Associate Professor University College London (UCL) London, England, United Kingdom
Abstract: Stem cell-derived therapies represent a cutting-edge frontier in regenerative medicine, offering innovative solutions for complex degenerative diseases by replacing damaged or diseased tissues with healthy cells. While significant progress has been made, ensuring the safety and efficacy of these therapies remains paramount. Critical considerations include teratoma risk, traceability, and genetic stability of pluripotent stem cell lines. Recent efforts have focused on understanding chromosomal abnormalities and functional alterations that could influence cell behaviour, survival, and proliferation. Despite these advancements, the impact of the genetic background of pluripotent stem cells on their therapeutic potential, including predisposition to the diseases they aim to treat, remains poorly understood.
Here we have sequenced genetic risk scores for AMD in induced pluripotent stem cells from patients with neovascular AMD and clinical grade human embryonic stem cell lines, including ones currently being used as cell therapy clinical trials for AMD. All cell lines contained at least one risk allele for AMD, and various combinations of alleles associated with increased/decreased predisposition to AMD. Genetic risk scores, calculated for each cell line, ranged from 0.59-0.84, suggesting all lines examined have genetic backgrounds associated with increased risk of AMD.
The impact of transplanting stem cell-derived therapies with a genetic predisposition to AMD into a compromised disease environment is unknown. The genetic background could influence donor cell viability, functionality, and therapeutic efficacy. Investigating how specific genetic variations affect stem cell-derived RPE will be crucial for guiding future research and optimising effective treatment strategies for AMD.
Funding Source: The London Project To Cure Blindness
