Dosing Limitation for Intra-Renal Arterial Infusion of Mesenchymal Stromal Cells
| Autor: | Anders Munk, Christina Søndergaard Duvald, Michael Pedersen, Stine Lohmann, Anna Krarup Keller, Bjarne Kuno Møller, Steffen Ringgaard, Niels Henrik Buus, Bente Jespersen, Marco Eijken |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Inflammation
Mesenchymal Stem Cells/metabolism Swine Organic Chemistry Mesenchymal Stem Cells General Medicine Kidney Mesenchymal Stem Cell Transplantation mesenchymal stem/stromal cells intra-arterial renal infusion coagulation safety kidney disease adverse effects Catalysis Computer Science Applications Inorganic Chemistry Kidney/pathology Mesenchymal Stem Cell Transplantation/methods Animals Physical and Theoretical Chemistry Molecular Biology Spectroscopy Glomerular Filtration Rate Inflammation/pathology |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 15; Pages: 8268 Munk, A, Duvald, C S, Pedersen, M, Lohmann, S, Keller, A K, Møller, B K, Ringgaard, S, Buus, N H, Jespersen, B & Eijken, M 2022, ' Dosing Limitation for Intra-Renal Arterial Infusion of Mesenchymal Stromal Cells ', International Journal of Molecular Sciences, vol. 23, no. 15, 8268 . https://doi.org/10.3390/ijms23158268 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23158268 |
| Popis: | The immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) make MSC therapy a promising therapeutic strategy in kidney disease. A targeted MSC administration via the renal artery offers an efficient delivery method with limited spillover to other organs. Although local administration alleviates safety issues with MSCs in systemic circulation, it introduces new safety concerns in the kidneys. In a porcine model, we employed intra-renal arterial infusion of ten million allogenic adipose tissue-derived MSCs. In order to trigger any potential adverse events, a higher dose (hundred million MSCs) was also included. The kidney function was studied by magnetic resonance imaging after the MSC infusion and again at two weeks post-treatment. The kidneys were assessed by single kidney glomerular filtration rate (skGFR) measurements, histology and inflammation, and fibrosis-related gene expression. None of the measured parameters were affected immediately after the administration of ten million MSCs, but the administration of one hundred million MSCs induced severe adverse events. Renal perfusion was reduced immediately after MSC administration which coincided with the presence of microthrombi in the glomeruli and signs of an instant blood-mediated inflammatory reaction. At two weeks post-treatment, the kidneys that were treated with one hundred million MSCs showed reduced skGFR, signs of tissue inflammation, and glomerular and tubular damage. In conclusions, the intra-renal administration of ten million MSCs is well-tolerated by the porcine kidney. However, higher concentrations (one hundred million MSCs) caused severe kidney damage, implying that very high doses of intra-renally administered MSCs should be undertaken with caution. |
| Databáze: | OpenAIRE |
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