Gold Mesoporous Silica-Coated Nanoparticles for Quantifying and Qualifying Mesenchymal Stem Cell Distribution; a Proof-of-Concept Study in Large Animals

ACS Applied Bio Materials, vol. 8, pp. 1511–1523

Abstract

Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential across a wide range of diseases including (multi) organ injury in neonates. Despite the reported preclinical successes of MSC therapy, a major challenge in their clinical translation is a limited understanding of their biodistribution after administration. This knowledge gap needs to be addressed to allow clinical implementation. Accordingly, in this study, we propose that silica-coated gold nanoparticles (AuMS) are a promising tool for in vivo MSC tracing. This study explores the use of AuMS for both qualitative and quantitative MSC tracking in vivo after intravenous (I.V.) administration in a translational ovine model of preterm birth. Additionally, we assess the impact of AuMS labeling on the immunomodulatory functions of MSC, which play an important role in the therapeutic potency of these cells. Quantitative and qualitative assessment of AuMS-labeled MSC was performed in vivo using fluorescent microscopy and inductively coupled plasma mass spectrometry (ICP-MS), respectively. AuMS localization in the liver, spleen, and lung was demonstrated. In vitro studies showed that AuMS cellular uptake occurs within 6 h and remains internalized up to 72 h. Labeled MSC maintained their immune phenotype and did not alter their immunomodulatory capacity and proliferation abilities. Overall, we demonstrate that AuMS is a promising, biocompatible nanoprobe for MSC tracing up to 72 h post-I.V. administration.

Authors 12

1. Lotte C. C. Smeets

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Pediatrics

   GROW Research Institute for Oncology and Reproduction

   MERLN Institute for Technology-Inspired Regenerative Medicine

   Maastricht University

   Maastricht University Medical Center+, MosaKids Children’s Hospital

   Department of Pediatrics, Maastricht University Medical Center+, MosaKids Children's Hospital, Maastricht 6200 MD, The Netherlands

   GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht 6200 MD, The Netherlands

   MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands

2. Ezgi Sengun

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Laboratory Medicine, Laboratory of Medical Immunology

   Radboud University Medical Center Nijmegen

   Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Nijmegen 6500 HB, The Netherlands

3. Chloe Trayford

   Maastricht University

   Affiliation as printed

   MERLN Institute for Technology-Inspired Regenerative Medicine

   Maastricht University

   MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands

4. Bram van Cranenbroek

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Laboratory Medicine, Laboratory of Medical Immunology

   Radboud University Medical Center Nijmegen

   Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Nijmegen 6500 HB, The Netherlands

5. Marien Isaäk de Jonge

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Laboratory Medicine, Laboratory of Medical Immunology

   Radboud University Medical Center Nijmegen

   Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Nijmegen 6500 HB, The Netherlands

6. Katiuscia Dallaglio

   Chiesi (Italy)

   Affiliation as printed

   Chiesi Farmaceutici S.p.A

   Global Rare Diseases R&D

   Global Rare Diseases R&D, Chiesi Farmaceutici S.p.A., Parma 43122, Italy

7. Matthias Christian Hütten

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Pediatrics

   GROW Research Institute for Oncology and Reproduction

   Maastricht University

   Maastricht University Medical Center+, MosaKids Children’s Hospital

   Department of Pediatrics, Maastricht University Medical Center+, MosaKids Children's Hospital, Maastricht 6200 MD, The Netherlands

   GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht 6200 MD, The Netherlands

8. Mark Schoberer Aachen Division of Neonatology Department of Pediatrics

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Division of Neonatology, Department of Pediatrics

   University Hospital RWTH Aachen

   Division of Neonatology, Department of Pediatrics, University Hospital RWTH Aachen, Aachen 52074, Germany

9. Daan R. M. G. Ophelders

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Pediatrics

   GROW Research Institute for Oncology and Reproduction

   Maastricht University

   Maastricht University Medical Center+, MosaKids Children’s Hospital

   Department of Pediatrics, Maastricht University Medical Center+, MosaKids Children's Hospital, Maastricht 6200 MD, The Netherlands

   GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht 6200 MD, The Netherlands

10. Tim G. A. M. Wolfs

    Maastricht University Medical Centre · Maastricht University

    Affiliation as printed

    Department of Pediatrics

    GROW Research Institute for Oncology and Reproduction

    Maastricht University

    Maastricht University Medical Center+, MosaKids Children’s Hospital

    Department of Pediatrics, Maastricht University Medical Center+, MosaKids Children's Hospital, Maastricht 6200 MD, The Netherlands

    GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht 6200 MD, The Netherlands

11. Renate G.V.D. Molen

    Radboud University Nijmegen · Radboud University Medical Center

    Affiliation as printed

    Department of Laboratory Medicine, Laboratory of Medical Immunology

    Radboud University Medical Center Nijmegen

    Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Nijmegen 6500 HB, The Netherlands

12. Sabine van Rijt corresponding

    Maastricht University

    Affiliation as printed

    MERLN Institute for Technology-Inspired Regenerative Medicine

    Maastricht University

    MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands