1. Current Trends in Cell Therapy Alexey Bersenev, MD, PhD Children’s Hospital of Philadelphia www.Hematopoiesis.info www.StemCellAssays.com twitter: @cells_nnm Moscow, Sep. 27, 2010 under the following license Creative Commons Atribution Non-Commercial
2. personal communication (Lab, conference) blog professional networking online discussion personal filters RSS PubMed journals blogs news reference managers collaborative filters groups on LinkedIn rooms on FriendFeed shared Google Waves faculty of 1000 shared references collaborative blogs … new real connections and collaboration shared posts (Twitter/ LinkedIn) networking with other bloggers Trending is information processing Bersenev A. Cellular Therapy and Transplantation. 2010;2(7). 10.3205/ctt-2010-en-000084.01
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4. Cancer Cell proliferation Stem cell self-renewal HSC aging Arf Ink4a Bmi-1 Hmga2 Sean Morrison group 2005-2008 Link between stem cell renewal, cancer and aging
8. Two ongoing clinical trials for cord blood HSC expansion: 1. Fred Hutchinson Cancer Center (Irwing Bernstein group. Nat Med 2010; 16:232 ) Set up: CB isolated CD34+ cultured on immobilized engineered Notch ligand in SCF /Flt3L /TPO /IL-3 /IL-6 for 16 days 2. MD Anderson Cancer Center (Elizabeth Shpall group. Reported at ASH and other conferences 2008-2010) Set up: CB isolated CD34+ or CD133+ in liquid culture in SCF /Flt3L /G-CSF /TPO for 2 weeks Co-culture with allogeneic related matched MSC or commercially available MSCs (Angioblast)
9. Expanded versus unmanipulated human cord blood samples neutrophils engraftment kinetics Adapted from Elizabeth Shpall report at 10th Anniversary of Netcord Conference16-19 October 2008 - Mandelieu, France (modified) time after transplant hematopoietic contribution one year
10. Lin- CD34+ CD38- CD90+ CD45RA- CD34+ CD38- CD90- CD45RA+ HSC MLP ETP B/NK CMP CD34+ CD38+ CD10+ CD45RA+ CD34+ CD38+ Flt3+ CD45RA- GMP MEP CD34+ CD38+ Flt3+ CD45RA+ CD34+ CD38+ Flt3- CD45RA- MDP MPP Lin- CD34+ CD38- CD90- CD45RA- Current map of human hematopoietic CD34+ population Irv Weissman group Cell Stem Cell 2007; 1: 635 John Dick group Nat Immunol 2010; 11: 585 stem cell (<10% of CD34+ in bone marrow and 0.5-1% of CD34+ in cord blood) progenitors (90-99% of CD34+) CD34+ ex vivo expansion possibility
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24. The place of cell therapy in Regen industry cell bio scaffold gene protein Regen /Cell Tx Biotech healthcare industry Pharma biologic Small molecule tissue chemical RNAi Regenerative Medicine replaces or regenerate human cells, tissue or organs, to restore or establish normal function (Chris Mason, 2008) cell therapy tissue engineering scaffold /biomatrix gene therapy growth factors /proteins Medical Device polymerscaffold micro RNA
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30. http://celltherapyblog.blogspot.com/2009/02/how-many-cell-therapy-products-are-in.html Cell products in development and on the market: Number of cell products in different phases of development: 78 Pre-clinical 77 Phase I 89 Phase II 33 Phase III 67 Commercial Total number of companies - stakeholders in the cell therapy sector ~ 700. This includes ~250 therapeutic companies with ~340 cell-based therapeutic products (Lee Buckler, Cell Therapy Group, 2009) Cell product is defined as any cell-based product involving live cells ‘produced’ ex vivo intended for therapy
31. Cost/ profitability of approved cell products in US: Only about 2.2% of the overall cell therapy market is spent on manufacturing http://celltherapyblog.blogspot.com/2008/08/cell-therapy-manufacturing-market.html ~ 12% of cell therapy product manufacturing is currently outsourced to private, industry contract manufacturers product brand FDA approval donor profitability cost-effectiveness price, USD Carticel Genzyme 1997 autologous yes yes 17,000- 38,000 Apligraf Organogenesis 1998 allogeneic yes yes ~1,200 per use Provenge Dendreon 2010 autologous ? ? 93,000 (31,000 x3)
32. Allogeneic versus Autologous Manufacturing Summary Master Cell Bank Lot Tested Working Cell Banks Lot Tested Patient Doses Lot Tested Cell Expansion Cell Expansion or Purification Testing Patient or Donor Cell Ampoule or Dose Submitted for Testing Allogeneic / Universal Donor Autologous / Patient Specific courtesy of Jon Rowley , LO nza
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Editor's Notes
At a registry size of 10 million [bone marrow] donors, approximately 7 million additional donors are needed to increase the chance of matching by only 1% http://www3.interscience.wiley.com/journal/122614197/abstract The study showed that 50,000 donors would be required to provide at least one donor for 98% of the patients with at least a 4 out of 6 HLA match, to 80% with a 5 out of 6 match, and to 34% with a 6 out of 6 match http://www.haematologica.org/cgi/content/full/94/4/536
Allogeneic use of cord blood among children can be predicted based on the actual transplant rates. The cumulative probability is 1 in 5000 Autologous use of cord blood among children can be estimated based on the prevalence (ie: cumulative probability) of those indications for which clinical trials use autologous of CB We compare the autologous and allogeneic use of cord blood by plotting the cumulative number of cord blood treatments versus time, for the autologous data from PGCB and the allogeneic data from the WMDA. Looking at 2008, the number of autologous treatments is about 100 times lower than the number of allogeneic treatments. However, the rise in the cumulative number of allogeneic cord blood use is linear over the last few years, whereas that number for autologous use is rising faster than exponential. Medical societies or individual physicians who issue opinions on cord blood storage that ignore the fast growing autologous use of cord blood for mainly regenerative medicine are not making evidence-based recommendations.
(GVH and host-mediated immune clearance)
598 CB transplants for non-hematopoietic use reported in Europe. None of them indicated CB as a source of stem cells (EBMT survey activity 2009)
After release, antigen-presenting dendritic cells migrate to lymphoid organs and activate specific anti-tumor clon of cytotoxic T-cells. Alginate scaffold with VEGF and endothelial progenitors. VEGF could attract endogenous endothelial cells or support scaffold-embed ones and stimulate local neovascularization.
It is therefore highly interesting to note a comment from Geoff MacKay, CEO and President of Organogenesis that, “In the USA, on average, once every 2 minutes Monday to Friday a patient is treated with Apligraf.”
