Engineering stem cell niches in bioreactors

Figure 1 Important stem cell niche factors regulating stem cell proliferation and differentiation in bioreactors. The niche factors include regulatory factors (such as oxygen), extracellular matrix (synthetic and native), physical forces and paracrine/autocrine factors. ECM: Extracellular matrix.

Figure 2 In situ measurement of oxygen concentration during stem cell differentiation. A: Multi-well plate with an oxygen sensor in each well; B: The starting undifferentiated human embryonic stem cells (ESCs); C: The human ESC derived cardiomyocytes expressing cardiac marker NKX2.5 and cardiac troponin I (adapted from reference Xu et al[120]); D: The bioreactor system with a sensor platform for reading the oxygen tension during in situ differentiation.

Figure 3 Microbioreactor array for human pluripotent stem cells differentiation. A: Top view of the microbioreactor array assembly; B, C: Photographs of the assembled microfluidic platforms. A contrast dye was used in images (B) and (C) to show the fluid paths. Adapted from Cimetta et al[100].

Figure 4 Perfusion bioreactor array for cell-based assay. A: Schematic drawing of the device composed of top and bottom layers; B: Perspective view of the assembled device to form microscale channels and wells; C: Design of individual cell culture well and relay well formed by two layers, with cell culture well that can be filled with any modular tissue engineering scaffold such as PET fibrous matrix; D: Perspective drawing of the top and bottom frames for frame-assisted assembly; E: Photograph of device in assembly with each inlet connecting to a flexible connector capped to prevent contamination (highlighter window); F: Photograph of assembled device at work with each inlet connected to an external tubing through a flexible connector (highlighter window). Reproduced from reference Wen et al[14].