التفاصيل البيبلوغرافية
| العنوان: |
Abstract 193: CRISPR-mediated Introduction of the Sodium-iodide Symporter to Enable Non-invasive Monitoring of Macaque Induced-pluripotent Stem Cell-derived Cardiomyocytes |
| المؤلفون: |
Ostrominski, John, Yada, Ravi Chandra, Sato, Noriko, Palisoc, Maryknoll, Pittaluga, Stefania, Lin, Yongshun, Zou, Jizhong, Peng, Kah-Whye, Hong, So Gun, Dunbar, Cynthia |
| المصدر: |
Circulation Research ; volume 121, issue suppl_1 ; ISSN 0009-7330 1524-4571 |
| بيانات النشر: |
Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: |
2017 |
| الوصف: |
Due to the limited regenerative capacity of mature cardiomyocytes, cardiac cell therapies constitute an exciting strategy for myocardial repair. However, there is limited understanding of the spatio-temporal distribution and survival of transplanted cells. Hence, there is demand for technologies enabling long-term non-invasive tracking of transplanted cellular therapeutics. Sodium-iodide symporter (NIS)-based in vivo imaging has many potential advantages, including predicted safety and immunotolerance due to reliance on an endogenous species-specific gene and on widely available imaging technologies. We believe that non-human primates represent ideal models for investigating the biology of allogenic or autologous cellular grafts, because of close physiologic similarity to humans. We report the development of NIS-based in vivo imaging to detect and track rhesus induced pluripotent stem cell (RhiPSC)-derived teratomas as a proof-of-concept model tested in mice, and characterization of NIS-positive RhiPSC (NIS-RhiPSC)-derived cardiomyocytes (CM). NIS-RhiPSCs were generated by CRISPR/Cas9-mediated integration of the rhesus NIS cDNA within the AAVS1 safe harbor locus. NIS was stably expressed and radiotracer uptake by NIS-RhiPSCs was demonstrated in vitro . To evaluate viability of NIS-mediated imaging in RhiPSCs, undifferentiated NIS-RhiPSCs were introduced intramuscularly into immunodeficient mice, and NIS imaging was performed via PET/CT at 2, 4, and 6-weeks post-injection. NIS-positive teratomas were readily detectable as early as 2 weeks post-injection, prior to development of any palpable mass. Using our previously established differentiation protocol, NIS-RhiPS-CMs were derived with high purity, exhibited spontaneous beating in culture, and were similar in all aspects to parental RhiPS-CMs. NIS-RhiPS-CMs maintained stable NIS expression that was comparable to undifferentiated NIS-RhiPSCs, suggesting that in vivo imaging of transplanted NIS-RhiPS-CMs should be feasible. Further functional characterization of ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1161/res.121.suppl_1.193 |
| الإتاحة: |
https://doi.org/10.1161/res.121.suppl_1.193Test |
| رقم الانضمام: |
edsbas.361315CB |
| قاعدة البيانات: |
BASE |
