Engineering stem cell fate with biochemical and biomechanical properties of microcarriers

Abstract

Microcarriers have been widely used for various biotechnology applications because of their high scale-up potential, high reproducibility in regulating cellular behavior, and well-documented compliance with current Good Manufacturing Practices (cGMP). Recently, microcarriers have been emerging as a novel approach for stem cell expansion and differentiation, enabling potential scale-up of stem cell-derived products in large bioreactors. This review summarizes recent advances of using microcarriers in mesenchymal stem cell (MSC) and pluripotent stem cell (PSC) cultures. From the reported data, efficient expansion and differentiation of stem cells on microcarriers rely on their ability to modulate cell shape (i.e. round or spreading) and cell organization (i.e. aggregate size). Nonetheless, current screening of microcarriers remains empirical, and accurate understanding of how stem cells interact with microcarriers still remains unknown. This review suggests that accurate characterization of biochemical and biomechanical properties of microcarriers is required to fully exploit their potential in regulating stem cell fate decision. Due to the variety of microcarriers, such detailed analyses should lead to the rational design of application-specific microcarriers, enabling the exploitation of reproducible effects for large scale biomedical applications.

Neural differentiation from pluripotent stem cells: The role of natural and synthetic extracellular matrix

“…To better understand the in vivo development and the "niches", i.e., microenvironment, of neural tissue development [15] , three-dimensional (3-D) ECMs, both natural and synthetic, have been investigated for efficient neural differentiation of hPSCs. 3-D ECM scaffolds provide not only physical support for cell adhesion, but also the structural and biomechanical cues that can be transduced into biochemical signals, affecting cellular composition during neural differentiation [17,18] . By regulating biochemical composition, biomechanical properties, and physical structure of 3-D ECMs, neural differentiation of hPSCs can be effectively controlled.…”

In vitro organogenesis from pluripotent stem cells

“…17,18 The impact of PSC-derived ECMs on cellular differentiation may rely on ECM-bound growth factors such as fibroblast growth factor (FGF)-2, the biochemical composition of ECMs, and the biomechanical properties of ECMs. 19 Endogenous ECMs deposited on Matrigel have been found to support the propagation of hPSCs due to the retention of the paracrine and autocrine factors such as Gremlin and Cerberus, the antagonists of the bone morphogenetic protein (BMP) signaling. 20 However, the complex ECM microenvironment that can coax the tissue development from PSCs remains to be further elucidated.…”

Dendritic cells derived from pluripotent stem cells: Potential of large scale production

“…EBs in suspension bioreactors have more uniform size distribution, less agglomeration, and similar percentage of the differentiated hematopoietic cells compared to static culture. To provide cell adhesion surfaces, microcarriers have also been applied in hPSC expansion and differentiation due to the scale up potential in stirred bioreactors [28] . In this review article, we discuss the potential of hPSCs as the cell source to generate DCs [through the intermediate stage of hematopoietic stem cells (HSCs)] (Figure 1) and the current progress in DC differentiation from hPSCs.…”