Improving the outcome of cord blood transplantation through cellular engineering
Dr. Pineault’s research is focused on the molecular and cellular mechanisms regulating the differentiation of hematopoietic stem cell (HSC). Through his applied research projects, he translates this knowledge to the development of new manufacturing processes and therapeutic strategies to benefit HSC transplantation practice.
Improving the reconstitution of the blood cells following a hematopoietic stem cell transplantation helps to speed up the recovery of patients, as well as reduce their dependency on transfusion products.
Hematopoietic stem cells (HSC) are essential to the continued healthy renewal of our blood cells. These same self-renewing properties mean HSC have great therapeutic potential. They are transplanted to patients to regenerate their hematopoietic (blood) system. They are also investigated for production of blood cells in culture. While HSC can be isolated from bone marrow, peripheral blood and umbilical cord blood, our laboratory is particularly focused on the latter. Umbilical cord blood contains a high concentration of HSC and provides a relatively accessible source of HSC for transplantation, especially when related HSC matched donors cannot be found. As Canadian Blood Services builds a national public cord blood bank, our laboratory’s expertise in cord blood derived hematopoietic stem cells is being leveraged to improve cord blood collection and manufacturing processes in order to improve the cord blood units that are being banked and ultimately used in patients.
In addition to supporting Canadian Blood Services operational activities, our laboratory is developing new strategies to improve transplantation outcomes. Using a cellular engineering approach, we aim to produce greater number of hematopoietic progenitor cells available for transplantation, to improve engraftment and to shorten the periods of cytopenia commonly associated with hematopoietic stem cell transplantation procedures. Expanded progenitors can be programmed to produce blood cells more rapidly through the optimization of culture conditions. Consistent with this, we have reported that cord blood progenitors expanded ex vivo have complementary and synergistic thrombopoietic and reconstitution potentials with non-expanded cord blood progenitors. Ongoing research aims include:
Improving the expansion of hematopoietic progenitors in culture
Improving the capacity of expanded hematopoietic progenitors to repopulate the marrow
Minimizing the costs and complexities associated with this cell therapy; and
Characterizing the immunological interplay between co-transplanted stem cell grafts.
Pineault N, Abu-Khader A: Advances in umbilical cord blood stem cell expansion and clinical translation. Exp. Hematol. 2015; 43:498-513.
Dumont N, Boyer L, Emond H, Saltik BC, Pasha R, Bazin R, Mantovani D, Roy D-C, Pineault N: Medium conditioned with MSC-derived osteoblasts improves the expansion and engraftment properties of cord blood progenitors. Exp Hematol 2014; doi:10.1016/j.exphem.2014.04.009
Émond H, Boyer L, Roy D-C, Pineault N: Co-transplantation of ex vivo expanded progenitors with non-expanded cord blood cells improves platelet recovery. Stem Cells Dev 2012; 21:3209-3219
Tounkara FK, Dumont N, Fournier S, Boyer L, Nadeau P, Pineault N: Mild Hyperthermia Promotes and Accelerates Development of Erythroid Cells. Stem Cells Dev 2012; 21:3197-3208
Çelebi B, Mantovani D, Pineault N: Irradiated mesenchymal stem cells improve the ex vivo expansion of hematopoietic progenitors by partly mimicking the bone marrow endosteal environment. J Immuno Methods 2011; 370:93-103.
Pineault N, Cortin V, Boyer L, Garnier A, Robert A, Therien C, Roy D-C: Individual and synergistic cytokine effects controlling the expansion of cord blood CD34+ cells and megakaryocyte progenitors in culture. Cytotherapy 2011; 11:467-480.