Biological and Biomedical Science
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Joyce Bischoff

Department of Surgery, Vascular Biology Program
Children's Hospital
Karp Building, Room 12.212
One Blackfan Circle
Boston, MA 02115
Tel: (617) 919-2192
Fax: (617) 730-0231
Email: joyce.bischoff@childrens.harvard.edu

My laboratory is focused on endothelial progenitor cells (EPCs) and how they become disrupted in disease, and also how normal healthy EPCs might be used in regenerative medicine. 

Project I:  Cellular and Molecular Basis of Hemangioma

Hemangioma is a tumor of endothelial cells that occurs in infants.   These tumors can grow rapidly, cause organ damage and disfigurement and even threaten life.   A fascinating aspect is that all true hemangiomas regress, beginning after one year of age.  We are elucidating the cellular and molecular mechanisms that drive this uncontrolled growth and the spontaneous regression.   Our recent studies show that hemangiomas arise from a stem cell with properties of a primitive EPC.  Our ultimate goal is to identify the molecular basis of hemangioma, determine the mechanism(s) by which the molecular defect disrupts normal endothelial growth and differentiation, and to translate this knowledge into safe fast-acting therapies that will stop hemangiomas from growing to a life-threatening or endangering size.  

Project II:  Using Blood-derived Endothelial Progenitors for Tissue Vascularization

Our goal is to build vascular networks from human EPCs and mesenchymal progenitor cells (MPCs) to re-build damaged tissues and organs.  We and others have shown that human EPCs can be obtained from blood and expanded in the laboratory without difficulty.  We showed that EPCs combined with mature human smooth muscle cells could be used to build vascular networks in vivo in immune-deficient mice.  Our next goal is to identify as source of cells that can substitute for the mature smooth muscle cells, ideally a mesenchymal progenitor cell (MPC) that could be obtained from a patient by a minimally invasive procedure. In the future, we envision use of a patient’s own EPCs and MPCs to build vascular networks in tissue-engineering applications and for in situ regeneration of vascular networks in ischemic tissue. 

Project III: Endothelial Cell Growth and Differentiation in Semilunar Heart Valves

Towards a goal of creating tissue-engineered heart valves for children with congenital heart defects, 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.  Recently, we have identified valvular progenitor cells with endothelial/mesenchymal plasticity. We speculate that normal EPCs from cord blood can be expanded ex vivo and induced to behave as valve endothelial cells and thereby manipulated, via tissue engineering processes, to create viable long-lived tissue valve substitutes. 

 

References:

  • Paruchuri S, Yang J-H, Aikawa E, Melero-Martin JM, Khan ZA, Loukogeorgakis S, Schoen FJ, Bischoff J. 2006; Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to VEGF-A and TGFβ2. Circulation Research, 99: 861-869

  • Wu X, Lensch MW, Wylie-Sears J, Daley GQ, Bischoff J. 2007; Hemogenic endothelial progenitors cells isolated from human umbilical cord blood. Stem Cells, 25: 2770-2776.

  • Khan ZA, Boscolo E, Picard A, Psutka S, Melero-Martin JM, Bartch TC, Mulliken JB, Bischoff J. 2008, Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice, J. Clinical Investigation in press

  • Melero-Martin JM, De Obaldia ME, Kang S-Y, Khan ZA, Yuan L, Oettgen P, Bischoff J. 2008; Engineering vascular networks in vivo with human postnatal progenitor cells isolated from blood and bone marrow, Circulation Research, in press