Bone tissue engineering: different gene expression levels between tibial, maxillary and mandibular-derived periosteal cells

Lisanne Groeneveldt
Persbericht

Bone tissue engineering: niet enkel het type cel, ook de plek van afkomst bepaalt wat de cellen doen

Stel dat u een ingreep aan het bot van uw gezicht moet ondergaan vanwege een aangeboren afwijking, een weggehaalde tumor of een trauma. De chirurg bespreekt de ingreep met u: de postoperatieve pijn aan uw gezicht zal vervelend zijn, maar de meeste last zult u ondervinden ter hoogte van uw heup, omdat het nodig is bot uit de heupkam te gebruiken. U kwam enkel met een probleem ter hoogte van uw aangezicht bij de chirurg, maar u vertrekt met een extra probleem in een heel ander deel van uw lichaam. Zou het niet fantastisch zijn als we bot niet van een andere plek van het lichaam hoeven te halen, maar ter plekke kunnen laten groeien? Naar deze methode, bone tissue engineering, wordt veel onderzoek gedaan.

De noodzaak om donorbot te gebruiken bij reconstructieve operaties brengt twee problemen met zich mee. Ten eerste leidt het verkrijgen van donorbot tot forse last in een bijkomend operatiegebied. Hierbij kunnen ook complicaties zoals een bloeding, infectie of zelfs een fractuur optreden. Ten tweede is de hoeveelheid beschikbaar bot via een dergelijke ingreep ook nog eens gelimiteerd. Daarbij is het de vraag of dit bot goed gaat werken. Voor deze problemen biedt bone tissue engineering, naar het Nederlands vertaald als bot weefselbouwkunde, een veelbelovende alternatieve behandelingsoptie. 

Bij bone tissue engineering gebruiken we een combinatie van donorcellen met biomaterialen en chemische stimuli om nieuw weefsel te vormen in het laboratorium. Als we deze techniek voldoende kunnen optimaliseren, kunnen we van een klein stukje donorweefsel heel veel cellen laten groeien. Vervolgens kunnen we deze voorbereiden als botvormende cellen en ze aansluitend transplanteren naar de plaats waar ze nodig zijn. Het verkrijgen van de donorcellen heeft nauwelijks impact op de patiënt, zeker in vergelijking met het transplanteren van een stuk bot. Daarbij is het geproduceerde weefsel ook nog eens beter in de gewenste vorm en grootte te maken met de gewenste eigenschappen qua sterkte en structuur.

cellen1

Voor het optimaliseren van bone tissue engineering is het belangrijk om goed te begrijpen welke donorcellen de beste resultaten geven. De thesis ‘’Bone tissue engineering: Different gene expression levels between tibial, maxillary and mandibular-derived periosteal cells’’ richt zich op precies dit aspect. De belangrijkste veronderstelling hierbij is dat de cellen die verantwoordelijk zijn voor het vormen van botweefsel op een specifieke plaats in het menselijk lichaam, ook het meest geschikt zijn om gebruikt te worden als donorcellen op diezelfde plaats.

Niet elke botvormende cel is hetzelfde.

Er zijn twee natuurlijke situaties waarin het menselijk lichaam botweefsel produceert, namelijk tijdens de embryonale ontwikkeling en bij het herstellen van een breuk. Bij het herstellen van een breuk zijn de cellen in het membraan rondom het bot (het periost) van groot belang. Daarom zijn periostcellen goede donorcellen voor bone tissue engineering. Echter, niet al het botweefsel is hetzelfde. Zo is het bot van de onderkaak bijvoorbeeld heel compact en dat van de bovenkaak heel goed doorbloed. In eerder werk van de kandidate en in deze thesis laten we zien dat ook niet alle periostcellen hetzelfde zijn; hun gedrag is afhankelijk van de plek in het lichaam waar deze cellen worden weggenomen. We hebben hiervoor het gedrag van de periostcellen uit de bovenkaak (maxilla), de onderkaak (mandibula) en het onderbeen (tibia) met elkaar vergeleken. Uit eerder onderzoek van de kandidate is reeds gebleken dat de cellen een verschillende neiging tonen tot botvorming in het laboratorium zelf, maar ook na implantatie in muizen.

cellen2

Om te begrijpen waarom de periostcellen van verschillende locaties andere resultaten geven, kunnen we kijken naar de activiteit van de genen in deze cellen. We hebben aangetoond dat veel genen een verschil in activiteit vertonen tussen deze soorten periostcellen. Vervolgens hebben we gekeken naar welke genen dit betrof. De belangrijkste verschillen werden opgemerkt in de groep genen waarvan bekend is dat ze belangrijk zijn bij de embryonale ontwikkeling. Dit zijn de zogenoemde patroonvormende genen, die ervoor zorgen dat bijvoorbeeld armen en benen op de juiste plekken ontstaan. Deze genen zijn oorspronkelijk ontdekt in het fruitvliegje, de zogenaamde homeobox (HOX) en distal-less homeobox (DLX) genen. 

Het feit dat deze genen nog steeds actief zijn in het periost van 16-30 jarige mensen is een markante ontdekking. Genen die alleen van belang zijn in de embryonale ontwikkeling worden op stil gezet door andere regulerende genen. Dat is bij deze patroonvormende genen blijkbaar niet het geval. Daaruit kunnen we concluderen dat deze genen nog een andere functie moeten hebben. Hierbij kan gedacht worden aan het herstel van botbreuken, omdat dit het andere natuurlijke proces is in het menselijk lichaam waarbij bot wordt gevormd. Deze hypothese wordt ondersteund door het feit dat cellen die HOXA11 activiteit vertonen, leiden tot botvormende cellen na optreden van een breuk. Het is echter nog niet bekend wat de precieze functie is van deze genen bij adolescenten en volwassenen. Verder onderzoek, onder andere via een doctoraat van de kandidate, zal dit moeten uitwijzen.

cellen 3

Er waren ook andere genen waarvan de mate van activiteit in de periostale cellen van de bovenkaak, onderkaak en het onderbeen verschilden. Dit betrof onder meer veel genen die verantwoordelijk zijn voor het vormen van botweefsels. Daaruit kan worden afgeleid dat het al dan niet actief zijn van deze genen bepalend is voor de kwaliteit van het botvormingsproces. Aangezien veel van de gevonden genen die in verschillende mate actief zijn tussen de drie soorten periostcellen een effect hebben op de botvorming, is deze kennis zeer waardevol voor het optimaliseren van bone tissue engineering.

Het onderzoek van de thesis ‘’Bone tissue engineering: Different gene expression levels between tibial, maxillary and mandibular-derived periosteal cells’’ beantwoordt aldus belangrijke vragen. De uitkomsten hebben gevolgen voor zowel klinische toepassing als fundamentele wetenschappelijke kennis die deze vooruitgang mogelijk maakt. Tegelijkertijd roepen de resultaten van deze thesis vragen op die het onderwerp zijn van verder onderzoek. Met deze thesis hebben we een belangrijke stap gezet richting het moment waarop de chirurg bone tissue engineering in de praktijk kan toepassen.

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Universiteit of Hogeschool
Master in de tandheelkunde
Publicatiejaar
2019
Promotor(en)
Prof. Dr. C. Politis
Kernwoorden
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