Advances in Production of Retinal Cells for Treating Blindness / Progressi nella produzione di cellule retiniche per il trattamento della cecità
Advances in Production of Retinal Cells for Treating Blindness / Progressi nella produzione di cellule retiniche per il trattamento della cecità
Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa
Researchers at Karolinska Institutet and St Erik Eye Hospital in Sweden have discovered a way to refine the production of retinal cells from embryonic stem cells for treating blindness in the elderly. Using the CRISPR/Cas9 gene editing, they have also managed to modify the cells so that they can hide from the immune system to prevent rejection. The studies are published in the scientific journals Nature Communications and Stem Cell Reports.
Age-related macular degeneration of the eye is the most common cause of blindness in the elderly. This loss of vision is caused by the death of the photoreceptors (the rods and cones) resulting from the degeneration and death of the underlying retinal pigment epithelial (RPE cells), which provide the rods and cones vital nourishment. A possible future treatment could be to transplant fresh RPE cells formed from embryonic stem cells.
Working with colleagues at St Erik Eye Hospital, researchers at Karolinska Institutet have now found specific markers on the surface of the RPE cells that can be used to isolate and purify these retinal cells. The results are published in Nature Communications.
"The finding has enabled us to develop a robust protocol that ensures that the differentiation of embryonic stem cells into RPE cells is effective and that there is no contamination of other cell types," says principal investigator Fredrik Lanner, researcher at the Department of Clinical Science, Intervention and Technology and the Ming Wai Lau Center for Reparative Medicine at Karolinska Institutet. "We've now begun the production of RPE cells in accordance with our new protocol for the first clinical study, which is planned for the coming years."
One obstacle when transplanting tissue generated from stem cells is the risk of rejection, which occurs if transplantation antigens of the donor and patient tissue differ. Research groups around the world are therefore working on creating what are known as universal cells, which ideally will not trigger an immune response.
In a study published in Stem Cell Reports the same group at Karolinska Institutet created embryonic stem cells able to hide from the immune system. Using CRISPR/Cas9 gene editing, they removed certain molecules, HLA class I and class II, which sit on the surface of the stem cells as a means by which the immune system can identify them as endogenous or not. The stem cells lacking these molecules were then differentiated into RPE cells.
The researchers have been able to show that the modified RPE cells retain their character, that no harmful mutations appear in the process and that the cells can avoid the immune system's T cells without activating other immune cells. The rejection response was also significantly less and more delayed than after the transplantation of regular RPE cells, the surfaces of which still possess HLA molecules.
"The research is still in an early stage, but this can be an important initial step towards creating universal RPE cells for the future treatment of age-related macular degeneration," says joint last author Anders Kvanta, adjunct professor at the Department of Clinical Neuroscience and consultant at St Erik Eye Hospital.
Age-related macular degeneration of the eye is the most common cause of blindness in the elderly. This loss of vision is caused by the death of the photoreceptors (the rods and cones) resulting from the degeneration and death of the underlying retinal pigment epithelial (RPE cells), which provide the rods and cones vital nourishment. A possible future treatment could be to transplant fresh RPE cells formed from embryonic stem cells.
Working with colleagues at St Erik Eye Hospital, researchers at Karolinska Institutet have now found specific markers on the surface of the RPE cells that can be used to isolate and purify these retinal cells. The results are published in Nature Communications.
"The finding has enabled us to develop a robust protocol that ensures that the differentiation of embryonic stem cells into RPE cells is effective and that there is no contamination of other cell types," says principal investigator Fredrik Lanner, researcher at the Department of Clinical Science, Intervention and Technology and the Ming Wai Lau Center for Reparative Medicine at Karolinska Institutet. "We've now begun the production of RPE cells in accordance with our new protocol for the first clinical study, which is planned for the coming years."
One obstacle when transplanting tissue generated from stem cells is the risk of rejection, which occurs if transplantation antigens of the donor and patient tissue differ. Research groups around the world are therefore working on creating what are known as universal cells, which ideally will not trigger an immune response.
In a study published in Stem Cell Reports the same group at Karolinska Institutet created embryonic stem cells able to hide from the immune system. Using CRISPR/Cas9 gene editing, they removed certain molecules, HLA class I and class II, which sit on the surface of the stem cells as a means by which the immune system can identify them as endogenous or not. The stem cells lacking these molecules were then differentiated into RPE cells.
