Summary
of Research Projects
Characterization of the Facilitating
Cell
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.
Partial Conditioning and Recipient Space
We are working to develop partial (and therefore, less toxic) conditioning strategies for the establishment of mixed chimerism. What are the cells in the recipient "space," or microenvironment, that prevent engraftment, and how can we best target these cells?
Diabetes and Autoimmunity
Through the use of a non-obese diabetic mouse model, we are working to establish mixed chimerism as a means of reducing the risks associated with bone marrow transplantation for the treatment of autoimmune diseases.
Professional Bio
| 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
Rezzoug F, Huang Y, Tanner MK, Wysoczynski M, Schanie CL, Chilton PM, Ratajczak MZ, Fugier-Vivier IJ, Ildstad ST.
TNF-alpha is critical to facilitate hemopoietic stem cell engraftment and function.
J Immunol. 2008 Jan 1;180(1):49-57.
PMID: 18097003
Adamson LA, Huang WC, Breidenbach WC, Rahhal D, Xu H, Huang Y, Pidwell DJ, Wei FC, Tobin G, Ildstad ST.
A modified model of hindlimb osteomyocutaneous flap for the study of tolerance to composite tissue allografts.
Microsurgery. 2007;27(7):630-6.
http://www.ncbi.nlm.nih.gov/sites/entrez/17868137
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. 2007 Sep 7;
http://www.ncbi.nlm.nih.gov/sites/entrez/17827394
Li Y, Atmaca-Sonmez P, Schanie CL, Ildstad ST, Kaplan HJ, Enzmann V.
Endogenous bone marrow derived cells express retinal pigment epithelium cell markers and migrate to focal areas of RPE damage.
Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4321-7.
http://www.ncbi.nlm.nih.gov/sites/entrez/17724223
Xu H, Chilton PM, Huang Y, Schanie CL, Yan J, Ildstad ST.
Addition of cyclophosphamide to T-cell depletion-based nonmyeloablative conditioning allows donor T-cell engraftment and clonal deletion of alloreactive host T-cells after bone marrow transplantation.
Transplantation. 2007 Apr 15;83(7):954-63.
http://www.ncbi.nlm.nih.gov/sites/entrez/17460568
Tobin GR, Breidenbach WC 3rd, Pidwell DJ, Ildstad ST, Ravindra KV.
Transplantation of the hand, face, and composite structures: evolution and current status.
Clin Plast Surg. 2007 Apr;34(2):271-8, ix-x. Review.
http://www.ncbi.nlm.nih.gov/sites/entrez/17418676
Facilitating cells: novel promoters of stem cell alloengraftment and donor-specific transplantation tolerance in the absence of GVHD.
Crit Rev Oncol Hematol. 2007 Jan;61(1):26-43. Epub 2006 Dec 5. Review.
http://www.ncbi.nlm.nih.gov/sites/entrez/17150368
Atmaca-Sonmez P, Li Y, Yamauchi Y, Schanie CL, Ildstad ST, Kaplan HJ, Enzmann V. Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE-65 in a mouse model of retinal pigment epithelium damage.
Exp Eye Res. 2006 Nov;83(5):1295-302. Epub 2006 Sep 1.
http://www.ncbi.nlm.nih.gov/sites/entrez/16949576
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 Nov 15;108(10):3611-9. Epub 2006 Aug 3.
http://www.ncbi.nlm.nih.gov/sites/entrez/16888094
Huang Y, Kucia M, Rezzoug F, Ratajczak J, Tanner MK, Ratajczak MZ, Schanie CL, Xu H, Fugier-Vivier I, 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 Apr;24(4):936-48.
http://www.ncbi.nlm.nih.gov/sites/entrez/16644924
Li Y, Reca RG, Atmaca-Sonmez P, Ratajczak MZ, Ildstad ST, Kaplan HJ, Enzmann V.
Retinal pigment epithelium damage enhances expression of chemoattractants and migration of bone marrow-derived stem cells.
Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1646-52.
http://www.ncbi.nlm.nih.gov/sites/entrez/16565405
Dawn B, Guo Y, Rezazadeh A, Huang Y, Stein AB, Hunt G, Tiwari S, Varma J, Gu Y, Prabhu SD, Kajstura J, Anversa P, Ildstad ST, Bolli R.
Postinfarct cytokine therapy regenerates cardiac tissue and improves left ventricular function.
Circ Res. 2006 Apr 28;98(8):1098-105. Epub 2006 Mar 23.
http://www.ncbi.nlm.nih.gov/sites/entrez/16556872
Kucia M, Zhang YP, Reca R, Wysoczynski M, Machalinski B, Majka M, Ildstad ST, Ratajczak J, Shields CB, Ratajczak MZ.
Cells enriched in markers of neural tissue-committed stem cells reside in the bone marrow and are mobilized into the peripheral blood following stroke.
Leukemia. 2006 Jan;20(1):18-28.
http://www.ncbi.nlm.nih.gov/sites/entrez/16270036
Huang Y, Rezzoug F, Xu H, Chilton PM, Schanie CL, Fugier-Vivier I, Ildstad ST.
NK cells play a critical role in the regulation of class I-deficient hemopoietic stem cell engraftment: evidence for NK tolerance correlates with receptor editing.
J Immunol. 2005 Sep 15;175(6):3753-61.
http://www.ncbi.nlm.nih.gov/sites/entrez/16148121
Fugier-Vivier IJ, Rezzoug F, Huang Y, Graul-Layman AJ, Schanie CL, Xu H, Chilton PM, Ildstad ST.
Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment.
J Exp Med. 2005 Feb 7;201(3):373-83.
http://www.ncbi.nlm.nih.gov/sites/entrez/15699072
Michaels MG, Kaufman C, Volberding PA, Gupta P, Switzer WM, Heneine W, Sandstrom P, Kaplan L, Swift P, Damon L, Ildstad ST.
Baboon bone-marrow xenotransplant in a patient with advanced HIV disease: case report and 8-year follow-up.
Transplantation. 2004 Dec 15;78(11):1582-9.
http://www.ncbi.nlm.nih.gov/sites/entrez/15591945
Kucia M, Dawn B, Hunt G, Guo Y, Wysoczynski M, Majka M, Ratajczak J, Rezzoug F, Ildstad ST, Bolli R, Ratajczak MZ.
Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction.
Circ Res. 2004 Dec 10;95(12):1191-9. Epub 2004 Nov 18.
http://www.ncbi.nlm.nih.gov/sites/entrez/15550692
Xu H, Exner BG, Chilton PM, Schanie C, Ildstad ST.
CD45 congenic bone marrow transplantation: evidence for T cell-mediated immunity.
Stem Cells. 2004;22(6):1039-48.
http://www.ncbi.nlm.nih.gov/sites/entrez/15536194
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 Mar 1;105(5):2189-97.
http://www.ncbi.nlm.nih.gov/sites/entrez/15522953
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