Assessment of Cardiosphere-Derived Cell Exosomes as Possible Modulator of Alloimmunity in a Mouse Model of HLA-A2 Allosensitization.
1Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
2Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
Meeting: 2017 American Transplant Congress
Abstract number: B43
Keywords: Alloantibodies, B cells
Session Information
Session Name: Poster Session B: Allorecognition and T Cell Biology
Session Type: Poster Session
Date: Sunday, April 30, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Purpose: Mounting data indicate that exosomes, a nanosized membrane particle secreted by cells has immune regulatory properties, including anti-inflammation and mediating autocrine, paracrine, and endocrine functions. Donor specific antibody (DSA) responses are major hurdle in successful organ transplantation. Therefore, medications to prevent alloantibodies from production by B cells are critical component in antirejection therapy. Here we examined the ability of cardiac exosomes to modify alloimmune responses in a mouse model of allosensitization.
Methods: We utilized an established mouse model of HLA.A2 sensitization using a C57BL/6 mouse recipient of a skin graft (SG) from a C57BL/6-tg-HLA.A2 mouse (donor). Three (3) treatment groups were studied. Group 1: intraperitoneal (IP) injection of cardiac sphere-derived exosome (50ul/injection daily for 14 days). Group 2: intradermal (ID) administration of exosome (single injection of 100ul exosome into skin graft tissue immediately following transplantation). Group 3: medium control (exosome medium 50ul/injection daily for 14 days). Blood samples are drawn weekly for monitoring DSA titers using a flow cytometric antibody binding assay.
Results: All 3 groups exhibited similar rejection scores at day 6 post-transplantation, indicating that exosome had no impact on skin graft survival. Intradermal injection of exosome into skin graft tissue immediately after transplantation, however, had a suppressive effect on DSA IgG production. DSA IgG levels were significantly reduced at days 14 (117+77 MFI vs. control 299+75MFI, p=0.0015), 21 (269+98 MFI vs. control 385+16MFI, p=0.0072), and 28 (245+88MFI vs. control 368+39MFI, p=0.014) . Intraperitoneal injection of exosome did not reduce DSA IgG levels.
Conclusion: IP injections of cardiac sphere -derived exosomes had no impact on DSA generation. However, intra-dermal injections of cardiac sphere -derived exosomes did result in significant suppression of DSA generation, suggestion that the exosomes may interfere with APC activity in the graft, reducing immune stimulation to the hosts' immune system.
CITATION INFORMATION: Kim I, Wu G, Chai N.-N, De Couto G, Marban E, Klein A, Jordan S. Assessment of Cardiosphere-Derived Cell Exosomes as Possible Modulator of Alloimmunity in a Mouse Model of HLA-A2 Allosensitization. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Kim I, Wu G, Chai N-N, Couto GDe, Marban E, Klein A, Jordan S. Assessment of Cardiosphere-Derived Cell Exosomes as Possible Modulator of Alloimmunity in a Mouse Model of HLA-A2 Allosensitization. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/assessment-of-cardiosphere-derived-cell-exosomes-as-possible-modulator-of-alloimmunity-in-a-mouse-model-of-hla-a2-allosensitization/. Accessed May 9, 2025.« Back to 2017 American Transplant Congress