Effect of expansion of human umbilical cord blood CD34+cells on neurotrophic and angiogenic factor expression and function

The use of CD34 + cell-based therapies has largely been focused on haematological conditions. However, there is increasing evidence that umbilical cord blood (UCB) CD34 + -derived cells have neuroregenerative properties. Due to low cell numbers of CD34 + cells present in UCB, expansion is required to produce sufficient cells for therapeutic purposes, especially in adults or when frequent applications are required. However, it is not known whether expansion of CD34 + cells has an impact on their function and neuroregenerative capacity. We addressed this knowledge gap in this study, via expansion of UCB-derived CD34 + cells using combinations of LDL, UM171 and SR-1 to yield large numbers of cells and then tested their functionality. CD34 + cells expanded for 14 days in media containing UM171 and SR-1 resulted in over 1000-fold expansion. The expanded cells showed an up-regulation of the neurotrophic factor genes BDNF, GDNF, NTF-3 and NTF-4, as well as the angiogenic factors VEGF and ANG. In vitro functionality testing showed that these expanded cells promoted angiogenesis and, in brain glial cells, promoted cell proliferation and reduced production of reactive oxygen species (ROS) during oxidative stress. Collectively, this study showed that our 14-day expansion protocol provided a robust expansion that could produce enough cells for therapeutic purposes. These expanded cells, when tested in in vitro, maintained functionality as demonstrated through promotion of cell proliferation, attenuation of ROS production caused by oxidative stress and promotion of angiogenesis.

Automated summary

CD34+ cell-based therapies have been mainly used for hematological conditions. However, recent evidence suggests that CD34+ cells derived from umbilical cord blood (UCB) have neuroregenerative properties. This study aimed to investigate the impact of CD34+ cell expansion on their function and neuroregenerative capacity. The researchers expanded UCB-derived CD34+ cells using different combinations of LDL, UM171, and SR-1 and found that 14-day expansion resulted in over 1000-fold increase in cell numbers. The expanded cells showed up-regulation of neurotrophic and angiogenic factors, and promoted angiogenesis and cell proliferation while reducing oxidative stress. These findings suggest that the 14-day expansion protocol can generate sufficient CD34+ cells for therapeutic purposes, while maintaining their functionality.