DF/HCC Program Affiliation

Member, Invasion, Metastasis, and Angiogenesis Program

Research Abstract

Hemangioma is a tumor of endothelial cells that occurs in infants. These tumors can grow rapidly, causing organ damage and disfigurement and even threatening life. However, a fascinating aspect is that hemangiomas regress over the course of several years, beginning at one year of age. In my laboratory, we are elucidating the cellular and molecular mechanisms that drive this uncontrolled growth and the spontaneous regression. Recently, we identified endothelial progenitor cells in proliferating hemangiomas – the first demonstration of these cells in a human vascular tumor. We are also working on how normal endothelial progenitors in blood might be used for cardiovascular repair and tissue-engineering. In a sheep model, we showed that autologous endothelial progenitor cells can be isolated from 15-20 milliliters of peripheral blood and used to create small diameter blood vessels. We also envision the use of blood-derived endothelial progenitors to repair or replace cardiac valves. To pursue this, we are studying growth and differentiation pathways in normal cardiac valve endothelium. Two of our studies have shown that valve endothelial cells from adult tissue can recapitulate processes that occur during valve development. These pathways involve TGF-β and VEGF signaling. We hypothesize that endothelial progenitors, expanded ex vivo, can be induced to behave as valve endothelial cells and thereby manipulated, via tissue engineering processes, to create viable long-lived tissue valve substitutes.

Publications

• Melero-Martin JM, Khan ZA, Picard A, Wu X, Paruchuri S, Bischoff J. In vivo vasculogenic potential of human blood-derived endothelial progenitor cells. Blood 2007 Jun 1; 109(11):4761-8
  PMID: 17327403
• Paruchuri S, Yang JH, Aikawa E, Melero-Martin JM, Khan ZA, Loukogeorgakis S, Schoen FJ, Bischoff J. Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to vascular endothelial growth factor-A and transforming growth factor-beta2. Circ Res 2006 Oct 13; 99(8):861-9
  PMID: 16973908
• Khan ZA, Melero-Martin JM, Wu X, Paruchuri S, Boscolo E, Mulliken JB, Bischoff J. Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin. Blood 2006 Aug 1; 108(3):915-21
  PMID: 16861344
• Yu Y, Flint AF, Mulliken JB, Wu JK, Bischoff J. Endothelial progenitor cells in infantile hemangioma. Blood 2004 Feb 15; 103(4):1373-5
  PMID: 14576053
• Kaushal S, Amiel GE, Guleserian KJ, Shapira OM, Perry T, Sutherland FW, Rabkin E, Moran AM, Schoen FJ, Atala A, Soker S, Bischoff J, Mayer JE. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med 2001 Sep; 7(9):1035-40
  PMID: 11533707
• Boye E, Yu Y, Paranya G, Mulliken JB, Olsen BR, Bischoff J. Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest 2001 Mar; 107(6):745-52
  PMID: 11254674