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Quantitative CT and 19F-MRI tracking of perfluorinated encapsulated mesenchymal stem cells to assess graft immunorejection

  • Guan Wang
  • Yingli Fu
  • Steven M. Shea
  • Shashank Sathyanarayana Hegde
  • Dara L. KraitchmanEmail author
Research Article

Abstract

Objectives

Peripheral artery disease (PAD) affects 12–14% of the world population, and many are not eligible for conventional treatment. For these patients, microencapsulated stem cells (SCs) offer a novel means to transplant mismatched therapeutic SCs to prevent graft immunorejection. Using c-arm CT and 19F-MRI for serial evaluation of dual X-ray/MR-visible SC microcapsules (XMRCaps) in a non-immunosuppressed rabbit PAD model, we explore quantitative evaluation of capsule integrity as a surrogate of transplanted cell fate.

Materials and methods

XMRCaps were produced by impregnating 12% perfluorooctylbromine (PFOB) with rabbit or human SCs (AlloSC and XenoSC, respectively). Volume and 19F concentration measurements of XMRCaps were assessed both in phantoms and in vivo, at days 1, 8 and 15 after intramuscular administration in rabbits (n = 10), by 3D segmenting the injection sites and referencing to standards with known concentrations.

Results

XMRCap volumes and concentrations showed good agreement between CT and MRI both in vitro and in vivo in XenoSC rabbits. Injected capsules showed small variations over time and were similar between AlloSC and XenoSC rabbits. Histological staining revealed high cell viability and intact capsules 2 weeks after administration.

Conclusions

Quantitative and non-invasive tracking XMRCaps using CT and 19F-MRI may be useful to assess graft immunorejection after SC transplantation.

Keywords

Quantitative tracking 19F-MRI Encapsulated stem cells Peripheral artery disease Immunorejection 

Abbreviations

19F-MRI

Fluorine magnetic resonance imaging

Allo

Allogeneic

ANOVA

Analysis of variance

bSSFP

Balanced steady-state free precession

DSA

Digital subtraction angiogram

FOV

Field of view

H&E

Hematoxylin and eosin

HU

Hounsfield units

HuNa

Anti-human nuclear antigen

MIP

Maximum intensity projection

MSCs

Mesenchymal stem cells

PAD

Peripheral artery disease

PFOB

Perfluorooctylbromide

ROI

Region of interest

SC

Stem cell

SFA

Superficial femoral artery

TE

Echo time

TR

Repetition time

Xeno

Xenogeneic

Notes

Acknowledgements

Supported by a grant from Siemens AG, National Heart, Lung, and Blood Institute (NIH R33-HL089029), and the Maryland Stem Cell Research Foundation (2008-MDSCRFII-0399).

Author contributions

GW was responsible for acquiring imaging data, image processing algorithm development, statistical analysis, result interpretation, and drafting the initial manuscript. YF was responsible for XMRCaps production, animal model preparation, imaging acquisition, histopathology, and drafting the final manuscript. SMS assisted with study design, MR imaging sequence tuning, and manuscript preparation. SSH assisted with study design, coil tuning, and manuscript preparation. DLK was responsible for study conception design, animal model preparation, image acquisition, interpretation, critical review, and drafting the final manuscript.

Compliance with ethical standards

Conflict of interest

DLK has received research grants from Siemens AG and BTG plc. SMS is a former employee of Siemens Healthcare.

Ethical standards

All animal studies were approved by the Institutional Animal Care and Use Committee.

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Copyright information

© European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2018

Authors and Affiliations

  • Guan Wang
    • 1
    • 2
  • Yingli Fu
    • 1
  • Steven M. Shea
    • 4
  • Shashank Sathyanarayana Hegde
    • 1
  • Dara L. Kraitchman
    • 1
    • 3
    Email author
  1. 1.Russell H. Morgan Department of Radiology and Radiological ScienceJohns Hopkins UniversityBaltimoreUSA
  2. 2.Electrical and Computer EngineeringJohns Hopkins UniversityBaltimoreUSA
  3. 3.Molecular and Comparative PathobiologyJohns Hopkins UniversityBaltimoreUSA
  4. 4.Department of Radiology, Stritch School of MedicineLoyola University ChicagoChicagoUSA

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