Noninvasive monitoring of allogeneic stem cell delivery with dual-modality imaging-visible microcapsules in a rabbit model of peripheral arterial disease

Yingli Fu, Clifford Weiss, Dorota Kedziorek, Yibin Xie, Ellen Tully, Steven M. Shea, Meiyappan Solaiyappan, Tina Ehtiati, Kathleen L Gabrielson, Frank H. Wacker, Jeff W Bulte, Dara Kraitchman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number9732319
JournalStem Cells International
Volume2019
DOIs
StatePublished - Jan 1 2019

Fingerprint

Peripheral Arterial Disease
Capsules
Stem Cells
Rabbits
Cell Survival
Arm
Mesenchymal Stromal Cells
Cell Tracking
Thigh
Contrast Media
Drug Compounding
perflubron
Cell- and Tissue-Based Therapy
Animal Models
Transplantation
Bone Marrow
X-Rays
Injections

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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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.",
author = "Yingli Fu and Clifford Weiss and Dorota Kedziorek and Yibin Xie and Ellen Tully and Shea, {Steven M.} and Meiyappan Solaiyappan and Tina Ehtiati and Gabrielson, {Kathleen L} and Wacker, {Frank H.} and Bulte, {Jeff W} and Dara Kraitchman",
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language = "English (US)",
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T1 - Noninvasive monitoring of allogeneic stem cell delivery with dual-modality imaging-visible microcapsules in a rabbit model of peripheral arterial disease

AU - Fu, Yingli

AU - Weiss, Clifford

AU - Kedziorek, Dorota

AU - Xie, Yibin

AU - Tully, Ellen

AU - Shea, Steven M.

AU - Solaiyappan, Meiyappan

AU - Ehtiati, Tina

AU - Gabrielson, Kathleen L

AU - Wacker, Frank H.

AU - Bulte, Jeff W

AU - Kraitchman, Dara

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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