Shabari Tipnis1, Chandra Viswanathan1. 1. Regenerative Medicine, Reliance Life Sciences Pvt Ltd, Dhirubhai Ambani Life Sciences Centre, R-282, TTC area of MIDC, Thane Belapur road, Rabale, Navi Mumbai -400701, Maharashtra, India.
Abstract
BACKGROUND AND OBJECTIVES: The field of Umbilical cord blood (UCB) hematopoietic stem cell transplantation has had an amazing run since 1988. UCB is being increasing used in related and unrelated transplant settings. A major hurdle, however, in the use of UCB is its low cell dose, which is largely responsible for an elevated risk of graft failure and significantly delayed neutrophils and platelet engraftment. Strategies to increase CD34(+) HSC/HPC dose are under development as a direct correlation has been shown between these counts and time for engraftment. One strategy includes the ex vivo expansion of UCB derived CD34(+) cells. METHODS AND RESULTS: We show that the umbilical cord derived mesenchymal stem cells (UCMSCs) can be used as supporting cells for ex vivo expansion of CD34(+) cells using low concentrations of cytokine cocktail. The UCMSCs release the cytokines required for maintenance and proliferation of CD34(+) cells in the ex vivo culture conditions. More than 25 fold increase in total nucleated cell count (TNC) and more than 20 fold increase in CD34(+) cell count has been obtained using this co-culture system. CONCLUSIONS: UCMSCs from both, autologous and allogeneic origin can be used for expansion of UCB derived CD34(+) cells. The ease of availability and immunoprivileged nature of UCMSCs further holds promise in their use in an allogeneic transplant setting.
BACKGROUND AND OBJECTIVES: The field of Umbilical cord blood (UCB) hematopoietic stem cell transplantation has had an amazing run since 1988. UCB is being increasing used in related and unrelated transplant settings. A major hurdle, however, in the use of UCB is its low cell dose, which is largely responsible for an elevated risk of graft failure and significantly delayed neutrophils and platelet engraftment. Strategies to increase CD34(+) HSC/HPC dose are under development as a direct correlation has been shown between these counts and time for engraftment. One strategy includes the ex vivo expansion of UCB derived CD34(+) cells. METHODS AND RESULTS: We show that the umbilical cord derived mesenchymal stem cells (UCMSCs) can be used as supporting cells for ex vivo expansion of CD34(+) cells using low concentrations of cytokine cocktail. The UCMSCs release the cytokines required for maintenance and proliferation of CD34(+) cells in the ex vivo culture conditions. More than 25 fold increase in total nucleated cell count (TNC) and more than 20 fold increase in CD34(+) cell count has been obtained using this co-culture system. CONCLUSIONS: UCMSCs from both, autologous and allogeneic origin can be used for expansion of UCB derived CD34(+) cells. The ease of availability and immunoprivileged nature of UCMSCs further holds promise in their use in an allogeneic transplant setting.
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