοποίηση διακριτών αναπτυξιακών μονοπατιών οι οποίες είναι δυνατόν να παρατηρούνται σε μειοψηφία σωματικών βλαστικών και προγονικών κυττάρων μπορούν, σε ορισμένες περιπτώσεις, να οδηγήσουν σε ογκογόνο μεταλλαγή. Το φαινόμενο αυτό εμπλέκει την ενεργοποίηση κυτταρικών μονοπατιών τα οποία σηματοδοτούνται από διάφορους αυξητικούς παράγοντες και ενέχουν σημαντική θέση στην αύξηση και επιβίωση καρκινικών κυττάρων. Πιο συγκεκριμένα η θετική ρύθμιση μονοπατιών που αφορούν στον EGF, hedgehog, Wnt/β-κατενίνη και του Νοtch αποτελούν κρίσιμης σημασίας γεγονότα για την έναρξη και προαγωγή επιθετικών τύπων κακοήθειας όπως η οξεία λευχαιμία και το λέμφωμα, ο καρκίνος του εγκεφάλου, του δέρματος, του πνεύμονα, του οισοφάγου, του στομάχου, του παγκρέατος, του ήπατος, του μαστού, των ωοθηκών, του προστάτη και των όρχεων. Για το λόγο αυτό η μοριακή στόχευση αυτών των ογκογόνων σηματοδοτικών στοιχείων αποτελεί πολλά υποσχόμενη προσέγγιση για την ανάπτυξη νέων θεραπευτικών συνδιασμών εναντίων μεταστατικών μορφών καρκίνου. / Stem cell biology and their role in lung homeostasis, tissue repair and cancer.

Skin-derived precursors (SKPs) are multipotent dermal stem cells that reside within a hair follicle niche and that share properties with embryonic neural crest precursors. Here, we have asked whether SKPs and their endogenous dermal precursors originate from the neural crest or whether, like the dermis itself, they originate from multiple developmental origins. To do this, we used two different mouse Cre lines that allow us to perform lineage tracing: Wnt1-cre, which targets cells deriving from the neural crest, and Myf5-cre, which targets cells of a somite origin. By crossing these Cre lines to reporter mice, we show that the endogenous follicle-associated dermal precursors in the face derive from the neural crest, and those in the dorsal trunk derive from the somites, as do the SKPs they generate. Despite these different developmental origins, SKPs from these two locations are functionally similar, even with regard to their ability to differentiate into Schwann cells, a cell type only thought to be generated from the neural crest. Analysis of global gene expression using microarrays confirmed that facial and dorsal SKPs exhibit a very high degree of similarity, and that they are also very similar to SKPs derived from ventral dermis, which has a lateral plate origin. However, these developmentally distinct SKPs also retain differential expression of a small number of genes that reflect their developmental origins. Thus, an adult neural crest-like dermal precursor can be generated from a non-neural crest origin, a finding with broad implications for the many neuroendocrine cells in the body.

Both cDNA tag-based and DNA chip hybridization assays have revealed widespread transcriptional activity across mammalian genomes, providing a rich source of novel protein-coding and non-coding transcripts. Annotation and functional evaluation of this undefined transcriptome space represents a major step towards the comprehensive definition of biomolecules regulating the properties of living cells, including embryonic stem cells (ESCs) and their derivatives. In this study I analysed 87 rare mRNA transcripts from human ESCs that mapped uniquely to the human genome, in regions lacking evidence for known genes or transcripts. In addition, the transcripts appeared enriched in the hESC transcriptome as enumerated by serial analysis of gene expression (SAGE). Full-length transcripts corresponding to twelve novel LongSAGE tags were recovered and evaluated with respect to gene structure, protein-coding potential, and gene regulatory features. In addition, transcript abundance was compared between RNA isolated from undifferentiated hESCs and differentiated cells. Analysis of full-length transcripts revealed that the novel ORFs did not exceed a size of 129 amino acids and no matches were observed to well characterized protein domains. Interesting protein level predictions included small disulfide-bonded proteins, known members of which are important in a variety of biological processes. Transcripts evaluated for differential expression by real-time RT-qPCR (Reverse Transcription followed by real-time quantitative Polymerase Chain Reaction) were found to be variably expressed (0.2- to 4.5-fold) in Day-2 or Day-4 retinoic acid-induced differentiation cultures compared to undifferentiated hESCs. Relative quantitation using a universal reference RNA (derived from pooled adult tissues) showed large differences in novel transcript levels (0.002- to 35-fold) compared to hESCs. Collectively, these results provide a detailed analysis of a set of novel hESC transcripts and their abundance in early and adult differentiated cell types, both of which may advance our understanding of the transcriptional events governing stem cell behavior.

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Physiological electric fields (EFs) have been measured in many developing and regenerating systems and are modulated spatially, temporally and in magnitude.  Many types of cells polarize and migrate in specific directions when exposed to a small applied EF similar in magnitude to those found endogenously.  In the present investigation, an endogenous EF was recorded in an aortic explant.  The response of three EPCs (MFLM-4, AEL-deltaR1 and AEL-deltaR1/Runx1), one endothelial cell line (HUVEC) and five other cell lines (MDA-MB-231, MTLn-3, HEK-293, COS-7 and CHO) in physiological EFs were shown.  The roles of vascular endothelial growth factor receptor 2 (VEGFR2) and voltage-gated potassium (Kv) channels in the EFs directed cell migration were studied.  The roles of intracellular calcium, intracellular calcium stores, purinergic signalling and gap junction communication in the intracellular calcium rising, calcium wave propagation and re-endothelialization were studied too.  In conclusion, electrical signalling between cells and ionic fluxes in cells are important controlling mechanisms of endothelial behaviours.  Electric fields and ionic fluxes regulate migration of endothelial cells and endothelial progenitor cells.  Orchestrated endothelial behaviours and recruitment of endothelial progenitor cells repair injuries to endothelium, and may lead to angiogenesis.  Manipulation of electric fields and control of ionic fluxes may be a promising approach to control endothelial cell migration and angiogenesis.

Stem cell therapy is emerging as a possible method for treating many diseases and disorders, such as cardiovascular disease. In particular, stem cells may be able to revive the dead tissue caused by acute myocardial infarction (heart attack). Adipose-derived stem cells were labelled with 18F-fluorodeoxyglucose (FDG) and superparamagnetic iron oxide (SPIO) particles, for imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), respectively, and injected into several rats following induced myocardial infarction. Stem cell retention in the heart was investigated following three injection sites; two within the heart (intramyocardial and left intraventricular), and one easily accessible vein (tail vein). The PET and MR images were registered and the initial distributions analyzed using region of interest (ROI) analysis, to determine which injection method would result in the highest stem cell retention in the infarcted heart. The ROI results determined that the intramyocardial injection had the highest % injected dose (%ID) in the heart with 14 +/- 4%, followed by left intraventricular and tail vein with %IDs of 3.6 +/- 0.8% and 1.2 +/- 0.6%, respectively. The results indicate that stem cell delivery via intramyocardial injection should be utilized for optimal retention in the heart.