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The success rate of regenerative medicine largely depends on the type of stem cells applied in such procedures. Consequently, to achieve the needed level for clinical standardization, we need to investigate the viability of accessible sources with sufficient quantity of cells. Since the oral region partly originates from the neural crest, which naturally develops in niche with decreased levels of oxygen, the main goal of this work was to test if human oral mucosa stem cells (hOMSC) might be used to treat neurons damaged by anoxia. Here we show that hOMSC are more resistant to anoxia than human induced pluripotent stem cells and that they secrete BDNF, GDNF, VEGF and NGF. When hOMSC were added to human neurons damaged by anoxia, they significantly improved their survival. This regenerative capability was at least partly achieved through miR-514A-3p and SHP-2 and it decreased in hOMSC exposed to neural cells for 14 or 28 days. In addition, the beneficial effect of hOMSC were also confirmed in mice affected by stroke. Hence, in this work we have confirmed that hOMSC, in a time-limited manner, improve the survival of anoxia-damaged neurons and significantly contribute to the recovery of experimental animals following stroke.

Populations around the world are ageing faster than ever in the past. A constant and already impressive rate in the worldwide increase of life expectancy has led to the fact that the current proportion of the population above 60 years (17%) will double in the next thirty to forty years. In the next 30 years, every third person in the world will fall into the category of a senior citizen. This demographic transition will have an impact on almost all aspects of society and requires a complete and well-defined shift in the paradigm in the medical, social, and technological fields.

Razvoj kaudalnog dijela zametka kralješnjaka odvija se nakon završetka gastrulacije i nestanka primitivne pruge sekundarnim mehanizmom razvoja, tijekom kojeg strukture osnove repa nastaju od nediferenciranih stanica repnog pupoljka. Kaudalni dio zametka poremećen je u mišjih mutanata splotch i truncate. U splotch miševa mutiran je gen Pax3, što ima za posljedicu otvorenu neuralnu cijev (spina bifida) i poremećaj migracije stanica neuralnog grebena. U truncate miševa mutiran je gen Noto, gdje je poremećen razvoj notokorda. Hipoteza ovog istraživanja bila je da je fenotip mutiranih miševa splotch i truncate posljedica nepravilnog razvoja repnog pupoljka, te poremećenog sekundarnog mehanizma razvoja. Cilj rada bio je usporediti razvoj kaudalnog dijela zametka visoko srođenog soja C57Bl/6 s poremećenim razvojem mutanata splotch i truncate. Građa mišjih zametaka starih od 9 do 12,5 dana proučavana je svjetlosnom mikroskopijom serijskih polutankih rezova obojanih toluidinskim modrilom. U zamecima C57Bl/6 miševa sekundarni mehanizam razvoja obuhvaća postupnu diferencijaciju stanica repnog pupoljka, koje se dijele na moždinski tračak od kojeg nastaje sekundarna neuralna cijev, i repni tračak od kojeg nastaje notokord i repno crijevo. Poremećena neurulacija u splotch zametaka nije praćena poremećajem građe repnog pupoljka, osim u splotch zametaka starih 12,5 dana, gdje dolazi do sveobuhvatnog poremećaja razvoja osnove repa kaudalno od spine bifide. Spina bifida u splotch zametaka nastaje na prijelazu iz primarne u sekundarnu neuralnu cijev. U truncate zametaka djelomično nedostaje notokord. Diferencijacija repnog pupoljka je poremećena, te se notokord umjesto od repnog tračka odvaja od ventralne strane sekundarne neuralne cijevi. Dorzalni dio repnog tračka umjesto notokorda oblikuje dodatni lumen repnog crijeva. Nedostatak notokorda u osnovi repa povezan je s poremećajem razvoja susjednih struktura, neuralne cijevi i somita. Opisana morfogenetska zbivanja doprinose razumijevanju razvojnih poremećaja u čovjeka - spine bifide, sindroma kaudalne disgeneze i Waardenburgovog sindroma.