I saw you listed in your blog – Examples of the successful translation of methods to improve outcomes after clinical HSPC transplantation. Could you elaborate? What do you feel are the important culture conditions that translate to transplantation success?
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Hematopoietic Stem & Progenitor Cell Culture
Company: STEMCELL Technologies Inc.
Job Title: Principal Scientist
There have been several reports of clinical trials in which ex vivo expanded cord blood (CB) cells were transplanted together with a second non-manipulated CB unit. Typically the CD34+ cells are purified first and then expanded in a serum-free medium, such StemSpan™ SFEM, supplemented with cytokines and/or other agents.
Here are four examples of published studies in which clinical benefits were observed after CB expansion was used, and a short description of the method that was used in each:
- Delaney C et al. Nature Medicine 16: 232-236, 2010 –Cultured for 16 days with recombinant Notch-ligand and cytokines
- de Lima M et al. N Engl J Med. 367:2305-15, 2010 – Co-cultured for 14 days with mesenchymal stromal cells and cytokines
- Horwitz ME et al. J Clin Invest 124:3121-8, 2014 – Cultured for 21 days with nicotinamide and cytokines
- Cutler C et al. Blood 122: 3074-81, 2013 – Stimulated for 2 hours with Prostaglandin-E2
In all studies the accelerated engraftment of neutrophils (and in certain cases, platelets) was observed. The manipulated graft contributed to hematopoiesis during first weeks or months, but long-term hematopoiesis was mostly from the non-manipulated graft. It is thus possible that the culture methods only expanded short-term repopulating cells or improved their homing ability, but it is not clear if the most primitive cells with long-term repopulating ability were expanded or maintained in these cultures. Further improvements will likely come from studies examining the importance of graft composition on engraftment (e.g., the role of T lymphocytes in either promoting or inhibiting engraftment) and from the development better conditions to maintain or expand the most primitive HSCs in culture. Some of the new small molecule regulators of HSPC function, StemRegenin 1 (SR1) and UM171, are currently being tested for their potential to improve the engraftment potential of CB engraftment, but these studies are still at an early stage.