Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration
| Autor: | Eric Austin, Jon Smythe, Brian Kevin Park, Jack Sharkey, Harish Poptani, Patricia Murray, Joan Comenge, Michael Barrow, Dave J. Adams, Raphaël Lévy, Cai Astley, Bettina Wilm, Rachel Harwood, Ilaria Santeramo, Arthur Taylor, Claire Hutchinson, Lydia Beeken, Lauren Scarfe, Lorenzo Ressel, Matthew J. Rosseinsky |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cell type
Stromal cell Carcinogenesis Cell Preclinical models Mice SCID Mesenchymal Stem Cell Transplantation Regenerative medicine Cell Line Umbilical Cord lcsh:Biochemistry 03 medical and health sciences Route of administration Imaging Three-Dimensional 0302 clinical medicine In vivo Animals Humans Medicine Tissue Distribution lcsh:QD415-436 030304 developmental biology Mice Inbred BALB C Osteosarcoma 0303 health sciences lcsh:R5-920 Cell therapies Mesenchymal stem/stromal cells business.industry Research Mesenchymal stem cell Mesenchymal Stem Cells Magnetic Resonance Imaging 3. Good health medicine.anatomical_structure Cell tracking 030220 oncology & carcinogenesis Multi-modal imaging Injections Intravenous Cancer research Safety business lcsh:Medicine (General) Preclinical imaging |
| Zdroj: | Stem Cell Research & Therapy, Vol 9, Iss 1, Pp 1-17 (2018) STEM CELL RESEARCH & THERAPY Stem Cell Research and Therapy Stem Cell Research & Therapy |
| ISSN: | 1757-6512 |
| Popis: | BackgroundCell-based regenerative medicine therapies are now frequently tested in clinical trials. In many conditions, cell therapies are administered systemically, but there is little understanding of their fate, and adverse events are often under-reported. Currently, it is only possible to assess safety and fate of cell therapies in preclinical studies, specifically by monitoring animals longitudinally using multimodal imaging approaches. Here, using a suite of in vivo imaging modalities to explore the fate of a range of human and murine cells, we investigate how route of administration, cell type and host immune status affect the fate of administered cells.MethodsWe applied a unique imaging toolkit combining bioluminescence, optoacoustic and magnetic resonance imaging modalities to assess the safety of different human and murine cell types by following their biodistribution and persistence in mice following administration into the venous or arterial system. Results: Longitudinal imaging analyses (i) suggested that the intra-arterial route may be more hazardous than intravenous administration for certain cell types; (ii) revealed that the potential of a mouse mesenchymal stem/stromal cell (MSC) line to form tumours, depended on administration route and mouse strain; and (iii) indicated that clinically tested human umbilical cord (hUC)-derived MSCs can transiently and unexpectedly proliferate when administered intravenously to mice.ConclusionsIn order to perform an adequate safety assessment of potential cell-based therapies, a thorough understanding of cell biodistribution and fate post administration is required. The non-invasive imaging toolbox used here can expose not only the general organ distribution of these therapies, but also a detailed view of their presence within different organs and, importantly, tumourigenic potential. Our observation that the hUC-MSCs but not the human bone marrow (hBM)-derived MSCs persisted for a period in some animals, suggests that therapies with these cells should proceed with caution. |
| Databáze: | OpenAIRE |
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