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Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres

Gene Therapy volume 13, pages 1320–1327 (2006)Cite this article

Abstract

Gelatin hydrogel microspheres (GHMs) have been reported as novel non-viral vectors for gene or protein delivery (GHM therapy). However, the components of an effective catheter-based delivery strategy for GHM therapy are unknown. We evaluated the effectiveness of three catheter-based strategies for cardiac GHM therapy: (1) antegrade injection (AI) via coronary arteries; (2) retrograde injection (RI) via coronary veins; and (3) direct myocardial injection (DI) via the coronary sinus. AI distributed microspheres homogeneously throughout the target area with 73±11% retention. RI scattered microspheres non-homogenously with 22±8% retention. DI distributed microspheres in the needle-advanced area with 47±14% retention. However, despite high efficiency, AI did not show biological effects of inducing angiogenesis from basic fibroblast growth factor bound to GHMs. Furthermore, focal micro-infarctions, owing to micro-embolism of aggregated GHMs into small coronary arterioles, were detected in the AI group. Conversely, only RI and DI groups displayed increased coronary flow reserve. DI groups also demonstrated increased capillary density. These results suggest that RI and DI are effective for cardiac GHM therapy, while AI appears inappropriate owing to the risk of focal infarctions.

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Acknowledgements

We thank Research Institute for Production Development (Kyoto, Japan), Kirin Brewery Co. Ltd (Tokyo, Japan), Medtronic Vascular (CA, USA), and MID Co. Ltd (Fukuoka, Japan) for their financial support. This study was funded in part by a grant (R01-HL-78691) to Roger J Hajjar, MD from the National Heart Lung and Blood Institute.

We thank Jennifer McGregor, Catherine McMahon, and James Lough (Massachusetts General Hospital) for their technical help with animal care and handling.

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Authors and Affiliations

  1. Cardiology Laboratory for Integrative Physiology and Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    K Hoshino, R Yoneyama, Y Kawase, H Q Ly, R J Hajjar & M Hayase

  2. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    K Hoshino, T Kimura, Y Furukawa, K Ono & T Kita

  3. Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    A M De Grand & J V Frangioni

  4. Department of Radiology and Molecular Imaging Center, Beth Israel Deaconess Medical Center, Boston, MA, USA

    A M De Grand & J V Frangioni

  5. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    S Houser

  6. Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan

    T Kushibiki & Y Tabata

  7. Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    R J Hajjar

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  1. K Hoshino
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  2. T Kimura
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Correspondence to K Hoshino.

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Hoshino, K., Kimura, T., De Grand, A. et al. Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres. Gene Ther 13, 1320–1327 (2006). https://doi.org/10.1038/sj.gt.3302793

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  • DOI: https://doi.org/10.1038/sj.gt.3302793

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