Vericel Corporation · NASDAQ:VCEL
Vericel — Technical Presentation (May 2013)
13 slides from Vericel's technical presentation, May 2013
Slide 1: Potential Atheroprotective Effects of Ixmyelocel-T Cellular Therapy
Potential Atheroprotective Effects of Ixmyelocel-T Cellular Therapy Kelly J. Ledford, Nikki Murphy, Frank Zeigler, Ronnda L. Bartel 1
Slide 2: Ixmyelocel-T contains a M2-like population of macrophages
Ixmyelocel-T, an expanded, autologous multicellular therapy cultured from bone marrow mononuclear cells, contains a M2-like population of macrophages Alternatively activated macrophages (M2 macrophages) promote the resolution of inflammation by secreting anti- inflammatory cytokines and removing tis
Slide 3: Atherosclerosis is a multi-factorial disease of the vessel wall
Atherosclerosis is a multi-factorial disease of the vessel wall Libby P. Nature 420, 868-874(19 December 2002) Atherosclerosis is complex disease involving several different factors including: • Chronic Inflammation • Cellular Death • Lipid Accumulation An ideal therapy should address all components
Slide 4: Atherosclerosis - Role of the Macrophage
Atherosclerosis- Role of the Macrophage Macrophages are a key cell type involved in atherosclerosis-lipid accumulation, inflammation, efferocytosis Efferocytosis- • In early atherosclerotic lesions- macrophages remove dying foam cells, decreased plaque progression. In advanced lesions, macrophages d
Slide 5: Macrophages Secrete Anti-Inflammatory Cytokines
Ixmyelocel-T Macrophages Secretes Anti- Inflammatory Cytokines 45000 40000 * Cytokine Secretion (pg/mL) 35000 30000 25000 Basal 20000 +LPS 15000 10000 5000 0 * IL-10 IL-1ra TNFα IL-1β IL-12 IL-10, IL-r1a, TNFα, IL-1β, and IL-12 were quantified in MACS sorted CD14+ sorted ixmyelocel-T supernatants tr
Slide 6: Macrophages Express Surface Receptors of Alternative Activation and Scavenger Receptors
Ixmyelocel-T Macrophages Express Surface Receptors of Alternative Activation and Scavenger Receptors Involved in Lipid and Apoptotic Cell Uptake Flow cytometry revealed that ixmyelocel-T macrophages express surface receptors of alternative activation, CD206 and CD163, and scavenger receptors involve
Slide 7: Efferocytosis: Alternatively activated macrophages phagocytize apoptotic cells
Efferocytosis: Ixmyelocel-T alternatively activated macrophages readily phagocytize apoptotic cells ixmyelocel-T + 70 60 * ixmyelocel-T Apoptotic Cells Apoptotic Cells Enlarged Cell Percentage (%) 50 40 30 20 10 0 CD14 CD14 + Apoptotic Cells ixmyelocel-T + PKH26 ixmyelocel-T PKH26 Apoptotic Cells Ap
Slide 8: Reduced Scavenger Receptor Expression
Ixmyelocel-T Macrophages as less likely to become overladen with modified lipids- Reduced Scavenger Receptor Expression THP-1 IXT 1.4 CD36 (Fold Change) 1.2 1 0.8 -Ac-LDL 0.6 +Ac-LDL 0.4 0.2 0 ** THP-1 IXT 2 Fluorescent microscopy images of ixmyelocel-T and THP-1 SCARB1 (Fold Change) macrophages loa
Slide 9: Not sensitive to modified cholesterol-induced lipotoxicity
Ixmyelocel-T is not sensitive to modified cholesterol-induced lipotoxicity 140 Apoptosis (Relative to Control) 120 * 100 80 -AcLDL 60 +AcLDL 40 20 0 THP-1 IXT To determine if lipid loading resulted in apoptosis, both ixmyelocel-T and THP-1 macrophages were loaded with 100 μg/mL Ac-LDL for 24 hours.
Slide 10: Enhanced Cholesterol Efflux Capacity - Cholesterol Transport Genes
Ixmyelocel-T Macrophages Display Enhanced Cholesterol Efflux Capacity- Cholesterol Transport Genes Quantitative real-time PCR gene expression analysis of scavenger receptors normalized to GAPDH, the relative control (n > 5). Expression of ABCA1, ABCG1, ACAT1, and CEH in THP-1 and ixmyelocel-T macrop
Slide 11: Displays Enhanced Cholesterol Efflux Capacity
Ixmyelocel-T Displays Enhanced Cholesterol Efflux Capacity 18 16 ** 14 Cholesterol Efflux (%) 12 10 THP-1 8 ixmyelocel-T 6 4 * 2 0 ApoA-I HDL3 The ability of ixmyelocel-T to efflux cholesterol was measured with an in vitro cholesterol efflux assay. Ixmyelocel-T and THP-1 cells were loaded with free
Slide 12: Effluxes Cholesterol In Vivo (Reverse Cholesterol Transport Assay)
Ixmyelocel-T Effluxes Cholesterol In Vivo (Reverse Cholesterol Transport Assay) 4.5 4 3.5 (% injected cpm) RCt to Serum 3 2.5 2 J774 1.5 IXT 1 0.5 0 0 24 48 Reverse cholesterol transport comprises Time (hrs) all the different steps in cholesterol metabolism between cholesterol efflux 7 6 from macrop
Slide 13: Collectively this data suggests ixmyelocel-T therapy might be beneficial for atherosclerotic diseases
Collectively this data suggests ixmyelocel-T therapy might be beneficial for the treatment of atherosclerotic diseases • Immunomodulation: Anti-inflammatory cytokine secretion Libby P. Nature 420, 868-874(19 December 2002) • Tissue Remodeling/Phagocytosis of necrotic tissue • Modified Cholesterol Up