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Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation.
Thompson, Emily R; Bates, Lucy; Ibrahim, Ibrahim K; Sewpaul, Avinash; Stenberg, Ben; McNeill, Andrew; Figueiredo, Rodrigo; Girdlestone, Tom; Wilkins, Georgina C; Wang, Lu; Tingle, Samuel J; Scott, William E; de Paula Lemos, Henrique; Mellor, Andrew L; Roobrouck, Valerie D; Ting, Anthony E; Hosgood, Sarah A; Nicholson, Michael L; Fisher, Andrew J; Ali, Simi; Sheerin, Neil S; Wilson, Colin H.
Afiliação
  • Thompson ER; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • Bates L; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Ibrahim IK; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • Sewpaul A; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Stenberg B; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • McNeill A; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • Figueiredo R; Department of Radiology, Freeman Hospital, Newcastle upon Tyne, UK.
  • Girdlestone T; Department of Radiology, Freeman Hospital, Newcastle upon Tyne, UK.
  • Wilkins GC; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • Wang L; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • Tingle SJ; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Scott WE; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • de Paula Lemos H; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Mellor AL; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • Roobrouck VD; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Ting AE; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • Hosgood SA; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
  • Nicholson ML; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Fisher AJ; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Ali S; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Sheerin NS; ReGenesys, Leuven, Belgium.
  • Wilson CH; Athersys Inc., Cleveland, OH, USA.
Am J Transplant ; 21(4): 1402-1414, 2021 04.
Article em En | MEDLINE | ID: mdl-32506663
ABSTRACT
Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P = .009), decreased expression of injury biomarker NGAL (P = .012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P = .019, medulla P = .001), downregulation of interleukin (IL)-1ß (P = .050), and upregulation of IL-10 (P < .047) and Indolamine-2, 3-dioxygenase (P = .050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P < .001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Transplante de Rim Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Transplante de Rim Idioma: En Ano de publicação: 2021 Tipo de documento: Article