Azene, Nicole

Cook, Judy A

Ehtiati, Tina

Flammang, Aaron

Fu, Yingli

Gilson, Wesley

Guehring, Jens

Johnston, Peter V

Kraitchman, Dara

Weiss, Clifford R

English

PubMed

Fu Yingli

Azene Nicole

Ehtiati Tina

Flammang Aaron

Guehring Jens

Gilson Wesley

Cook Judy A

Weiss Clifford R

Johnston Peter V

Kraitchman Dara

Directory of Open Access Journals

Journal of Cardiovascular Magnetic Resonance

XFM-guided delivery of imaging-visible human mesenchymal stem cells into the pericardial space in a porcine model

Yingli Fu

Nicole Azene

Tina Ehtiati

Aaron Flammang

Jens Guehring

Wesley Gilson

Judy A Cook

Clifford R Weiss

Peter V Johnston

Dara Kraitchman

Crossref

Springer - Publisher Connector

POSTER PRESENTATION Open Access
XFM-guided delivery of imaging-visible human
mesenchymal stem cells into the pericardial
space in a porcine model
Yingli Fu1*, Nicole Azene2, Tina Ehtiati3, Aaron Flammang3, Jens Guehring4, Wesley Gilson3, Judy A Cook1,
Clifford R Weiss1, Peter V Johnston5, Dara Kraitchman1,2
From 15th Annual SCMR Scientific Sessions
Orlando, FL, USA. 2-5 February 2012
Background
Transmyocardial delivery of stem cells in the setting of
acute myocardial ischemia has shown promise to pre-
vent adverse ventricular remodeling1. However, the effi-
cacy is limited by poor cell retention and low survival
rates, even for autologous cells. Intrapericardial delivery
of microencapsulated stem cells may offer a local and
minimally invasive route to enhance cell survival and
retention. In this study, we assess the delivery of human
mesenchymal stem cells (hMSCs) in a radiopaque
microcapsule to the pericardium using x-ray fused with
magnetic resonance imaging (XFM) in a porcine model.
Methods
Stem cell microencapsulation was performed using a
modification of the alginate microencapsulation method
by the addition of 10% (w/v) BaSO4 (BaCaps, Fig.1A)2.
Female Yorkshire pigs (~25 kg, n=7) were randomized
to receive either empty BaCaps (~10 ml), naked hMSCs
(1x108), saline, or BaCaps with hMSCs (8x107) using a
percutaneous approach. Prior to delivery, cine breath-
held short-axis images were acquired to determine ven-
tricular function (Argus, Siemens). A navigator-gated 3D
whole heart MRI (1.5T Espree, Siemens SSFP, TR/
TE=290/1.67 ms, FOV=320x240 mm, image
matrix=256x173, iPAT=2, slice=64, slice thickness=2
mm) was also obtained to define ventricular borders for
intrapericardial injection. A cardiac-gated c-arm CT
(dynaCT, Axiom Artis dFA, Siemens, 190° rotation; 0.5°
angle; 20s acquisition; 48 cm FOV) was then obtained
and fused with the whole heart MRI and overlaid on
live fluoroscopy to guide percutaneous access to the
pericardial space. For chronic studies, MRI and c-arm
CT imaging were repeated one week after injection.
Animals were sacrificed immediately or one week post-
delivery for histological analysis.
Results
The viability of Ba-encapsulated hMSCs was 94.8±6%
two days after encapsulation (Fig.1B). Using XFM
(Fig.1C), successful puncture and delivery of BaCaps or
Ba-encapsulated hMSCs was achieved in all animals.
BaCaps were detected on fluoroscopic and c-arm CT
images immediately and one week after delivery
(Fig.1D). Whereas BaCaps were free floating immedi-
ately after delivery, at one week the BaCaps had consoli-
dated as a pseudo epicardial tissue patch. Cardiac
function was maintained 1 week post-delivery (LVEF:
36.8±4% at baseline vs. 41.5±5% at 1 week, n=5). Peri-
cardial adhesions and effusion were absent at one week.
Conclusions
XFM-guided intrapericardial injection of Ba-encapsu-
lated hMSCs was safe and reliable. This approach holds
promise for safe delivery of allogeneic cellular therapeu-
tics to the heart in patients without pericardial effusion.
Funding
Funding was provided by grants: R21/R33-HL89029,
MD-SCRFII-0399 and Siemens healthcare.
Author details
1Radiology, Johns Hopkins University, Baltimore, MD, USA. 2Molecular &
Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, USA.
3Siemens Corporate Research, Baltimore, MD, USA. 4Siemens Healthcare,
1Radiology, Johns Hopkins University, Baltimore, MD, USA
Full list of author information is available at the end of the article
Fu et al. Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):P63
http://www.jcmr-online.com/content/14/S1/P63
© 2012 Fu et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Erlangen, Germany, USA. 5Medicine, Johns Hopkins University, Baltimore, MD,
USA.
Published: 1 February 2012
doi:10.1186/1532-429X-14-S1-P63
Cite this article as: Fu et al.: XFM-guided delivery of imaging-visible
human mesenchymal stem cells into the pericardial space in a porcine
model. Journal of Cardiovascular Magnetic Resonance 2012 14(Suppl 1):P63.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Figure 1 A) Microscopic view of BaCaps. B) Fluorescence image of Ba-encapsulated hMSCs demonstrating high cell viability (green) 2 days after
encapsulation. C) XFM of the pig heart showing coronary vasculature (gray) and ventricular boundaries from MRI (colors). D) Cardiac-gated c-arm
CT image showing the persistence of BaCaps in pericardial space one week post delivery (arrows).
Fu et al. Journal of Cardiovascular Magnetic Resonance 2012, 14(Suppl 1):P63
http://www.jcmr-online.com/content/14/S1/P63
Page 2 of 2


http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3305735

XFM-guided delivery of imaging-visible human mesenchymal stem cells into the pericardial space in a porcine model

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals

Crossref

Springer - Publisher Connector

Springer - Publisher Connector