The researchers have been able to show that the modified RPE cells retain their character, that no harmful mutations appear in the process and that the cells can avoid the immune system's T cells without activating other immune cells. The rejection response was also significantly less and more delayed than after the transplantation of regular RPE cells, the surfaces of which still possess HLA molecules.
"The research is still in an early stage, but this can be an important initial step towards creating universal RPE cells for the future treatment of age-related macular degeneration," says joint last author Anders Kvanta, adjunct professor at the Department of Clinical Neuroscience and consultant at St Erik Eye Hospital.
ITALIANO
I ricercatori del Karolinska Institutet e del St Erik Eye Hospital in Svezia hanno scoperto un modo per affinare la produzione di cellule retiniche dalle cellule staminali embrionali per il trattamento della cecità negli anziani. Utilizzando l'editing genico CRISPR / Cas9, sono anche riusciti a modificare le cellule in modo che possano nascondersi dal sistema immunitario per prevenire il rigetto. Gli studi sono pubblicati nelle riviste scientifiche Nature Communications e Stem Cell Reports.
La degenerazione maculare legata all'età è la causa più comune di cecità negli anziani. Questa perdita della vista è causata dalla morte dei fotorecettori (i bastoncelli e i coni) risultanti dalla degenerazione e morte del sottostante epiteliale del pigmento retinico (cellule RPE), che forniscono ai bastocellie e ai coni un nutrimento vitale. Un possibile trattamento futuro potrebbe essere il trapianto di cellule RPE fresche formate da cellule staminali embrionali.
In collaborazione con i colleghi dell'ospedale oculistico di St Erik, i ricercatori del Karolinska Institutet hanno ora trovato marcatori specifici sulla superficie delle cellule RPE che possono essere utilizzati per isolare e purificare queste cellule retiniche. I risultati sono pubblicati su Nature Communications.
"La scoperta ci ha permesso di sviluppare un protocollo solido che garantisce che la differenziazione delle cellule staminali embrionali in cellule RPE sia efficace e che non vi siano contaminazioni di altri tipi di cellule", afferma il ricercatore principale Fredrik Lanner, ricercatore presso il Dipartimento di Scienze cliniche , Intervention and Technology e Ming Wai Lau Center for Reparative Medicine presso Karolinska Institutet. "Ora abbiamo iniziato la produzione di cellule RPE in conformità con il nostro nuovo protocollo per il primo studio clinico, che è previsto per i prossimi anni".
Un ostacolo durante il trapianto di tessuto generato da cellule staminali è il rischio di rigetto, che si verifica se gli antigeni del trapianto del donatore e del tessuto del paziente differiscono. I gruppi di ricerca di tutto il mondo stanno quindi lavorando per creare quelle che sono note come cellule universali, che idealmente non innescheranno una risposta immunitaria.
In uno studio pubblicato su Stem Cell Reports, lo stesso gruppo del Karolinska Institutet ha creato cellule staminali embrionali in grado di nascondersi dal sistema immunitario. Usando la modifica del gene CRISPR / Cas9, hanno rimosso alcune molecole, HLA di classe I e classe II, che si trovano sulla superficie delle cellule staminali come mezzo attraverso il quale il sistema immunitario può identificarle come endogene o no. Le cellule staminali prive di queste molecole sono state quindi differenziate in cellule RPE.
I ricercatori sono stati in grado di dimostrare che le cellule RPE modificate mantengono il loro carattere, che non appaiono mutazioni dannose nel processo e che le cellule possono evitare le cellule T del sistema immunitario senza attivare altre cellule immunitarie. La risposta al rigetto è stata anche significativamente minore e più ritardata rispetto al trapianto di normali cellule RPE, le cui superfici possiedono ancora molecole HLA.
"La ricerca è ancora in una fase iniziale, ma questo può essere un importante passo iniziale verso la creazione di cellule RPE universali per il futuro trattamento della degenerazione maculare legata all'età", afferma l'ultimo autore congiunto Anders Kvanta, professore aggiunto presso il Dipartimento di Neuroscienze cliniche e consulente all'ospedale st Erik Eye.
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