TY - JOUR
T1 - Effect of expansion of human umbilical cord blood CD34 + cells on neurotrophic and angiogenic factor expression and function
AU - Watt, Ashalyn P.
AU - Kirkland, Mark
AU - Nekkanti, Lakshmi
AU - Pham, Yen
AU - McDonald, Courtney
AU - Malhotra, Atul
AU - Moeneclaey, Guy
AU - Miller, Suzanne L.
AU - Jenkin, Graham
N1 - Funding Information:
Open Access funding enabled and organized by CAUL and its Member Institutions. This work was supported by the Victorian Government’s Operational Infrastructure Support Program. AW is a recipient of a Science and Industry Endowment Fund STEM + Business Postdoctoral Fellowship, jointly funded by Cell Care Australia. This work is also supported by a Monash Health Foundation research grant.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - CD34
KW - Cell expansion
KW - Haematopoietic stem cells
KW - Neurotrophins
UR - http://www.scopus.com/inward/record.url?scp=85123993005&partnerID=8YFLogxK
U2 - 10.1007/s00441-022-03592-2
DO - 10.1007/s00441-022-03592-2
M3 - Article
C2 - 35106623
AN - SCOPUS:85123993005
SN - 0302-766X
VL - 38
SP - 117
EP - 132
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 1
ER -