Engineering Human Stellate Cells For Beta Cell Replacement Therapy Promotes In Vivo Recruitment Of Regulatory T Cells
| Autor: | Fusun Can, Tugba Bal, Yasemin Inceoglu, Mukrime Birgul Akolpoglu, Tugba Bagci-Onder, Dilem Ceren Oran, Seda Kizilel, Metin Kurtoglu, O. Albayrak, Mert Erkan, Tolga Lokumcu |
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| Přispěvatelé: | Oran, Dilem Ceren, Lokumcu, Tolga, Bal, Tuǧba, İnceoğlu, Yasemin, Albayrak, Özgür, Erkan, Mert M., Kurtoglu, Metin, Can, Füsun (ORCID 0000-0001-9387-2526 & YÖK ID 103165), Önder, Tuğba Bağcı (ORCID 0000-0003-3646-2613 & YÖK ID 184359), Kızılel, Seda (ORCID 0000-0001-9092-2698 & YÖK ID 28376), Akolpoğlu, Mükrime Birgül, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), Graduate School of Sciences and Engineering, Graduate School of Health Sciences, College of Engineering, School of Medicine, Department of Biomedical Sciences and Engineering, Department of Chemical and Biological Engineering |
| Rok vydání: | 2019 |
| Předmět: |
Chemokine
endocrine system Regulatory T cell Biomedical Engineering Bioengineering Immune tolerance Biomaterials Immune system medicine Molecular Biology Immunologic Tolerance lcsh:QH301-705.5 lcsh:R5-920 biology business.industry Biomedical sciences Cell Biology Transplantation medicine.anatomical_structure lcsh:Biology (General) Hepatic stellate cell biology.protein Cancer research CCL22 Immune engineering Islet transplantation Regulatory T cells Stellate cells Beta cell business lcsh:Medicine (General) Biotechnology |
| Zdroj: | Materials Today Bio, Vol 2, Iss, Pp-(2019) Materials Today Bio |
| Popis: | Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients’ own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance. Scientific and Technological Research Council of Turkey (TÜBİTAK) |
| Databáze: | OpenAIRE |
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