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Suzanne T. Ildstad, M.D.

by Eaves JR,Baxter Slaten last modified Mar 05, 2014 10:50 AM

Suzanne T. Ildstad, M.D. 

Suzanne T. Ildstad, M.D.

Director, Institute for Cellular Therapeutics

Jewish Hospital Distinguished Professor of Transplantation

Distinguished University Scholar 

Professor of Surgery, Physiology, Immunology

CEO, Regenerex, LLC

Research Interests

Characterization of the Facilitating Cells
Facilitating cells enable the long-term, durable engraftment of hematopoietic stem cells across genetic barriers. How do these unique cells function, and what is their ontogeny?

The Sensitized State

Sensitized recipients are more prone to bone marrow and solid organ graft rejection. Mixed chimerism may reverse the immunologic memory and establish donor specific tolerance. How can we overcome immunologic memory barrier in sensitized recipient for successful bone marrow transplantation?

Nonmyeloablative Conditioning for bone marrow transplantation
We are working to develop nonmyeloablative (and therefore, less toxic) conditioning strategies for the establishment of mixed chimerism. What are the cells in the recipient microenvironment, that prevent engraftment, and how can we best target these cells and the pathways to suppress the function of these cells?

Diabetes and Autoimmunity
Through the use of a non-obese diabetic mouse model, we are working to establish mixed chimerism for the treatment of autoimmune diseases. 

 Professional Bio

2002-present       

CEO, Regenerex, LLC

1998-Present 

Director, Institute for Cellular Therapeutics, Jewish Hospital Distinguished Professor of Transplantation, Professor of Surgery, University of Louisville, Louisville, Kentucky

 1996 - 1998

Director, Institute for Cellular Therapeutics and Professor of Surgery, Department of Surgery, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania

 1995 - 1996

Professor and Chief, Division of Cellular Therapeutics, University of Pittsburgh

 1992 - 1995

Co-Director, Cell Transplant Facility, Division of Transplantation, University of Pittsburgh

 1992 - 1995

Associate Professor, Department of Surgery, University of Pittsburgh

 1988 - 1992

Assistant Professor (with tenure), Department of Surgery, University of Pittsburgh

 1986 - 1988

Clinical Fellow in Pediatric Surgery, Children's Hospital, Cincinnati

 1985 - 1986

 Resident, General Surgery, Massachusetts General Hospital, Boston

 1982 - 1985

 Medical Staff Fellow, National Institutes of Health, Immunology Branch, NCI

Publications

Goode I, Xu H, Ildstad ST.  Regulatory B Cells: the new “it” cell. Transplant Proc. 2013 Nov 8. pii: S0041-1345(13)00880-4.  http://www.ncbi.nlm.nih.gov/pubmed/24216174

 Xu H, Yan J, Zhu Z, Hussain L-R, Huang Y, Ding C, Bozulic LD, Wen Y, Ildstad ST.  A critical role for the TLR4/TRIF pathway in allogeneic hematopoietic cell rejection by innate immune cells.  Cell Transplant. 2013;22(12):2367-80.  http://www.ncbi.nlm.nih.gov/pubmed/23146386

  Xu H, Ramsey DM, Bozulic LD, Ildstad ST.  Simultaneous bone marrow and composite tissue transplantation in rats treated with nonmyeloablative conditioning promotes tolerance.  Transplantation 2013; 95(2):301-8. http://www.ncbi.nlm.nih.gov/pubmed/23250336

 Ravindra K, Leventhal J, Song D, Ildstad ST.  Chimerism and Tolerance in Solid Organ Transplantation.  Journal of Clinical and Cellular Immunology S9:003, 2012.  http://www.omicsonline.org/chimerism-and-tolerance-in-solid-organ-transplantation-2155-9899.S9-003.php?aid=9316

 Leventhal J, Miller J, Abecassis M, Tollerud DJ, Ildstad ST.  Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants:  the long road to tolerance.  Journal of Clinical Pharmacology and Therapeutics 2012; 93(1):36-45. http://www.ncbi.nlm.nih.gov/pubmed/23212110

