Cardiothoracic Transplantation Laboratory–

Transplant Immunology and Stem Cell Immunobiology Group - Sonja Schrepfer, MD, PhD

In the Spotlight: Ransohoff Selected as Intel STS Finalist

Sonja Schrepfer, MD, PhD, and Julia Ransohoff
Sonja Schrepfer, MD, PhD
and Julia Ransohoff

Formerly sponsored by Westinghouse, and now sponsored by the Intel Corporation and the Intel Foundation, the Society for Science & the Public’s Science Talent Search (STS) is America’s oldest and most prestigious science research competition for high school seniors.

Julia Ransohoff, a high-school senior at Menlo-Atherton High School as well as a student investigator in the Cardiothoracic Transplantation Lab in the Department of Cardiothoracic Surgery, is one of this year’s finalists. Her instructor, Sonja Schrepfer, MD, PhD, will be accompanying Ransohoff to attend the week-long Science Talent Institute in Washington, DC.

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A Brief Overview of Our Research

(left to right) Julia, Katie, and Dr. Schrepfer working in the CT Lab

The overarching goal of our group is the development of a comprehensive research focus encompassing specific projects related to cardiac and lung transplantation as well as stem cell transplantation.

These projects range from molecular level (gene therapy) and cell biology investigations in murine models through to clinical projects. Bi-directional translational research is a crucial component in this regard, bridging the basic laboratory with the clinic. Thus, a strong translational program has the potential to generate key basic findings and apply these directly to clinical issues, leading to changes in clinical practice; likewise, important clinical issues can be taken to the basic laboratory for investigation. This provides a "bedside to bench to bedside" cycle of research activities that has the potential to change the practice of heart/lung and stem cell transplantation.

A number of the laboratory-based research efforts of our group are related to investigating immune responses to organ and cell transplantation. We are using in vivo models of heart and lung transplantation in mice and rats (heterotopic heart transplants, orthotopic aorta transplantations, orthotopic and heterotopic trachea transplantations, lung transplant models) as well as stem cell transplantation after myocardial infarction (LAD ligation). A variety of immunological in vitro assays are used to investigate cellular and molecular mechanism(s) of graft rejection (Elispots, donor-specific antibodies, Immunoknow Assay,...). Each cell line (lymphocytes, endothelial cells, smooth muscle cells, cardiomyocytes, stem cells, airway cells, ....) is being investigated in vitro for immuno-response and characterization.


Dr. Toby Deuse
Molecular biology lab

Dr. Christoph Peter
Collaboration Cooke lab, CV medicine

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Ongoing Basic Research Projects

Solid Organ Transplantation


Heterotopic heart transplantation

Membrane Cytokine Arrays
 To assess intragraft cytokine release

Histology 5 days after heterotopic heart transplantation.
The upper photomicrographs depict representative mid-graft cross sections 5 days after heterotopic heart transplantation for the groups investigated (R348= JAK3 inhibitor; rapamycin= mTOR inhibitor). Histologic sections stained with H&E (original magnification ×200) were used to assess acute rejection. Immunostaining on ED1 and CD3 (original magnification ×400) was performed to assess cell densities of macrophages and lymphocytes, respectively.

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Stem Cell Transplantation as Regenerative Therapy


CSFE labeled adult stem cells

CSFE and DAPI labeled adult stem cells


Stable ex-vivo transduction of adult stem cells to express firefly luciferase


Stem cells are isolated and transfered into a cell culture dish
to expand the cells and purify them.

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Group Members

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Awards

2008 - Foundation for Women’s Wellness Rachel Tawil Award, awarded to support research on cardiovascular disease in women, for Schrepfer's work on “The Gender Divide” project

2007 - Rudolf Pichlmayr Prize 2007 (from the German Transplant Society [DTG], named after the pioneer of German Transplant Medicine, the prize is awarded for outstanding achievement in the transplant field)

2007 - ISHLT Basic Science Award (International Society for Heart and Lung Transplantation)

2007 - Novartis Global Travel Award (Basic Science Symposium of the Transplantation Society 2007)

2007 - ATC Young Investigator Award (American Transplant Congress 2007).

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Group Publications

  1. van der Bogt KE, Sheikh AY, Schrepfer S, Hoyt G, Cao F, Ransohoff KJ, Swijnenburg RJ, Pearl J, Lee A, Fischbein M, Contag CH, Robbins RC, Wu JC. Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation. 2008 Sep 30;118(14 Suppl):S121-9.
  2. Schrepfer S, Swijnenburg RJ, Govaert J, Cao F, Ransohoff K, Sheikh A, Haddad M, Connolly A, Davis M, Robbins RC, Wu J. Immunosupressive therapy mitigates immunological rejection of human embryonic stem cell xenographs. Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12991-6.
  3. Swijnenburg RJ, Schrepfer S, Cao F, Pearl JI, Xie X, Connolly AJ, Robbins RC, Wu J. In Vivo Imaging of Embryonic Stem Cells Reveals Patterns of Survival and Rejection Following Transplantation. Stem Cells Dev 2008 May 20 (Epub ahead of print).
  4. Deuse T, Velotta JB, Hoyt G, Govaert JA, Taylor V, Masuda E, Herlaar E, Park G, Carroll D, Pelletier MP, Robbins RC, Schrepfer S.  Novel Immunosuppression: R348, a JAK3- and Syk-inhibitor, attenuates acute cardiac allograft rejection. Transplantation. 2008 Mar 27;85(6):885-92.
  5. Deuse T, Hoyt G, Koyanagi T, Robbins RC, Schrepfer S.  Prevention and Inhibition but not Reversion of Chronic Allograft Vasculopathy by FK778. Transplantation. 2008 Mar 27;85(6):870-7.
  6. Deuse T, Erben RG, Ikeno F, Behnisch B, Boeger R, Connolly AJ, Bergow C, Pelletier MP, Robbins RC, Schrepfer S. Introducing the first polymer-free leflunomide eluting stent. Atherosclerosis Feb 22 (Epub ahead of print).
  7. Rempf C, Ritter A, Schrepfer S, Freitag M, Standl T, Gottschalk A. Failed induction of heme oxygenase 1 in endothelial cells exposed to the hemoglobin based oxygen carrier oxyglobin(r). Artif Cells Blood Substit Immobil Biotechnol. 2008;36(1):34-44.
  8. Huellner MW, Schrepfer S, Weyand M, Weiner H, Wimplinger I, Eschenhagen T, Rau T. Inhibition of aldehyde dehydrogenase type 2 attenuates vasodilatory action of nitroglycerin in human veins. FASEB J. 2008; Feb 13.
  9. Sheikh AY, Schrepfer S, Stein W, West J, Lombard J, Burdon T, Pinsker B, Pelletier MP. Right atrial mass after primary repair of an atrial septal defect: thrombus masquerading as a myxoma. Ann Thorac Surg. 2007 Nov;84(5):1742-4.
  10. Schrepfer S, Deuse T, Reichenspurner H, Hoffmann J, Haddad M, Fischbein MP, Robbins RC, Pelletier MP. Effect of inhaled tacrolimus on cellular and humoral rejection to prevent posttransplant obliterative airway disease. Am J Transplant. 2007;7:1733–1742.
  11. Schrepfer S, Deuse T, Reichenspurner H, Hoyt G, Fischbein MP, Robbins RC, Pelletier MP. Techniques for experimental heterotopic and orthotopic tracheal transplantations – When to use which model? Transpl Immunol. 2007;17(4):255-261.
  12. Schrepfer S, Deuse T, Reichenspurner H, Fischbein MP, Robbins RC, Pelletier MP. Stem cell transplantation: The lung barrier. Transplant Proc. 2007;39(2):573-6.
  13. Schrepfer S, Deuse T, Pelletier MP, Fischbein MP, Robbins RC, Reichenspurner H. Is the malononitrilamide FK778 better for the prevention of acute or chronic rejection? Transplant Proc. 2007;39(2):569-72.
  14. Schrepfer S, Deuse T, Lange C, Katzenberg R, Reichenspurner H, Robbins RC, Pelletier MP. Simplyfied protocol to isolate, purify, and culture expand mesenchymal stem cells. Stem Cell Dev 2007;16(1):105-7.
  15. Schrepfer S, Deuse T, Hoyt G, Sheikh AY, Hoffmann J, Reichenspurner H, Robbins RC, Pelletier MP. Experimental orthotopic tracheal transplantation: The Stanford technique. Microsurgery. 2007;27(3):187-9.
  16. Sydow K, Schrepfer S, Franzen O, Detter C, Willems S, Meinertz T, Reichenspurner H. Coincidence of aortic valve stenosis and regurgitation and multiple cardiac papillary fibroelastomas in a young male adult. J Thorac Cardiovasc Surg. 2007;133(2):564-5.
  17. Schrepfer S, Deuse T,  Koch-Nolte F, Krieger T, Haddad M, Schäfer H, Pelletier MP, Robbins RC,; Reichenspurner H. FK778 in experimental xenotransplantation – A detailed analysis of drug efficacy. J Heart Lung Transplant. 2007;26(1):70-7.
  18. Schrepfer S, Deuse T, Sultan K, Münzel T, Schäfer H, Pelletier MP, Robbins RC, Reichenspurner H. Restenosis development after mechanical injury: A new field of application for Malononitrilamides? Cardiology. 2006;108(2):128-137.
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