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Dosing Limitation for Intra-Renal Arterial Infusion of Mesenchymal Stromal Cells.
Munk, Anders; Duvald, Christina Søndergaard; Pedersen, Michael; Lohmann, Stine; Keller, Anna Krarup; Møller, Bjarne Kuno; Ringgaard, Steffen; Buus, Niels Henrik; Jespersen, Bente; Eijken, Marco.
Afiliación
  • Munk A; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Duvald CS; Department of Urology, Aarhus University Hospital, 8200 Aarhus N, Denmark.
  • Pedersen M; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Lohmann S; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Keller AK; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Møller BK; Department of Urology, Aarhus University Hospital, 8200 Aarhus N, Denmark.
  • Ringgaard S; Department of Urology, Aarhus University Hospital, 8200 Aarhus N, Denmark.
  • Buus NH; Department of Clinical Immunology, Aarhus University Hospital, 8200 Aarhus N, Denmark.
  • Jespersen B; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Eijken M; Department of Renal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark.
Int J Mol Sci ; 23(15)2022 Jul 27.
Article en En | MEDLINE | ID: mdl-35955404
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Mesenquimatosas / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Mesenquimatosas / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Suiza