Leventhal J, Abecassis M, Miller J, Gallon L, Tollerud D, King B, Elliott MJ, Bozulic LD, Houston C, Ildstad ST.  Tolerance induction in HLA disparate living donor kidney transplantation by donor stem cell infusion: durable chimerism predicts outcome.  Transplantation. 2013 Jan 15;95(1):169-76. http://www.ncbi.nlm.nih.gov/pubmed/23222893

 Ravindra KV, Xu H, Bozulic LD, Song DD, Ildstad ST.  The need for inducing tolerance in vascularized composite allotransplantation.  Clinical and Developmental Immunology 2012 Nov; 2012:1-11.  http://www.ncbi.nlm.nih.gov/pubmed/23251216

 Xu H, Ildstad ST.  Transplantation: Is donor T cell engraftment a biomarker for tolerance? Nature Reviews Nephrology 2012; Oct; 8(10):560-561. http://www.ncbi.nlm.nih.gov/pubmed/22868709

 Chen B, Xu H, Corbin DR, Ildstad ST.  A clinically feasible approach to induce delayed tolerance in recipients of prior kidney and vascular composite allotransplants. Transplantation 2012 Oct; 94(7):671-678.   http://www.ncbi.nlm.nih.gov/pubmed/22948444

 Leventhal J, Huang Y, Xu H, Goode I, Ildstad ST.  Novel regulatory therapies for treatment and prevention of GVHD.  BMC Medicine 2012 May; 10:48. http://www.ncbi.nlm.nih.gov/pubmed/22587383

 Pomahac B, Becker YT, Cendales L, Ildstad ST, Li X, Schneeberger S, Siemionow M, Thomson AW, Zheng XX, and S.G. Tullius.  Vascularized Composite Allotransplantation Research: The Emerging Field. A position paper of the American Society of Transplantation. American Journal of Transplantation 2012 Apr;12(4):1062-1063.  http://www.ncbi.nlm.nih.gov/pubmed/?term=Ildstad+St+Pomahac

 Ravindra K, Haeberle M, Levin LS, Ildstad ST.  Immunology of vascularized composite allotransplantation: a primer for hand surgeons.  The Journal of Hand Surgery 2012 Apr; 37(4):842-850. http://www.ncbi.nlm.nih.gov/pubmed/22464235

Xu H, Zhu Z, Huang Y, Bozulic LD, Hussain L-R, Yan J, Ildstad ST.  Innate and Adaptive Immune Responses Are Tolerized in Chimeras Prepared with Non-Myeloablative Conditioning. Transplantation 2012 Mar 15;93(5):469-76. http://www.ncbi.nlm.nih.gov/pubmed/22228418

Leventhal J, Abecassis M, Miller J. Gallon L, Ravindra K, Tollerud DJ, King B, Herzig G, Herzig R, Ildstad ST.  Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation.  Science Translational Medicine 2012 Mar 7; 4(124): 124ra28.  http://www.ncbi.nlm.nih.gov/pubmed/22399264

Guo Y, Sanganalmath SK, Wu W, Zhu X, Huang Y, Tan W, Ildstad ST, Li Q, Bolli R. Identification of inducible nitric oxide synthase in peripheral blood cells as a mediator of myocardial ischemia/reperfusion injury. Basic Research in Cardiology 2012;107(2):1-8. http://www.ncbi.nlm.nih.gov/pubmed/22351077

Ravindra K, Xu H, Ildstad ST.  Vascularized composite allotransplantation (VCA) at a cross roads.  Transplantation Proceedings 2011; 43(9):3501-3. http://www.ncbi.nlm.nih.gov/pubmed/22099829

Cardenas PA, Huang Y, Ildstad ST.  The role of pDC, recipient Treg, and donor Treg in HSC engraftment:  Mechanisms of Facilitation. Chimerism 2011; 2(3):65-70. Epub 2011 Jul 1.  http://www.ncbi.nlm.nih.gov/pubmed/22163063

Ravindra KV, Ildstad ST.  Immunosuppressive protocols and immunological challenges related to hand transplantation.  Hand Clinics 2011; 27:467-479. http://www.ncbi.nlm.nih.gov/pubmed/?term=Ildstad+St+Hand+Clinics+2011

Wu S, Xu H, Chen B, Wen Y, Ikusika OM, Ocker A, Zhao H, Ildstad ST.  Sensitized recipients exhibit accelerated but not hyperacute rejection of vascularized composite tissue allografts.  Transplantation 2011; 92(6):627-633.  http://www.ncbi.nlm.nih.gov/pubmed/21822173

