04b_duda - BMDCs and Cancer Therapy BMDCs and Cancer...

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Unformatted text preview: BMDCs and Cancer Therapy BMDCs and Cancer Therapy 1. 1. BMDCs for cell-based therapies BMDCs for cell-based therapies Harvard-MIT Division of Health Sciences and Technology HST.525J: Tumor Pathophysiology and Transport Phenomena, Fall 2005 Course Director: Dr. Rakesh Jain Engineered embryonic Engineered embryonic EPCs EPCs for tumor targeting for tumor targeting See: Fig. 1 and 8 in Wei, et al. "Embryonic endothelial progenitor cells armed with a suicide gene target hypoxic lung metastases Images removed for copyright reasons. after intravenous delivery." Cancer Cell 5 (2004): 477-488. Homing kinetics after cell infusion Homing kinetics after cell infusion Cell homing after a lineage negative cell delivery, local and systemic, Cell homing after a lineage negative cell delivery, local and systemic, in tumor bearing mice (mammary carcinoma in CW) in tumor bearing mice (mammary carcinoma in CW) 10 minutes, x20, MPLSM 10 minutes, x20, MPLSM 90 minutes, x6.25, IVM 90 minutes, x6.25, IVM Images removed for copyright reasons. Courtesy of Nature Publishing Group. Source: Stroh, M., J. P. Zimmer, D. G. Duda, T. S. Levchenko, K. S. Cohen, E. B. Brown, D. T. Scadden, V. P. Torchilin, M. G. Bawendi, D. Fukumura, and R. K. Jain. "Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo." Nature Medicine 11 (2005): 678-682. Cell cytoplasm labeling using Cell cytoplasm labeling using Quantum dots micelle and tat Quantum dots micelle and tat bioconjugate bioconjugate 2-photon image of Q-dots labeled progenitor cells (red) 2-photon image of Q-dots labeled progenitor cells (red) Vessel enhancement by Q-dots (blue) infusion Vessel enhancement by Q-dots (blue) infusion Mammary carcinoma Mammary carcinoma in CW in CW 100m 100m Courtesy of Nature Publishing Group. Source: Stroh, M., J. P. Zimmer, D. G. Duda, T. S. Levchenko, K. S. Cohen, E. B. Brown, D. T. Scadden, V. P. Torchilin, M. G. Bawendi, D. Fukumura D, R. K. Jain "Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo." Nature Medicine 11 (2005): 678-682. 2. 2. Role of BMDCs in tumor relapse after Role of BMDCs in tumor relapse after treatment reatment BMDC targeting delays tumor growth BMDC targeting delays tumor growth 500 400 300 200 100 0 0 2 4 6 8 10 12 DAYS SURFACE AREA (mm 2 ) WT (5) WT + mF - 1 (5) WT + DC 101 (5) WT + mF - 1/DC 101 (5) Neutralizing the BMDCs with antibodies to both murine VEGFR1 (mF-1) and VEGFR2 (DC101) blocks tumor angiogenesis and thus blocks tumor growth. Figure by MIT OCW. Images removed for copyright reasons. See: Fig. 6 in Lyden, Rafii et al. "Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth." Nature Medicine 7 (2001): 1194 - 1201. Tumor response to radiation is BMDC-dependent Tumor response to radiation is BMDC-dependent Asmase +/+ Asmase -/- Apoptotic Endothelial Cells per field (X400) 20 15 5 10 0 0 4 8 10 24 Time after radiation (hours)...
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04b_duda - BMDCs and Cancer Therapy BMDCs and Cancer...

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