Pre-clinical renal transplantation Bente Jespersen, professor Renal - - PowerPoint PPT Presentation

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Pre-clinical renal transplantation Bente Jespersen, professor Renal - - PowerPoint PPT Presentation

Dec 22, 2023 632 likes •898 views

Pre-clinical renal transplantation Bente Jespersen, professor Renal Medicine Aarhus University Hospital Denmark Porcine kidney similar to human anatomy physiology Ethics Animal wellfare Henri Leuvenink Ulla Mldrup Danish/yorkshire

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Pre-clinical renal transplantation

Bente Jespersen, professor Renal Medicine Aarhus University Hospital Denmark

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Porcine kidney similar to human – anatomy physiology Ethics Animal wellfare

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Henri Leuvenink Ulla Møldrup

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Danish/yorkshire landrace Göttingen minipigs Growing! 15 kg – 65 kg Adult - 35 kg

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Renal transplantation in the pig

Brain death models Circulatory death model Acute models Survival models

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Allogeneic blood for NMP

Blood typing at the delivery farm

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Need of immunosuppression?

  • Not with 10 h observation after tx
  • Not in autotransplantations
  • In allotx survival experiments tissue typing

and immunosuppression is possible

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Brain death models in the pig

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 Brain dead donor  High risk of delayed graft function:

Long cold ischemia time (22h) 65 kg donor to 15 kg recipients

 RIC with clamping aorta  10 hour follow up after kidney reperfusion

Ischemia 5 min Ischemia 5 min Ischemia 5 min Ischemia 5 min Reperfusion 5 min Reperfusion 5 min Reperfusion 5 min Reperfusion 5 min

2012; 25: 1002-12

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  • Improved plasma perfusion

in both cortex and medulla in RIC compared to sham

  • The difference was time

dependent and increased

  • ver time (p=0.001 and 0.024

respectively)

Transpl Int. 2012; 25: 1002-12

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  • Testing drugs
  • Testing fluid therapy regimens
  • Testing drugs
  • Testing device
M U N K S G A A R D BENTE J EPERSEN OG J ENS AAGE KØLSEN PE TERSEN

P raktisk væske- og elektrolytbehandling

  • 3. UDGAVE

Fig. 1

Porcine DBD renal transplantation model Porcine IRI and vascular occlusion models

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Organ perfusion and metabolism after experimental brain death

MRI: Hyperpolarized pyruvate Isolated perfused kidney model: Tritiated glucose

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MSC in kidney repair

  • Better GFR in human renovascular

hypertension Saad et al. J Am Soc Nephrol 2017; 28: 2777-85

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1) MSC MRI safety study 2) Fluorescent (Qtracker) MSC tracking 3) MSC survival - Y chromosome tracking 4) Effects of MSC given before transplantation

MSC in the renal artery

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Anders Munk

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Kidney transplant regeneration with MEsenchymal stem cells in normothermic ex-situ PErfusion in Pigs

Rotterdam, Groningen, Oxford and Aarhus

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Female pigs autotransplanted 75 min WIT + 16 h CSS or oxygenated HMP +/- NMP 10 m male MSC 14 days survival model

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SCS or oxHMP +/- NMP +/- MSC

Donation after circulatory death autotransplantation model

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Autotransplantation with 14 days survival

Kidney transplant regeneration with MEsenchymal stem cells in normothermic ex-situ PErfusion in Pigs Marco Eijken Anna Keller Stine Lohmann

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Autotransplantation with 14 days survival

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Autotransplantation model – at 14 days

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Else Tønnesen Anders Munk Michael Pedersen Christoffer Laustsen Chris Amdisen Peter Søndergaard Kristian Ravlo Niels Secher Jonathan Kunish Niels Moeslund Lise Nielsen Gert van Rijt Anne van Erp Letizia Lo Faro Honglei Huang