The capsule was never just a capsule: what islet encapsulation is for, now that immunoisolation is no longer its job.
- 1Diabetes Research Institute (DRI), IRCCS Ospedale San Raffaele, Milan, Italy.
- 2Università Vita-Salute San Raffaele, Milan, Italy.
Abstract
For more than four decades, islet encapsulation has been defined by a single objective: to immunoprotect transplanted cells while preserving glucose sensing and insulin delivery, thereby eliminating systemic immunosuppression. No passive device has yet achieved that objective with reproducible, durable and clinically meaningful efficacy. The central limitation is not simply the absence of an optimal polymer, but an over-constrained architecture in which immune exclusion, molecular transport, therapeutic cell dose, host integration, mechanical durability and retrieval must be solved simultaneously. The clinical contrast between sealed and vascularly accessible devices makes this coupling visible: closure preserves immunological separation but intensifies transport and foreign-body constraints; opening improves tissue integration but restores immune access. Hypoimmune cell engineering now changes the allocation of these functions. Gene-edited allogeneic islet cells have survived without a capsule or systemic immunosuppression in immunocompetent primates and, to date, in one human recipient from a single programme, although therapeutic sufficiency, scalability, independent replication and long-term safety remain unresolved. We argue that this development should not make encapsulation obsolete, but should redefine its target product profile. When immune protection is increasingly engineered into the cell product, the device can be optimised for the functions that remain uniquely physical: containment, vascular integration, complete retrievability and layered safety. This shifts the biomaterials problem from molecular immunoisolation to a low-transport-resistance, defect-controlled and mechanically durable containment platform for proliferative, immune-evasive cell therapies.
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BibTeX
@article{citro2026capsule,
title = {{The capsule was never just a capsule: what islet encapsulation is for, now that immunoisolation is no longer its job.}},
author = {Antonio Citro and Lorenzo Piemonti},
journal = {Frontiers in bioengineering and biotechnology},
year = {2026},
month = oct,
doi = {10.3389/fbioe.2026.1943061},
url = {https://europepmc.org/article/MED/42923301},
note = {CC BY},
}
RIS
TY - JOUR
TI - The capsule was never just a capsule: what islet encapsulation is for, now that immunoisolation is no longer its job.
AU - Antonio Citro
AU - Lorenzo Piemonti
PY - 2026
DA - 2026/10/08
JO - Frontiers in bioengineering and biotechnology
DO - 10.3389/fbioe.2026.1943061
UR - https://europepmc.org/article/MED/42923301
AB - For more than four decades, islet encapsulation has been defined by a single objective: to immunoprotect transplanted cells while preserving glucose sensing and insulin delivery, thereby eliminating systemic immunosuppression. No passive device has yet achieved that objective with reproducible, durable and clinically meaningful efficacy. The central limitation is not simply the absence of an optimal polymer, but an over-constrained architecture in which immune exclusion, molecular transport, therapeutic cell dose, host integration, mechanical durability and retrieval must be solved simultaneously. The clinical contrast between sealed and vascularly accessible devices makes this coupling visible: closure preserves immunological separation but intensifies transport and foreign-body constraints; opening improves tissue integration but restores immune access. Hypoimmune cell engineering now changes the allocation of these functions. Gene-edited allogeneic islet cells have survived without a capsule or systemic immunosuppression in immunocompetent primates and, to date, in one human recipient from a single programme, although therapeutic sufficiency, scalability, independent replication and long-term safety remain unresolved. We argue that this development should not make encapsulation obsolete, but should redefine its target product profile. When immune protection is increasingly engineered into the cell product, the device can be optimised for the functions that remain uniquely physical: containment, vascular integration, complete retrievability and layered safety. This shifts the biomaterials problem from molecular immunoisolation to a low-transport-resistance, defect-controlled and mechanically durable containment platform for proliferative, immune-evasive cell therapies.
SN - 2296-4185
ER -