Short-term function and immune-protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non-human primates without systemic immune suppression: A pilot study.

التفاصيل البيبلوغرافية
العنوان:	Short-term function and immune-protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non-human primates without systemic immune suppression: A pilot study.
المؤلفون:	Sremac M; Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Luo H; Division of Transplant Surgery and Center of Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of General Surgery, General Hospital of Western Theater Command, Chengdu, China., Deng H; Division of Transplant Surgery and Center of Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA., Parr MFE; Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Hutcheson J; ViCapsys, Inc., Athens, Georgia, USA., Verde PS; Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Alagpulinsa DA; Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Kitzmann JM; Department of Surgery, Institute for Cellular Transplantation, University of Arizona, Tucson, Arizona, USA., Papas KK; Department of Surgery, Institute for Cellular Transplantation, University of Arizona, Tucson, Arizona, USA., Brauns T; Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Markmann JF; Division of Transplant Surgery and Center of Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA., Lei J; Division of Transplant Surgery and Center of Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA., Poznansky MC; Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
المصدر:	Xenotransplantation [Xenotransplantation] 2023 Nov-Dec; Vol. 30 (6), pp. e12826. Date of Electronic Publication: 2023 Sep 15.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Munksgaard International Publishers Country of Publication: Denmark NLM ID: 9438793 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-3089 (Electronic) Linking ISSN: 0908665X NLM ISO Abbreviation: Xenotransplantation Subsets: MEDLINE
أسماء مطبوعة:	Publication: Copenhagen : Munksgaard International Publishers Original Publication: Copenhagen : Munksgaard, c1994-
مواضيع طبية MeSH:	Diabetes Mellitus* , Islets of Langerhans* , Islets of Langerhans Transplantation*/methods, Animals ; Alginates ; Chemokine CXCL12 ; Graft Survival ; Immunosuppression Therapy/methods ; Pilot Projects ; Primates ; Swine ; Transplantation, Heterologous/methods
مستخلص:	Replacement of insulin-producing pancreatic beta-cells by islet transplantation offers a functional cure for type-1 diabetes (T1D). We recently demonstrated that a clinical grade alginate micro-encapsulant incorporating the immune-repellent chemokine and pro-survival factor CXCL12 could protect and sustain the integrity and function of autologous islets in healthy non-human primates (NHPs) without systemic immune suppression. In this pilot study, we examined the impact of the CXCL12 micro encapsulant on the function and inflammatory and immune responses of xenogeneic islets transplanted into the omental tissue bilayer sac (OB; n = 4) and diabetic (n = 1) NHPs. Changes in the expression of cytokines after implantation were limited to 2-6-fold changes in blood, most of which did not persist over the first 4 weeks after implantation. Flow cytometry of PBMCs following transplantation showed minimal changes in IFNγ or TNFα expression on xenoantigen-specific CD4 ⁺ or CD8 ⁺ T cells compared to unstimulated cells, and these occurred mainly in the first 4 weeks. Microbeads were readily retrievable for assessment at day 90 and day 180 and at retrieval were without microscopic signs of degradation or foreign body responses (FBR). In vitro and immunohistochemistry studies of explanted microbeads indicated the presence of functional xenogeneic islets at day 30 post transplantation in all biopsied NHPs. These results from a small pilot study revealed that CXCL12-microencapsulated xenogeneic islets abrogate inflammatory and adaptive immune responses to the xenograft. This work paves the way toward future larger scale studies of the transplantation of alginate microbeads with CXCL12 and porcine or human stem cell-derived beta cells or allogeneic islets into diabetic NHPs without systemic immunosuppression. (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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معلومات مُعتمدة:	grant 2-SRA-2014-290-Q-R United States JDRF
فهرسة مساهمة:	Keywords: alginate; chemokine CXCL12; immunosuppression; microencapsulated; porcine islets
المشرفين على المادة:	0 (Alginates) 0 (Chemokine CXCL12)
تواريخ الأحداث:	Date Created: 20230915 Date Completed: 20231223 Latest Revision: 20231223
رمز التحديث:	20231223
DOI:	10.1111/xen.12826
PMID:	37712342
قاعدة البيانات:	MEDLINE

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تدمد:	1399-3089
DOI:	10.1111/xen.12826