 Bozulic LD, Huang Y, Xu Y, Wen Y, Ildstad ST.  Differential Outcomes in Pre-diabetic vs. Overtly Diabetic NOD Mice Nonmyeloablatively Conditioned with Co-stimulatory Blockade.  Experimental Hematology 2011; 39:977-985.  http://www.ncbi.nlm.nih.gov/pubmed/21726515

 Ildstad ST, Shirwan H, Leventhal J.  Is durable macrochimerism key to achieving clinical transplantation tolerance?  Curr Opin Organ Transplant. 2011 Aug;16(4): 343-4. http://www.ncbi.nlm.nih.gov/pubmed/?term=Ildstad+St+Shirwan+H%2C+Leventhal+J

 Bozulic LD, Wen Y, Xu H, Ildstad ST.  Evidence that FoxP3+ Treg may play a role in promoting long-term acceptance of CTA.  Transplantation, 2011; 91(8):908-915. http://www.ncbi.nlm.nih.gov/pubmed/21304439

 Huang Y, Bozulic LD, Miller T, Xu H, Hussain L-R, Ildstad ST.  CD8α+ plasmacytoid precursor DC induce antigen-specific regulatory T cells that enhance HSC engraftment in vivo.  Blood. 2011 Feb 24;117(8):2494-505.  http://www.ncbi.nlm.nih.gov/pubmed/21190989

 Wen Y, Chen Bo, Ildstad ST.  Stem cell-based strategies for the treatment of Type 1 diabetes mellitus. Expert Opinion on Biological Therapy, 2011: 11(1):41-53. http://www.ncbi.nlm.nih.gov/pubmed/21110785

 Huang Y, Enzmann V, Ildstad ST.  Stem cell-based therapeutic applications in retinal degenerative diseases.  Stem Cell Reviews and Reports, 2011; 7:434-445.  http://www.ncbi.nlm.nih.gov/pubmed/20859770

Huang Y, Ildstad ST.   A novel role of innate immune responses (TLR-4) in triggering GVHD. Transplantation, 2010; 90(10):1052-1053.  http://www.ncbi.nlm.nih.gov/pubmed/20844466

Xu H, Huang Y, Hussain L-R, Zhu Z, Bozulic LD, Yan J, Ildstad ST.  Sensitization to minor antigens is a significant barrier in transplantation and is prevented by CD154:CD40 blockade.  American Journal of Transplantation, 2010: 10(7):1569-1579. http://www.ncbi.nlm.nih.gov/pubmed/20642683

Huang Y, Kucia M, Hussain L-R, Wen Y, Xu H, Yan J, Ratajczak MZ, Ildstad ST. Bone marrow transplantation temporarily improves pancreatic function in streptozotocin-induced diabetes: potential involvement of VSEL cells.  Transplantation, 2010: 89(6):677-685.  http://www.ncbi.nlm.nih.gov/pubmed/20110858

Ding C, Cai Y, Marroquin J, Ildstad ST, Yan J.  Plasmacytoid dendritic cells regulate autoreactive B cell activation via soluble factors and in a cell-to-cell contact manner.  Journal of Immunology, 2009 Dec 1;183(11):7140-9. http://www.ncbi.nlm.nih.gov/pubmed/19890051

Rahhal DN, Xu H, Huang W-C, Wu S, Huang Y, Ildstad ST. Dissociation between peripheral blood chimerism and tolerance to hindlimb composite tissue transplants:  preferential localization of chimerism in donor bone.  Transplantation 2009: 88(6):773-81.  http://www.ncbi.nlm.nih.gov/pubmed/19920776

Sanganalmath SK,  Stein AB, Guo Y, Tiwari S, Hunt G, Vincent RJ, Huang Y, Rezazadeh A, Ildstad ST, Dawn B, Bolli R. The beneficial effects of postinfarct cytokine combination therapy are sustained during long-term follow-up.  Journal of Molecular and Cellular Cardiology 2009;47(4):528-35. http://www.ncbi.nlm.nih.gov/pubmed/19616005

Ravindra KV, Wu S, McKinney M, Xu H, Ildstad ST.  Composite tissue allotransplantation:  current challenges.  Transplantation Proceedings 2009; 41(9):3519-3528http://www.ncbi.nlm.nih.gov/pubmed/19917338

