Immunogenicity of induced pluripotent stem cell-derived smooth muscle cells results from a reduction in the expression of indoleamine 2,3 dioxygenase (IDO-1).
Katherine Partridge, Vera J Mehler, Chris J Burns, Jordan S Pober, Melanie L Moore
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引用次数: 0
Abstract
Background: Smooth muscle cells (SMCs) derived from allogeneic induced pluripotent stem cells (iPSC) hold significant potential in cellular therapy for many cardiovascular diseases. However, their immunological profile is poorly characterized, limiting their clinical progression.
Aims: This study aimed to investigate the immunogenicity of iPSC-SMC in comparison with naturally derived vascular SMCs (v-SMCs).
Result: We found iPSC-SMCs, in contrast to naturally derived vascular SMCs (v-SMC), triggered T effector memory (TEM) cell proliferation. However, expression of TEM activation-related proteins was comparable between both cell types. Since arterial v-SMCs can also establish immunoprivilege through indoleamine 2,3 dioxygenase (IDO-1) activity, we therefore investigated IDO-1 expression in two independently engineered iPSC-SMCs (NIBSC 8 (N8) and Yale 6 (Y6)). IDO-1 expression and functionality was markedly reduced in both iPSC-SMC lines compared to v-SMC and unlike v-SMC, neither iPSC-SMC line could modulate the immune response in a co-culture with CD3/CD28 activated peripheral blood mononuclear cells (PBMC).
Conclusions: These results indicate that iPSC-SMC's impaired ability to modulate the immune response through IDO-1 expression contributes to their differing immunogenicity to v-SMC and highlights the importance of immune phenotyping for therapeutic applications of iPSC-derivatives.
期刊介绍：
Regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function*. Since 2006, Regenerative Medicine has been at the forefront of publishing the very best papers and reviews covering the entire regenerative medicine sector. The journal focusses on the entire spectrum of approaches to regenerative medicine, including small molecule drugs, biologics, biomaterials and tissue engineering, and cell and gene therapies – it’s all about regeneration and not a specific platform technology. The journal’s scope encompasses all aspects of the sector ranging from discovery research, through to clinical development, through to commercialization. Regenerative Medicine uniquely supports this important area of biomedical science and healthcare by providing a peer-reviewed journal totally committed to publishing the very best regenerative medicine research, clinical translation and commercialization.
Regenerative Medicine provides a specialist forum to address the important challenges and advances in regenerative medicine, delivering this essential information in concise, clear and attractive article formats – vital to a rapidly growing, multidisciplinary and increasingly time-constrained community.
Despite substantial developments in our knowledge and understanding of regeneration, the field is still in its infancy. However, progress is accelerating. The next few decades will see the discovery and development of transformative therapies for patients, and in some cases, even cures. Regenerative Medicine will continue to provide a critical overview of these advances as they progress, undergo clinical trials, and eventually become mainstream medicine.
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