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Micro-Engineered Models of Development Using Induced Pluripotent Stem Cells


Micro-Engineered Models of Development Using Induced Pluripotent Stem Cells

Pallavi Srivastava et al. Front Bioeng Biotechnol.


During fetal development, embryonic cells are coaxed through a series of lineage choices which lead to the formation of the three germ layers and subsequently to all the cell types that are required to form an adult human body. Landmark cell fate decisions leading to symmetry breaking, establishment of the primitive streak and first tri-lineage differentiation happen after implantation, and therefore have been attributed to be a function of the embryo's spatiotemporal 3D environment. These mechanical and geometric cues induce a cascade of signaling pathways leading to cell differentiation and orientation. Due to the physiological, ethical, and legal limitations of accessing an intact human embryo for functional studies, multiple in-vitro models have been developed to try and recapitulate the key milestones of mammalian embryogenesis using mouse embryos, or mouse and human embryonic stem cells. More recently, the development of induced pluripotent stem cells represents a cell source which is being explored to prepare a developmental model, owing to their genetic and functional similarities to embryonic stem cells. Here we review the use of micro-engineered cell culture materials as platforms to define the physical and geometric contributions during the cell fate defining process and to study the underlying pathways. This information has applications in various biomedical contexts including tissue engineering, stem cell therapy, and organoid cultures for disease modeling.

Keywords: biomaterials; development; gastrulation models; iPS cells; micropatterning; morphogenesis.


Figure 1
Figure 1
(A) Graphical representation of effects of biomechanics and geometry in coordinating cell organization and germ-layer differentiation during embryonic development. (B) Various biochemical and biomechanical factors which have been documented to induce stem cell (MSC and PSCs) differentiation patterns in-vitro. Combining two or more of these factors for documenting cumulative cell responses is useful for understanding ECM based tissue modeling approaches.
Figure 2
Figure 2
(A) ES cells spatially organize themselves into three germ layers following BMP4 induction, depending on the size of the circle, creating a 2D gastrulation model. Image reused with permission (Deglincerti et al., 2016b) Nat Protoc 2016. (B) A semi-3D model of post-implantation amniotic sac embryoid (PASE)—The closest human model recapitulating multiple post-implantation embryogenic events. Image reused with permission (Shao et al., 2017) Nat Communications, 2017.

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