Lesioni cartilaginee a carico di articolazioni molto sollecitate, come le ginocchia, sono frequenti nella popolazione e colpiscono soggetti di ogni età. Un gruppo del Centro di Ricerca e Applicazione sulle cellule hiPS (staminali pluripotenti indotte) dell’Università di Kyoto ha sviluppato un nuovo protocollo per la produzione di cartilagini a partire dalle iPS-cell che potrebbe rivoluzionare il trattamento delle lesioni articolari.
La cartilagine è una forma specializzata di tessuto connettivo di sostegno costituita da condrociti e da matrice extra cellulare (ECM) da essi prodotta; se ne possono distinguere tre tipi con composizione della ECM, distribuzione e funzioni diverse: la cartilagine ialina, elastica e fibrosa.
L’ECM della cartilagine che riveste le articolazioni, la cartilagine ialina (che in seno a queste funge da rivestimento per i capi articolari e lubrifica e ammortizza, ndr), è formata da matrice amorfa e da fibre di collagene di tipo II, IX e XI, ma non collagene I, caratteristico dei tessuti connettivi fibrosi e della fibrocartilagine. Non essendo vascolarizzate, le cartilagini hanno una capacità rigenerativa quasi nulla.
Nel contesto di questo tessuto, il trattamento di questo tipo di lesioni rappresenta una sfida importante per pazienti e, soprattuto, ricercatori. Nei giovani, le lesioni sono dovute per lo più a traumi, difetti posturali e squilibri osteo-muscolari; nei soggetti più anziani prevalgono problematiche degenerative come l’artrosi e l’artrite reumatoide. In base all’entità del danno possono presentarsi generalmente con dolore, tumefazione e limitazioni dei movimenti.
Quali, dunque, le soluzioni alle lesioni della cartilagine?
Sono diversi i trattamenti utili, farmacologici e chirurgici, con indicazioni diverse in base al tipo di lesione e di paziente.
Nell’ambito dei trattamenti chirurgici rigenerativi è stato recentemente fatto un passo avanti, che potrebbe rivelarsi assai promettente e potrebbe altresì risolvere molte delle problematiche legate alle attuali strategie chirurgiche, come la mosaicoplastica (innesto autologo osteocondrale) e l’innesto di condrociti autologhi (tecniche ACI-MACI).
In particolare, un gruppo del Centro di Ricerca e Applicazione sulle cellule hiPS (staminali pluripotenti indotte umane, ndr) dell’Università di Kyoto, guidato dal Dr. Tsumaki, ha sviluppato un nuovo protocollo per la produzione di cartilagini a partire dalle iPS-cell.
Questo consiste nell’espansione di cellule staminali, nel loro differenziano in condrociti dopo il raggiungimento di un sufficiente numero di cellule e la successiva correzione del medium di coltura contente BMP2, TGF-b e GDF5: questo metodo permette di ottenere una cartilagine ialina esattamente come l’originale, in cui sono presenti cioè collagene di tipo II e XI ma non di tipo I.
La tecnica proposta dallo studio si propone come potenziale sostituta degli attuali trattamenti terapeutici che, per quanto vantaggiosi, risultano ancora al quanto traumatici.
Nel caso della mosaicoplastica vi è il prelievo di “cilindri osteocondriali” da un’articolazione, o parte di essa, poco sollecitata e l’innesto nella sede della lesione. Con le metodiche ACI-MACI il paziente viene sottoposto a due interventi nell’arco di uno o due mesi: una biopsia per reperire dei condrociti ed un intervento complesso non eseguibile in artroscopia per correggere il difetto cartilagineo.
In ogni caso non vi sarebbe il bisogno di scendere a compromessi sacrificando parte di una cartilagine buona per riparare la zona danneggiata di un’altra. L’espansione in coltura dei condrociti, infatti, necessita di una preventiva digestione della ECM, operazione che comporta il differenziamento di alcuni condrociti in fibroblasti e la formazione di una cartilagine funzionalmente peggiore, a causa della consistente quantità di collegare di tipo I prodotta da questi ultimi.
Col nuovo protocollo hiPS si produrrebbe una cartilagine migliore e senza l’uso di scaffold (supporto, ndr) alle cellule (quest’ultimo era stato introdotto nella MACI per ovviare a vari problemi, come la crescita incontrollata e in monostrati dei condrociti, “difetto” che si riscontrava con la tecnica ACI, ndr).
Dopo aver sviluppato questo protocollo, i ricercatori hanno eseguito i primi test su animali: hanno impiantato le particelle di cartilagine prodotta nel sottocute di alcuni topi SCID (Severe combined immunodeficiency), a livello articolare di altri topi, ratti e maialini nani. I risultati ottenuti hanno mostrato un’ottima integrazione tra il tessuto impiantato e quello circostante, senza alcun segno di teratogenesi.
Sono stati ottenuti, quindi, risultati molto incoraggianti che, se verranno confermati da ulteriori sperimentazioni su animali di maggiori dimensioni e da test sulla sicurezza, porteranno alla sperimentazione sull’uomo e, probabilmente, a una notevole innovazione nella terapia delle condropatie.
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