Your browser doesn't support javascript.
loading
Mesenchymal Stromal Cells Are Retained in the Porcine Renal Cortex Independently of Their Metabolic State After Renal Intra-Arterial Infusion.
Sierra-Parraga, Jesus M; Munk, Anders; Andersen, Christine; Lohmann, Stine; Moers, Cyril; Baan, Carla C; Ploeg, Rutger J; Pool, Merel; Keller, Anna K; Møller, Bjarne K; Leuvenink, Henri; Hoogduijn, Martin J; Jespersen, Bente; Eijken, Marco.
Afiliação
  • Sierra-Parraga JM; Nephrology and Transplantation, Internal Medicine Department, University Medical Center Rotterdam, Erasmus MC, Rotterdam, the Netherlands.
  • Munk A; Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Andersen C; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Lohmann S; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Moers C; Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Baan CC; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Ploeg RJ; Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Pool M; Nephrology and Transplantation, Internal Medicine Department, University Medical Center Rotterdam, Erasmus MC, Rotterdam, the Netherlands.
  • Keller AK; Nuffield Department of Surgical Sciences and Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
  • Møller BK; Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Leuvenink H; Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Hoogduijn MJ; Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
  • Jespersen B; Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Eijken M; Nephrology and Transplantation, Internal Medicine Department, University Medical Center Rotterdam, Erasmus MC, Rotterdam, the Netherlands.
Stem Cells Dev ; 28(18): 1224-1235, 2019 09 15.
Article em En | MEDLINE | ID: mdl-31280676
The regenerative capacities of mesenchymal stromal cells (MSCs) make them suitable for renal regenerative therapy. The most common delivery route of MSC is through intravenous infusion, which is associated with off-target distribution. Renal intra-arterial delivery offers a targeted therapy, but limited knowledge is available regarding the fate of MSCs delivered through this route. Therefore, we studied the efficiency and tissue distribution of MSCs after renal intra-arterial delivery to a porcine renal ischemia-reperfusion model. MSCs were isolated from adipose tissue of healthy male pigs, fluorescently labeled and infused into the renal artery of female pigs. Flow cytometry allowed MSC detection and quantification in tissue and blood. In addition, quantitative polymerase chain reaction was used to trace MSCs by their Y-chromosome. During infusion, a minor number of MSCs left the kidney through the renal vein, and no MSCs were identified in arterial blood. Ischemic and healthy renal tissues were analyzed 30 min and 8 h after infusion, and 1-4 × 104 MSCs per gram of tissue were detected, predominantly, in the renal cortex, with a viability >70%. Confocal microscopy demonstrated mainly glomerular localization of MSCs, but they were also observed in the capillary network around tubuli. The infusion of heat-inactivated (HI) MSCs, which are metabolically inactive, through the renal artery showed that HI-MSCs were distributed in the kidney in a similar manner to regular MSCs, suggesting a passive retention mechanism. Long-term MSC survival was analyzed by Y-chromosome tracing, and demonstrated that a low percentage of the infused MSCs were present in the kidney 14 days after administration, while HI-MSCs were completely undetectable. In conclusion, renal intra-arterial MSC infusion limited off-target engraftment, leading to efficient MSC delivery to the kidney, most of them being cleared within 14 days. MSC retention was independent of the metabolic state of MSC, indicating a passive mechanism.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Transplante de Células-Tronco Mesenquimais / Células-Tronco Mesenquimais / Córtex Renal Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Transplante de Células-Tronco Mesenquimais / Células-Tronco Mesenquimais / Córtex Renal Idioma: En Ano de publicação: 2019 Tipo de documento: Article