TY - JOUR
T1 - A Novel High-Throughput Screening Platform Reveals an Optimized Cytokine Formulation for Human Hematopoietic Progenitor Cell Expansion
AU - Tarunina, Marina
AU - Hernandez, Diana
AU - Kronsteiner-Dobramysl, Barbara
AU - Pratt, Philip
AU - Watson, Thomas
AU - Hua, Peng
AU - Gullo, Francesca
AU - Van Der Garde, Mark
AU - Zhang, Youyi
AU - Hook, Lilian
AU - Choo, Yen
AU - Watt, Suzanne M.
N1 - Publisher Copyright:
© Copyright 2016, Mary Ann Liebert, Inc. 2016.
PY - 2016/11/15
Y1 - 2016/11/15
N2 - The main limitations of hematopoietic cord blood (CB) transplantation, viz, low cell dosage and delayed reconstitution, can be overcome by ex vivo expansion. CB expansion under conventional culture causes rapid cell differentiation and depletion of hematopoietic stem and progenitor cells (HSPCs) responsible for engraftment. In this study, we use combinatorial cell culture technology (CombiCult®) to identify medium formulations that promote CD133+ CB HSPC proliferation while maintaining their phenotypic characteristics. We employed second-generation CombiCult screens that use electrospraying technology to encapsulate CB cells in alginate beads. Our results suggest that not only the combination but also the order of addition of individual components has a profound influence on expansion of specific HSPC populations. Top protocols identified by the CombiCult screen were used to culture human CD133+ CB HSPCs on nanofiber scaffolds and validate the expansion of the phenotypically defined CD34+CD38lo/-CD45RA-CD90+CD49f+ population of hematopoietic stem cells and their differentiation into defined progeny.
AB - The main limitations of hematopoietic cord blood (CB) transplantation, viz, low cell dosage and delayed reconstitution, can be overcome by ex vivo expansion. CB expansion under conventional culture causes rapid cell differentiation and depletion of hematopoietic stem and progenitor cells (HSPCs) responsible for engraftment. In this study, we use combinatorial cell culture technology (CombiCult®) to identify medium formulations that promote CD133+ CB HSPC proliferation while maintaining their phenotypic characteristics. We employed second-generation CombiCult screens that use electrospraying technology to encapsulate CB cells in alginate beads. Our results suggest that not only the combination but also the order of addition of individual components has a profound influence on expansion of specific HSPC populations. Top protocols identified by the CombiCult screen were used to culture human CD133+ CB HSPCs on nanofiber scaffolds and validate the expansion of the phenotypically defined CD34+CD38lo/-CD45RA-CD90+CD49f+ population of hematopoietic stem cells and their differentiation into defined progeny.
KW - Alginate encapsulation
KW - CombiCult
KW - Ex-vivo expansion
KW - Hematopoietic stem/progenitor cells
KW - High-Throughput-Screening
UR - http://www.scopus.com/inward/record.url?scp=84994633753&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994633753&partnerID=8YFLogxK
U2 - 10.1089/scd.2016.0216
DO - 10.1089/scd.2016.0216
M3 - Article
C2 - 27554619
AN - SCOPUS:84994633753
SN - 1547-3287
VL - 25
SP - 1709
EP - 1720
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 22
ER -