Noninvasive Monitoring of Allogeneic Stem Cell Delivery with Dual-Modality Imaging-Visible Microcapsules in a Rabbit Model of Peripheral Arterial Disease Journal Article

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Authors: Fu, Y; Weiss, C. R.; Kedziorek, D. A.; Xie, Y.; Tully, E.; Shea, S. M.; Solaiyappan, M.; Ehtiati, T.; Gabrielson, K.; Wacker, F. H.; Bulte, J. W. M.; Kraitchman, D. L.
Article Title: Noninvasive Monitoring of Allogeneic Stem Cell Delivery with Dual-Modality Imaging-Visible Microcapsules in a Rabbit Model of Peripheral Arterial Disease
Abstract: Stem cell therapies, although promising for treating peripheral arterial disease (PAD), often suffer from low engraftment rates and the inability to confirm the delivery success and track cell distribution and engraftment. Stem cell microencapsulation combined with imaging contrast agents may provide a means to simultaneously enhance cell survival and enable cell tracking with noninvasive imaging. Here, we have evaluated a novel MRI- and X-ray-visible microcapsule formulation for allogeneic mesenchymal stem cell (MSC) delivery and tracking in a large animal model. Bone marrow-derived MSCs from male New Zealand White rabbits were encapsulated using a modified cell encapsulation method to incorporate a dual-modality imaging contrast agent, perfluorooctyl bromide (PFOB). PFOB microcapsules (PFOBCaps) were then transplanted into the medial thigh of normal or PAD female rabbits. In vitro MSC viability remained high (79 +/- 5% at 4 weeks of postencapsulation), and as few as two and ten PFOBCaps could be detected in phantoms using clinical C-arm CT and (19)F MRI, respectively. Successful injections of PFOBCaps in the medial thigh of normal (n = 15) and PAD (n = 16) rabbits were demonstrated on C-arm CT at 1-14 days of postinjection. Using (19)F MRI, transplanted PFOBCaps were clearly identified as "hot spots" and showed one-to-one correspondence to the radiopacities on C-arm CT. Concordance of (19)F MRI and C-arm CT locations of PFOBCaps with postmortem locations was high (95%). Immunohistological analysis revealed high MSC survival in PFOBCaps (>56%) two weeks after transplantation while naked MSCs were no longer viable beyond three days after delivery. These findings demonstrate that PFOBCaps could maintain cell viability even in the ischemic tissue and provide a means to monitor cell delivery and track engraftment using clinical noninvasive imaging systems.
Journal Title: Stem cells international
Volume: 2019
ISSN: 1687-966X
Publisher: Unknown  
Journal Place: United States
Date Published: 2019
Start Page: 9732319
Language: eng
DOI/URL:

10.1155/2019/9732319
Notes: LR: 20190422; GR: R01 HL073223/HL/NHLBI NIH HHS/United States; GR: R21 HL089029/HL/NHLBI NIH HHS/United States; GR: R33 HL089029/HL/NHLBI NIH HHS/United States; JID: 101535822; 2018/10/30 00:00 [received]; 2019/01/06 00:00 [revised]; 2019/01/28 00:00 [accepted]; 2019/04/20 06:00 [entrez]; 2019/04/20 06:00 [pubmed]; 2019/04/20 06:01 [medline]; epublish