Enzmann V, Yolcu E, Kaplan HJ, Ildstad ST.  Stem cells as tools in regenerative therapy for retinal degeneration.  Archives of Ophthalmology 2009; 127(4):563-571. http://www.ncbi.nlm.nih.gov/pubmed/19365041

Tobin GR, Breidenbach WC, Ildstad ST, Marvin MM, Buell JF, and Ravindra KV.  The history of human composite tissue allotransplantation.  Transplantation Proceedings 2009; 41(2):466-71.  http://www.ncbi.nlm.nih.gov/pubmed/19328905

Wu S, Xu H, Ravindra K, Ildstad ST.  Composite Tissue Allotransplantation: Past, Present and Future – the History and Expanding Applications of CTA as a New Frontier in Transplantation. Transplantation Proceedings 2009; 41(2):463-5.  http://www.ncbi.nlm.nih.gov/pubmed/19328904

Xu H, Huang Y, Chilton PM, Hussain L-R, Tanner MK, Yan J, Ildstad ST.  Strategic nonmyeloablative conditioning:  CD154:CD40 co-stimulatory blockade at primary BMT promotes engraftment for secondary BMT after engraftment failure.  Journal of Immunology 2008; 181(9):6616-24.  http://www.ncbi.nlm.nih.gov/pubmed/18941252

Swearingen B, Ravindra K, Xu H, Wu S, Breidenbach WC, Ildstad ST.  The Science of Composite Tissue Allotransplantation.  Transplantation 2008; 86(5):627-635.  http://www.ncbi.nlm.nih.gov/pubmed/18791440

Huang Y, Fugier-Vivier IJ, Miller T, Elliott MJ, Xu H, Bozulic L, Chilton PM, Ildstad ST.  Plasmacytoid precursor dendritic cells from NOD mice exhibit impaired function:  are they a component of diabetes pathogenesis?  Diabetes 2008; 57(9):2360-70. http://www.ncbi.nlm.nih.gov/pubmed/18567821

 Huang Y, Ratajczak MZ, Reca R, Xu H, Tanner M, Rezzoug F, Hussain L-R, Fugier-Vivier I, Bolli R, Ildstad ST.  Fms-related tyronsine kinase 3 (Flt3) expression discriminates hematopoietic stem cells subpopulations with differing engraftment-potential: identifying the most potent combination.  Transplantation 2008; 85(8): 1175-1184.  http://www.ncbi.nlm.nih.gov/pubmed/18431239

 Ravindra KV, Wu S, Bozulic L, Xu H, Breidenbach WC, Ildstad ST. Composite Tissue Transplantation:  A Rapidly Advancing Field.  Transplantation Proceedings 2008; 40(5):1237-48. http://www.ncbi.nlm.nih.gov/pubmed/18589081

 Xu H, Yan J, Huang Y, Chilton PM, Ding C, Schanie CL, Wang L, Ildstad ST.  Co-stimulatory blockade of CD154:CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization.  Blood 2008; 111:3266-3275.  http://www.ncbi.nlm.nih.gov/pubmed/17827394

 Rezzoug F, Huang Y, Tanner MK, Wysoczynski M, Schanie CL, Chilton PM, Ratajczak MZ, Fugier-Vivier IJ, Ildstad ST.  TNFα is critical to facilitation of hematopoietic stem cell engraftment and function. Journal of Immunology 2008; 180:49-57. http://www.ncbi.nlm.nih.gov/pubmed/18097003

 Xu H, Chilton PM, Tanner MK, Huang Y, Schanie CL, Dy-Liacco M, Yan J, Ildstad ST.  Humoral immunity is the dominant barrier for allogeneic bone marrow engraftment in sensitized recipients.  Blood 2006; 108(10): 3611-3619.  http://www.ncbi.nlm.nih.gov/pubmed/16888094

 Huang Y, Kucia M, Rezzoug F, Ratajczak J, Tanner M, Ratajczak MZ, Schanie CL, Xu H, Fugier-Vivier IJ, Ildstad ST.  Flt3-ligand-mobilized peripheral blood, but not Flt3-ligand-expanded bone marrow, facilitating cells promote establishment of chimerism and tolerance.  Stem Cells 2006; 24: 936-948.  http://www.ncbi.nlm.nih.gov/pubmed/16644924

