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
Open Access
Poster presentation
  • 564 Downloads

Keywords

Pericardial Effusion Human Mesenchymal Stem Cell Pericardial Space Pericardial Adhesion Cell Microencapsulation 

Background

Transmyocardial delivery of stem cells in the setting of acute myocardial ischemia has shown promise to prevent adverse ventricular remodeling1. However, the efficacy 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 ventricular 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.
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).

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 immediately after delivery, at one week the BaCaps had consolidated 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). Pericardial adhesions and effusion were absent at one week.

Conclusions

XFM-guided intrapericardial injection of Ba-encapsulated hMSCs was safe and reliable. This approach holds promise for safe delivery of allogeneic cellular therapeutics to the heart in patients without pericardial effusion.

Funding

Funding was provided by grants: R21/R33-HL89029, MD-SCRFII-0399 and Siemens healthcare.

Copyright information

© Fu et al; licensee BioMed Central Ltd. 2012

This article is published under license to 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.

Authors and Affiliations

  • Yingli Fu
    • 1
  • Nicole Azene
    • 2
  • Tina Ehtiati
    • 3
  • Aaron Flammang
    • 3
  • Jens Guehring
    • 4
  • Wesley Gilson
    • 3
  • Judy A Cook
    • 1
  • Clifford R Weiss
    • 1
  • Peter V Johnston
    • 5
  • Dara Kraitchman
    • 1
    • 2
  1. 1.RadiologyJohns Hopkins UniversityBaltimoreUSA
  2. 2.Molecular & Comparative PathobiologyJohns Hopkins UniversityBaltimoreUSA
  3. 3.Siemens Corporate ResearchBaltimoreUSA
  4. 4.Siemens HealthcareErlangenGermany, USA
  5. 5.MedicineJohns Hopkins UniversityBaltimoreUSA

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