TY - JOUR
T1 - Stepwise dual-release microparticles of BMP-4 and SCF in induced pluripotent stem cell spheroids enhance differentiation into hematopoietic stem cells
AU - Bello, Alvin Bacero
AU - Canlas, Kevin Kent Vincent
AU - Kim, Deogil
AU - Park, Hansoo
AU - Lee, Soo Hong
N1 - Publisher Copyright:
© 2023
PY - 2024/7
Y1 - 2024/7
N2 - Recently, the formation of three-dimensional (3D) cell aggregates known as embryoid bodies (EBs) grown in media supplemented with HSC-specific morphogens has been utilized for the directed differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), into clinically relevant hematopoietic stem cells (HSCs). However, delivering growth factors and nutrients have become ineffective in inducing synchronous differentiation of cells due to their 3D conformation. Moreover, irregularly sized EBs often lead to the formation of necrotic cores in larger EBs, impairing differentiation. Here, we developed two gelatin microparticles (GelMPs) with different release patterns and two HSC-related growth factors conjugated to them. Slow and fast releasing GelMPs were conjugated with bone morphogenic factor-4 (BMP-4) and stem cell factor (SCF), respectively. The sequential presentation of BMP-4 and SCF in GelMPs resulted in efficient and effective hematopoietic differentiation, shown by the enhanced gene and protein expression of several mesoderm and HSC-related markers, and the increased concentration of released HSC-related cytokines. In the present study, we were able to generate CD34+, CD133+, and FLT3+ cells with similar cellular and molecular morphology as the naïve HSCs that can produce colony units of different blood cells, in vitro.
AB - Recently, the formation of three-dimensional (3D) cell aggregates known as embryoid bodies (EBs) grown in media supplemented with HSC-specific morphogens has been utilized for the directed differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), into clinically relevant hematopoietic stem cells (HSCs). However, delivering growth factors and nutrients have become ineffective in inducing synchronous differentiation of cells due to their 3D conformation. Moreover, irregularly sized EBs often lead to the formation of necrotic cores in larger EBs, impairing differentiation. Here, we developed two gelatin microparticles (GelMPs) with different release patterns and two HSC-related growth factors conjugated to them. Slow and fast releasing GelMPs were conjugated with bone morphogenic factor-4 (BMP-4) and stem cell factor (SCF), respectively. The sequential presentation of BMP-4 and SCF in GelMPs resulted in efficient and effective hematopoietic differentiation, shown by the enhanced gene and protein expression of several mesoderm and HSC-related markers, and the increased concentration of released HSC-related cytokines. In the present study, we were able to generate CD34+, CD133+, and FLT3+ cells with similar cellular and molecular morphology as the naïve HSCs that can produce colony units of different blood cells, in vitro.
KW - Biomaterials
KW - Composite spheroids
KW - Controlled release
KW - Differentiation
KW - Gelatin microparticles
KW - Hematopoiesis
KW - Pluripotent stem cells
UR - http://www.scopus.com/inward/record.url?scp=85195380380&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2024.06.011
DO - 10.1016/j.jconrel.2024.06.011
M3 - Article
C2 - 38844177
AN - SCOPUS:85195380380
SN - 0168-3659
VL - 371
SP - 386
EP - 405
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -