| Abstract | Neuralne matične stanice generiraju neurone, astrocite i oligodendrocite u mozgu tijekom cijelog života. Najaktivnije su tijekom prenatalnog razvoja u procesu stvaranja živčanog sustava, dok u odrasloj dobi postoje u dvije regije mozga: subgranularnoj i subventrikularnoj. Matične stanice u subgranularnoj zoni nazivamo stanicama tipa 2, dok su to u subventrikularnoj zoni stanice tipa B. Asimetričnom diobom matičnih stanica nastaju progenitori; stanice tipa 1 u subgranularnoj i stanice tipa C u subventrikularnoj zoni. Neuroblasti nastaju diobom progenitora, a nazivamo ih stanicama tipa A, tj. stanicama tipa 3. Posljednji korak diferencijacije je stvaranje nezrelih neurona iz neuroblasta, nakon čega slijedi njihovo sazrijevanje i stvaranje sinapsi.
Otkriće neuralnih matičnih stanica omogućilo je značajan napredak u in vitro istraživanjima s obzirom da se neuroni, koji su post-mitotičke stanice vrlo teško kultiviraju. Kulture neuralnih matičnih stanica mogu se proizvesti na nekoliko načina iz embrionalnih matičnih stanica i induciranih pluripotentnih matičnih stanica. Rezultat kultivacije mogu biti 2D neuralne rozete i monokultura ili 3D neurosfere i organoidi.
Osim in vitro istraživanja, in vivo studije su dodatno razjasnile regulaciju matičnih stanica u neurogenim nišama u kojima se nalaze neuroni, glijalne i ependimalne stanice. Sve stanice prisutne u neurogenoj niši luče signalne molekule te tako utječu na održavanje, proliferaciju i diferencijaciju neuralnih matičnih stanica. Također, unutarnji regulatori poput transkripcijskih faktora, epigenetskih modifikacija i metaboličkih putova, potiču ili inhibiraju samoobnavljanje ili diferencijaciju.
Dosad je poznato samo nekoliko funkcija neurona nastalih u odrasloj dobi, ali poznato je da njihova ekscitabilnost i plastičnost omogućuju različite funkcije. Uključeni su u pamćenje i učenje, razlikovanje sličnih događaja i okruženja, kao i u odgovor na stres.
U liječenju neurodegenerativnih bolesti, ishemičnog moždanog udara i depresije također je prepoznata važnost neuralnih matičnih stanica. Neurodegenerativne bolesti i moždani udar su stanja u kojima dolazi do odumiranja neurona i propadanja tkiva te je transplantacija neuralnih matičnih stanica potencijalna terapija u njihovom liječenju. Do njihovog korištenja u terapijske svrhe moraju se otkriti preostale nepoznanice regulacije i funkcije adultne neurogeneze. |
| Abstract (english) | Neural stem cells generate neurons, astrocytes and oligodendrocytes in the brain throughout life. They are most active during prenatal development in the process of formation of the nervous system, while in adulthood they exist in two regions: subgranular and subventricular zone. Stem cells in the subgranular zone are called type 2 cells, while in the subventricular zone they are called type B cells. The asymmetric division of stem cells creates progenitors; type 1 cells in the subgranular and type C cells in the subventricular zone. Neuroblasts are created by the division of progenitors, and we call them type A cells and type 3 cells, respectively. The last step of differentiation is the creation of immature neurons from neuroblasts, followed by their maturation and formation of synapses.
The discovery of neural stem cells enabled significant progress in in vitro research, given that neurons, which are post-mitotic cells, are very difficult to cultivate. Neural stem cell cultures can be produced in several ways from embryonic stem cells and induced pluripotent stem cells. The result of cultivation can be 2D neural rosettes and monoculture or 3D neurospheres and organoids.
In addition to in vitro research, in vivo studies have elucidated the regulation of stem cells in neurogenic niches where neurons, glial and ependymal cells reside. All cells present in the niche by secreting signaling molecules influence the maintenance, proliferation and differentiation of neural stem cells. Also, internal regulators such as transcription factors, epigenetic modifications and metabolic pathways promote or inhibit self-renewal or differentiation.
So far, only a few functions of adult-born neurons are known, but it is known that their excitability and plasticity enable distinct functions. They are involved in memory and learning, pattern separation as well as the stress response.
The importance of neural stem cells in the treatment of neurodegenerative diseases, ischemic stroke and depression was discovered. Neurodegenerative diseases and stroke are conditions in which neurons die and tissue decay, and neural stem cell transplantation is a potential therapy in their treatment. Until their use for therapeutic purposes, the remaining unknowns of the regulation and function of adult neurogenesis must be discovered. |
