Ex vivo gene transfer to full thickness wounds. A platform for autologous 'smart' tissue engineering for tissue repair.

Jan Vranckx
Slimme cellen genezen diepe wonden.
 
Grote wonden vergen complexe behandelingen. Een onderzoeksteam van Plastische Chirurgen in het UZ-Leuven is erin geslaagd om diepe wonden te repareren met autologe (lichaamseigen) ‘smart tissue engineering’. Bij varkens is het een succes. Nu mensen nog.
 
Derdegraads brandwonden, uitgebreide verwondingen na verkeersongevallen of na een operatie vanwege kanker, de plastisch reconstructief chirurg wordt er dagelijks mee geconfronteerd.

Ex vivo gene transfer to full thickness wounds. A platform for autologous 'smart' tissue engineering for tissue repair.

Slimme cellen genezen diepe wonden.

 

Grote wonden vergen complexe behandelingen. Een onderzoeksteam van Plastische Chirurgen in het UZ-Leuven is erin geslaagd om diepe wonden te repareren met autologe (lichaamseigen) ‘smart tissue engineering’. Bij varkens is het een succes. Nu mensen nog.

 

Derdegraads brandwonden, uitgebreide verwondingen na verkeersongevallen of na een operatie vanwege kanker, de plastisch reconstructief chirurg wordt er dagelijks mee geconfronteerd. Vaak is een complexe chirurgische weefsel transplantatie nodig die op zich een oorzaak is van nieuwe verwonding daar waar het donor weefsel genomen werd. Maar wanneer zulke uitgebreide behandeling niet wordt uitgevoerd, zijn stugge littekens het gevolg en die leiden al te vaak tot forse bewegingsbeperking rond gewrichten en verminderde motivatie van de patiënt voor sociale reïntegratie na het ongeval.

Bij sommige erg complexe defecten, zoals zeer uitgebreide diepe brandwonden, is er zelfs geen echt degelijke oplossing. De sinds lang gebruikte huidgreffen zijn dun en vertegenwoordigen enkel de oppervlakkige laag van huid. De recent ontwikkelde ‘dermale’ kunsthuid, die de diepere laag van de huid vertegenwoordigt, kan dienen als een tapijtje waarop huidgreffen kunnen gelegd worden. Die kunstdermis is nog steeds dun en vermits ze samengesteld is uit bindweefsel van koeien of varkens,wordt ze geleidelijk afgebroken eens op een wonde geplaatst bij de mens.

 

Jan Vranckx van de Universiteit van Leuven promoveerde op een strategie die huiddefecten behandelt met “autologe (lichaamseigen),elastische,goed doorbloede huid van volledige dikte”. Autologe smart tissue engineering, heet deze strategie.

 

‘Smart tissue engineering’ start met het kweken van cellen uit de verschillende huidlagen en van lichaamseigen oorsprong. “Ook deze methode bestaat al 20 jaar maar heeft tot weinig geleid”, zegt Vranckx. Om deze cellen een volwaardige elastische huid te doen vormen is heel wat meer nodig. “ Zie de wonde als een constructie site; je hebt bouwmateriaal nodig, mankracht maar ook een coördinator, een architect. In de wondheling fungeren groei-eiwitten ,groeifactoren, als de coördinators. Deze eiwitten worden afgescheiden door alle cellen die iets in de helende wonde te betekenen hebben. Bij ziekte of na trauma is de aanmaak van die groeifactoren fors verminderd, hoewel ze net dan meest benodigd zijn.

Vranckx: “Die groeifactoren zijn erg belangrijk vanaf het prille begin van de wondheling, van de vorming van stolsel en nieuwe bloedvaatjes in de wonde tot het zacht en wit worden van het litteken. Die groeifactoren gebruiken om de wondheling te bevorderen is dus een logische stap”.

Helaas worden die groeifactoren snel afgebroken als je ze simpelweg in de wonde zou spuiten. Dit kan omzeild worden door de cellen zélf als miniproductie eenheden de eiwitten te laten aanmaken.

Vranckx:” Nadat we in het labo het DNA van de groeifactor naar keuze in de huidcellen hebben aangebracht wordt dit DNA in de cel zelf vertaald naar het groeifactor eiwit dat dan in de wonde wordt afgescheiden; niet éénmalig maar constant. De cellen vormen zich in de wonde als kleine fabriekjes van de groeifactoren.

Om deze strategie optimaal te laten verlopen, focust Vranckx op stam cellen van de huid.“Zulke cellen zijn in staat om op 4 weken tijd uit 10 cm2 zoveel cellen te produceren dat de ganse huid oppervlakte van de mens zou kunnen bedekt worden. Evengoed kunnen die cellen fungeren als dragers van die groeifactoren die in wondheling een groot verschil kunnen maken”.

Deze strategie leidde in een varkensmodel tot snelle heling met laag per laag goed doorbloed weefsel. “Deze doorbloeding is het grote verschil met eerder voorgestelde behandelingsmethoden door tissue engineering” zegt Vranckx. De fusie van tissue engineering technieken met gen therapie brengt ons een hele stap verder in die zoektocht naar tissue engineering van weefsels en zelfs organen.

Hoe lang het nog duurt alvorens we ‘lichaamseigen weefsel als ‘take away’ kunnen  bestellen en gebruiken is onvoorspelbaar.

De euforie was nabij toen eind jaren ‘90 op een ‘naakt muismodel’ een mensen oor werd gegroeid. Door tissue engineering leek toen alles mogelijk. Dit oor was slechts een matrix in de vorm van een oorschelp, die onder de erg elastische en dunne huid van die muizensoort werd gehecht. Die matrix werd natuurlijk in korte tijd overwoekerd met littekenweefsel en bloedvaatjes en bij de muis niet afgestoten. Vranckx:“Zowel bij varken als mens komen we geen stap verder als het weefsel, aangemaakt door tissue engineering, niet goed doorbloed is en niet lichaamseigen. Met de huidige wereldwijde ambitie en motivatie in tissue engineering lijkt me nog een 10-tal jaar voor authentieke huid op bestelling rationeel.”

Tot dan je hand er zeker niet voor in het vuur steken.

 

 

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