04a_duda - Contribution of bone marrow-derived cells...

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Unformatted text preview: Contribution of bone marrow-derived cells Contribution of bone marrow-derived cells during tumor progression during tumor progression and treatment and treatment Dan G Duda, DMD, PhD Dan G Duda, DMD, PhD Steele Laboratory Steele Laboratory Massachusetts General Hospital Massachusetts General Hospital Harvard Medical School Harvard Medical School Reference: Harvard-MIT Division of Health Sciences and Technology HST.525J: Tumor Pathophysiology and Transport Phenomena, Fall 2005 Course Director: Dr. Rakesh Jain 1. In In troduction: S : S tem cells and neovascularization 2. BMDCs involvement in neovascularization during tumor growth tumor growth 3. BMDCs andthe therapy of cancer Embryonic stem cells Embryonic stem cells Vasculogenesis Vasculogenesis l Blastocyst Fetus Inner Cell Mass Trophob ast In Vitro Fertilization Totipotent Cells Figure by MIT OCW. Blood Stem Cells Red Blood Cells Specialized Cells White Blood Cells Platelets Other Committed Stem Cells Pluripotent Stem Cell Totipotent Cells Figure by MIT OCW. Courtesy of the National Institutes of Health. Vasculogenesis in Embryo Vasculogenesis in Embryo Undifferentiated Cells "Vascular Progenitor Cells" E-cadherin + E-cadherin- Flk1 + Flk1 + Flk1 + Flk1- Flk1- VEGF VEGF ? Hemangioblast? PDGF-BB Mesenchymal Stem Cells? Other Lineage Blood Cells EC MC PDGF- R + SM-tropomyosin + Desmin + SMA + Flk1- CD45 + Ter119 + VE-cadherin + PECAM1 + CD34 + Endoglin + Blood Vessels Figure by MIT OCW. After Yamashita et al., 2000. Endothelial Progenitors Blood Cells Skeletal Muscle Haemangioblast Angioblast Pre-venous Angioblast Pre-arterial Angioblast VEGF VEGF VEGF Endothelial Cells Arterial Endothelial Cells PDGF-BB PDGF-BB PDGF-BB Smooth Muscle Cells Pericytes Progenitors Cells Others? Progenitor Expressing PDGF Receptor- Mesenchymal Cell Neural Crest Cell Epicardial-derived Cell Smooth Muscle Progenitors After Carmeliet, 2001. Venous Blood Vessel Common Vascular Vascular Progenitor Figure by MIT OCW. Image removed for copyright reasons. for Hematopoietic Stem Cells in Promoting Angiogenesis." Cell 102, no. 2 (2000): 199-209. Source: Takakura, Nobuyuki, Toshio Watanabe, Souichi Suenobu, Yoshihiro Yamada, Tetsuo Noda, Yoshiaki Ito, Masanobu Satake, and Toshio Suda. "A Role Adult stem cells Adult stem cells Vasculogenesis Vasculogenesis Adult Adult Hematopoiesis Hematopoiesis Image removed for copyright reasons. Stem Cell Sorting Stem Cell Sorting (CD3, CD4, CD8, CD45, (CD3, CD4, CD8, CD45, Gr-1, Mac-1, B220, and TER-119) Gr-1, Mac-1, B220, and TER-119) BM Harvest Magnetic Selection Clone-sorting Microscopic Examination Transplantation Figure by MIT OCW . Hematopietic stem cells assays Hematopietic stem cells assays Self-Renewal Stemcell Transient amplifying cells Multi-lineage differentiation WBC XRT Functional repopulation A B C Figure by MIT OCW. B one Marrow Transp ROSA 26 (mouse transgenic for bacterial actosidase ) mouse transgenic for yFsh green Detection of GFP (fluorescence Detection of β-galactosidase...
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04a_duda - Contribution of bone marrow-derived cells...

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