 Ildstad ST, Chilton PM, Xu H, Domenick MA, Kosiewicz MM, Ray MB.  Preconditioning of NOD mice with anti-CD8 mAb and co-stimulatory blockade enhances chimerism and tolerance and prevents diabetes while depletion of αβ-TCR+ and CD4+ cells negates the effect.  Blood 2005; 105: 2577-2584. http://www.ncbi.nlm.nih.gov/pubmed/15498851

Fugier-Vivier IJ, Rezzoug F, Huang Y,  Graul-Layman AJ , Schanie CL , Xu H, Chilton PM, Ildstad ST.  Plasmacytoid precursor dendritic cells play an integral role in facilitating allogeneic hematopoietic stem cell engraftment and tolerance induction.  Journal of Experimental Medicine 2005; 201(3):373-383.  http://www.ncbi.nlm.nih.gov/pubmed/15699072

Chilton PM, Rezzoug F, Ratajczak MZ, Fugier-Vivier I, Ratajczak J, Kucia M, Huang Y, Tanner MK, Ildstad ST.  Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients. Blood 2005; 105(5):2189-2197. http://www.ncbi.nlm.nih.gov/sites/entrez/15522953

Chilton PM, Rezzoug F, Fugier-Vivier I, Weeter LA, Xu H, Huang Y, Ray MB, Ildstad ST.  FLT-3 ligand treatment prevents diabetes in NOD mice. Diabetes 2004; 53(8):1995-2002. http://www.ncbi.nlm.nih.gov/pubmed/15277378

 Huang Y, Rezzoug F, Chilton PM, Grimes HL, Cramer DE, Ildstad ST.  Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells:  a role for host NK cells in regulating HSC engraftment.  Blood 2004; 104(3):873-880. http://www.ncbi.nlm.nih.gov/pubmed/15054040

 Yaroslavskiy B, Colson Y, Ildstad ST, Parrish D, Boggs SS.  Addition of a bone marrow “facilitating cell” population increases stem cell-derived cobblestone area formation in impaired long-term bone marrow culture stroma. Experimental Hematology 1998; 26:604-611. http://www.ncbi.nlm.nih.gov/pubmed/?term=Ildstad+St+Yaroslavskiy+B%2C+Colson+Y%2C

 Colson YL, Lange J, Fowler K, Ildstad ST.  Mechanism for co-tolerance in nonlethally conditioned mixed chimeras: Negative selection of the Vβ-T-cell receptor repertoire by both host and donor bone marrow-derived cells.  Blood 1996; 88(12):4601-4610. http://www.ncbi.nlm.nih.gov/pubmed/?term=Ildstad+St+Colson+YL%2C+Lange+J%2C+Fowler+K%2C

 Kaufman CL, Colson YL, Wren SM, Watkins S, Simmons RL, Ildstad ST.  Phenotypic characterization of a novel bone marrow derive- cell that facilitates engraftment of allogeneic bone marrow stem cells.  Blood 1994; 84(8):2436-2446. http://www.ncbi.nlm.nih.gov/pubmed/?term=Ildstad+St+Kaufman+CL%2C+Colson+YL%2C+Wren+SM%2C

Ildstad ST, Wren SM, Boggs SS, Hronakes ML, Vecchini F, Van den Brink MRM.  Cross species bone marrow transplantation:  Evidence for tolerance induction, stem cell engraftment, and maturation of T-lymphocytes in a xenogeneic stromal environment (rat → mouse).  Journal of Experimental Medicine 1991; 174:467-478. http://www.ncbi.nlm.nih.gov/pubmed/1856629

 Ildstad ST, Bluestone JA, Sachs DH.  Alloresistance to engraftment of allogeneic donor bone marrow is mediated by an Lyt2+ T cell in mixed allogeneic reconstitution (C57BL/10Sn + B10.D2/nSn → C56BL/10Sn).  Journal of Experimental Medicine 1986; 163:1343-1348. http://www.ncbi.nlm.nih.gov/pubmed/2939173

 Ildstad ST, Sachs DH.  Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts.  Nature 1984; 307:168-170.  http://www.ncbi.nlm.nih.gov/pubmed/6361574

 

 

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