transplantation 2.jpg

Kidney Transplantation

Kidney transplantation is a save and well established technique to compensate loss of renal function in humans. Immunosuppressive therapy has improved during the last decade but still acute and chronic rejection are important complications after transplantation.

Organ Transplantation

In-vivo Models

Depending on the strain combination for donor and recipients models for acute tubulo-interstitial rejection and for chronic rejection are established. In these models therapeutic approaches can be studied to prevent either inflammatory mechanisms in acute rejection or progressive fibrosis in chronic rejection.

Available Readouts

  1. Survival

  2. Kidney function

    • Serum-creatinine and BUN

    • Glomerular filtration rate (GFR)

    • Albuminuria

  3. Renal morphology

    • H & E, PAS Histology

  4. Oxidative stress

    • Reactive Oxygen Species (ROS)

  5. Inflammation

    • Cytokine/chemokine profile in serum and kidney tissue

    • Immunophenotyping of infiltrating leukocytes

  6. Apoptosis

    • TUNEL assay

  7. Immunohistochemistry and RT-PCR for specific markers of interest

Techniques

  • Clinical chemistry

  • Flow cytometry including Bead-based flow cytometry

  • Histology (H&E, Masson Trichrome, Periodic Acid Schiff (PAS) staining)

  • Renal function (Inulin and PAH clearance)

  • TUNEL assay

  • Molecular biology (Real-Time PCR, Western blot)

 

Need further Readouts? We routinely develop new models to fit our cutomer needs.

 

Speak with us for tailor-made solutions!

 

 

In vitro (ex vivo) Models

  1. T-cell priming

    • Mixed lymphocyte reaction (MLR) assay

  2. Adhesion molecules​ 

    • ​Primary cultures of mouse aortic endothelial cells

  3. Chemotaxis​​​

Kidney transplantation - relevant Publications

 

A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

Gueler F, Shushakova N, Mengel M, Hueper K, Chen R, Liu X, Park JK, Haller H, Wensvoort G, Rong S. PLoSOne. 2015 Jan 24; 10(1): e0115709. PMID: 25617900

Renal PKC-e deficiency attenuates acute kidney injury and ischemic allograft injury via TNF-a-dependent inhibition of apoptosis and inflammation.

Rong S, Hueper K, Kirsch T, Greite R, Klemann C, Mengel M, Meier M, Menne J, Leitges M, Susnik N, Meier M, Haller H, Shushakova N, Gueler F. Am J Physiol Renal Physiol. 2014 Sep 15; 307(6): F718 - 26. PMID: 25056349

Bβ(15-42) attenuates the effect of ischemia-reperfusion injury in renal transplantation.

Sörensen I, Rong S, Susnik N, Gueler F, Shushakova N, Albrecht M, Dittrich AM, von Vietinghoff S, Becker JU, Melk A, Bohlmann A, Reingruber S, Petzelbauer P, Haller H, Schmitt R. J Am Soc Nephrol. 2011 Oct; 22 (10): 1887 - 96. PMID: 21841063

Complement 5a receptor inhibition improves renal allograft survival.

Gueler F, Rong S, Gwinner W, Mengel M, Bröcker V, Schön S, Greten TF, Hawlisch H, Polakowski T, Schnatbaum K, Menne J, Haller H, Shushakova N. J Am Soc Nephrol. 2008 Dec; 19 (12): 2302 - 12. PMID: 18753257

CCL19-IgG prevents allograft rejection by impairment of immune cell trafficking.

Ziegler E, Gueler F, Rong S, Mengel M, Witzke O, Kribben A, Haller H, Kunzendorf U, Krautwald S. J Am Soc Nephrol. 2006 Sep; 17 (9): 2521 - 32. Epub 2006 Aug 9. PMID: 16899521

Heart Transplantation

Heart transplantation is a well established technique to study mechanisms and therapeutic approaches to prevent solid organ transplant rejection.

 

In vivo Models

Depending on the strain combination for donor and recipients models for acute and for chronic rejection are possible. Heterotopic vascularized heart transplantation is carried out according to the method of Corry et al. (Transplantation 1973). For acute rejection C57BL/6 (H-2b) and BALB/c (H-2d) are used as donors and recipients. Animals are anesthetized with isoflurane. The donor pulmonary artery will be anastomosed to the recipient´s inferior vena cava and the donor ascending aorta will be anastomosed to the abdominal aorta, respectively. Graft function will be assessed by daily palpation. Rejection is defined as the lack of palpable cardiac contraction. In this model of acute htx rejection mortality is 90% within 10 days.

Available Readouts

  1. Survival

  2. Morphology

    • H & E, PAS Histology

  3. Level of alloantibodies

    • Flow cytometry

  4. Immunohistochemistry and RT-PCR for specific markers of interest

Techniques

  • Flow cytometry including Bead-based flow cytometry

  • Histology (H&E, Masson Trichrome, Periodic Acid Schiff (PAS) staining)

  • Molecular biology (Real-Time PCR, Western blot)

 

 

Need further Readouts? We routinely develop new models to fit our cutomer needs.

 

Speak with us for tailor-made solutions!

Heart transplantation - relevant Publications

T2 Mapping for Noninvasive Assessment of Interstitial Edema in Acute Cardiac Allograft Rejection in a Mouse Model of Heterotopic Heart Transplantation.

Hartung D, Hueper K, Chen R, Gutberlet M, Wacker F, Meier M, Rong S, Jang MS, Bräsen JH, Gueler F. Invest Radiol. 2018 May; 53(5): 271 - 277. PMID: 29261532.

A novel and knotless technique for heterotopic cardiac transplantation in mice.

Mao M, Liu X, Tian J, Yan S, Lu X, Gueler F, Haller H, Rong S. J Heart Lung Transplant. 2009 Oct; 28(10): 1102 - 6. PMID: 19782294.

Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse.

Reichardt P, Dornbach B, Rong S, Beissert S, Gueler F, Loser K, Gunzer M. Blood. 2007 Sep 1; 110(5): 1519 - 29. PMID: 17392507.

CCL19-IgG prevents allograft rejection by impairment of immune cell trafficking.

Ziegler E, Gueler F, Rong S, Mengel M, Witzke O, Kribben A, Haller H, Kunzendorf U, Krautwald S. J Am Soc Nephrol. 2006 Sep; 17 (9): 2521 - 32. Epub 2006 Aug 9. PMID: 16899521

STAT-1 and AP-1 decoy oligonucleotide therapy delays acute rejection and prolongs cardiac allograft survival.

Hölschermann H, Stadlbauer TH, Wagner AH, Fingerhuth H, Muth H, Rong S, Güler F, Tillmanns H, Hecker M. Cardiovasc Res. 2006 Aug 1; 71(3): 527 - 36. PMID: 16822491.

Phenos - your independent contract research organisation

Contact us today. We routinely develop new models to fit your needs.

Image by National Cancer Institute