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J. Control. Release, Available online 8 June 2024 | https://doi.org/10.1016/j.jconrel.2024.06.011
Stepwise dual-release microparticles of BMP-4 and SCF in induced pluripotent stem cell spheroids enhance differentiation into hematopoietic stem cells
Alvin Bacero Bello a,b, Kevin Kent Vincent Canlas b, Deogil Kim a, Hansoo Park b, Soo-Hong Lee a
aDepartment of Biomedical Engineering, Dongguk University, Seoul 04620, Republic of Korea
bSchool of Integrative Engineering, Chung-Ang University, Seoul 06911, Republic of Korea
Corresponding authors : Hansoo Park, Soo-Hong Lee
Abstract
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.
논문정보
- Research article
- 2024년 06월 (BRIC 등록일 2024-06-10)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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