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  Quantitative efficacy and fate of mesenchymal stromal cells targeted to cardiac sites by radiofrequency catheter ablation

Malik, R., Darche, F. F., Rivinius, R., Seckinger, A., Krause, U., Koenen, M., et al. (2020). Quantitative efficacy and fate of mesenchymal stromal cells targeted to cardiac sites by radiofrequency catheter ablation. Cell Transplantation, 29: 963689720914236, pp. 1-12. doi:10.1177/0963689720914236.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0006-3B47-9 Version Permalink: https://hdl.handle.net/21.11116/0000-0007-D3A8-D
Genre: Journal Article

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 Creators:
Malik, Rizwan, Author
Darche, Fabrice F., Author
Rivinius, Rasmus, Author
Seckinger, Anja, Author
Krause, Ulf, Author
Koenen, Michael1, Author           
Thomas, Dierk, Author
Katus, Hugo A., Author
Schweizer, Patrick A., Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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Free keywords: catheter ablation; cell therapy; homing; mesenchymal stromal cells
 Abstract: Engraftment and functional integration of stem cells or stem cell-derived cells within cardiac tissue is an important prerequisite for cell replacement therapy aiming at the treatment of heart disease. Recently, a novel intravenous approach for application of mesenchymal stromal cells (MSCs) to cardiac sites has been established using radiofrequency catheter ablation (RFCA)-guided targeting, bypassing the need for open chest surgery or direct myocardial cell injection. However, little is known about the quantitative efficacy and longevity of this strategy. We performed selective power-controlled RFCA with eight ablation pulses (30 W, 60 s each) to induce heat-mediated lesions at the right atrial appendices (RAAs) of pigs. Different concentrations of human bone marrow-derived MSCs (105 to 1.6 × 106 cells/kg bodyweight) labeled with superparamagnetic iron oxide (SPIO) particles were infused intravenously in nine pigs one d after RFCA treatment and hearts were explanted 8 d later to quantify the number of engrafted cells. Prussian blue staining revealed high numbers of SPIO-labeled cells in areas surrounding the RFCA-induced lesions. Cell numbers were evaluated by quantitative real-time polymerase chain reaction using specific primers for human MSCs (hMSCs), which indicated that up to 106 hMSCs, corresponding to ∼3.9% of the systemically applied human cells, engrafted within the RAAs of RFCA-treated pigs. Of note, infused hMSCs were observed in nontargeted organs, as well, but appeared at very low concentrations. To assess long-term deposition of MSCs, RAAs of three pigs were analyzed after 6 months, which revealed few persisting hMSCs at targeted sites. RFCA-mediated targeting of MSCs provides a novel minimal invasive strategy for cardiac stem cell engraftment. Qualitative and quantitative results of our large animal experiments indicate an efficient guidance of MSCs to selected cardiac regions, although only few cells remained at targeted sites 6 mo after cell transplantation.

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Language(s): eng - English
 Dates: 2020-02-072019-12-312020-02-282020-03-24
 Publication Status: Published online
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1177/0963689720914236
URI: https://www.ncbi.nlm.nih.gov/pubmed/32207339
 Degree: -

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Title: Cell Transplantation
  Other : Cell Transplant.
Source Genre: Journal
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Publ. Info: Elmsford, NY : No longer published by Elsevier
Pages: - Volume / Issue: 29 Sequence Number: 963689720914236 Start / End Page: 1 - 12 Identifier: ISSN: 0963-6897
CoNE: https://pure.mpg.de/cone/journals/resource/954925580138