My lab studies the role of Endothelial Cell Plasticity in Health and Diseases and in the normal repair of the vasculature. Here I describe the three major topics we are pursuing.
Infantile hemangioma is a vascular tumor that can grow rapidly, causing organ damage, disfigurement and morbidity. My lab has focused on the cellular mechanisms that drive this uncontrolled vascular growth. In 2001, we showed that hemangioma-derived endothelial cells are clonal and exhibit abnormal properties. This suggests that hemangiomas are initiated from a single abnormal progenitor cell. Since then we have isolated increasingly less differentiated cells from hemangioma tissue, which led us to the identification of a multi-potent stem cell that can recapitulate hemangioma in immune-deficient mice. Our goal is to use these stem cells and our animal model to identify new drugs that work safely and quickly to prevent hemangiomas from growing to an endangering size.
EPCs are a controversial area of research, in part because they are rare cells and are difficult to identify based on cellular markers. However, we have isolated and expanded endothelial cells with robust proliferative potential and vasculogenic activity in vivo from many different samples of human peripheral blood. We use these human EPCs combined with human mesenchymal progenitor cells, also isolated from blood or from bone marrow, to build stable, perfused vascular networks in vivo. Our goal is to build new vascular networks in ischemic tissues, and to analyze their contribution to tissue repair and regeneration.
We are also studying the plasticity of cardiac valve endothelium. We showed that valve endothelial cells from adult tissue can recapitulate processes that occur during valve development. We propose that valve endothelium harbors valvular endothelial progenitor cells that undergo an endothelial to mesenchymal transition to replenish the valve interstitial cells on an as-needed basis throughout adult life and possibly during valve disease.
About Joyce Bischoff
Joyce Bischoff received a doctorate in biochemistry from the Washington University School of Medicine and trained as a post-doctoral fellow at the Whitehead Institute for Biomedical Research. She joined the Surgical Research Laboratories at Children's Hospital in 1990.
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 Jr. Functional small diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2001 Sep; 7(9): 1035-40.
Yu Y, Flint A, Mulliken JB, Wu JK, Bischoff J. Endothelial progenitor cells in infantile hemangioma. Blood. 2004 Feb 15; 103(4): 1373-5.
Wu X, Rabkin-Aikawa E, Guleserian KJ, Perry TE, Masuda Y, Sutherland FW, Schoen FJ, Mayer JE Jr, Bischoff J. Tissue-engineered microvessels on three-dimensional biodegradable scaffolds using human endothelial cell progenitor cells. Am J Physiol Heart Circ Physiol. 2004 Aug; 287(2):H480-7.
Paruchuri S, Yang J-H, 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 VEGF-A and TGF_2. Circulation Research. 2006 Oct 13; 99(8): 861-9.
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.
Khan ZA, Boscolo E, Picard A, Psutka S, Melero-Martin JM, Bartch TC, Mulliken JB, Bischoff J. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J. Clin Invest. 2008 Jul; 118(7): 2592-9.
Melero-Martin JM, De Obaldia ME, Kang SY, Khan ZA, Yuan L, Oettgen P, Bischoff J. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circulation Research. 2008 Jul 18; 103(2): 194-202.
Bioengineered human vascular networks transplanted into secondary mice reconnect with the host vasculature and re-establish perfusion.
Kang KT, Allen P, Bischoff J.
Blood. 2011; 118(25): 6718-21.
E-selectin mediates stem cell adhesion and formation of blood vessels in a murine model of infantile hemangioma.
Smadja DM, Mulliken JB, Bischoff J.
Am J Pathol. 2012 Dec;181(6):2239-47 Epub 2012 Oct 4.
?6-integrin is required for the adhesion and vasculogenic potential of hemangioma stem cells.
Smadja DM, Guerin CL, Boscolo E, Bieche I, Mulliken JB, Bischoff J.
Stem Cells. 2013 Sep 10. [Epub ahead of print]
- Rapid onset of perfused blood vessels after implantation of ECFCs and MPCs in collagen, PuraMatrix and fibrin provisional matrices.
Allen P, Kang KT, Bischoff J.
J Tissue Eng Regen Med. 2013 Aug 16. [Epub ahead of print]
- Pathogenesis of infantile haemangioma.
Greenberger S, Bischoff J.
Br J Dermatol. 2013 Jul;169(1):12-9.
- Human vasculogenic cells form functional blood vessels and mitigate adverse remodeling after ischemia reperfusion injury in rats.
Kang KT, Coggins M, Xiao C, Rosenzweig A, Bischoff J.
Angiogenesis. 2013 Oct;16(4):773-84.
- miR-21 represses Pdcd4 during cardiac valvulogenesis.
Kolpa HJ, Peal DS, Lynch SN, Giokas AC, Ghatak S, Misra S, Norris RA, Macrae CA, Markwald RR, Ellinor P, Bischoff J, Milan DJ.
Development. 2013 May;140(10):2172-80.
- Pericytes from infantile hemangioma display proangiogenic properties and dysregulated angiopoietin-1.
Boscolo E, Mulliken JB, Bischoff J.
Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):501-9.