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Glomerulus-on-a-Chip. Life Up

Ashammakhi, Nureddin MD, FRCSEd, PhD1; Elkhammas, Elmahdi A. MD2; Hasan, Anwarul PhD3

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doi: 10.1097/TP.0000000000001896
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Organ-on-chip is an emerging technology for drug testing, disease modelling, and organ function modeling. Despite development of nephron-on-chip1 and its components, such as proximal-tubule-on-chip,2 glomerulus-on-chip has not been realized mostly due to lack of functional podocytes. To achieve this, Musah et al3 obtained terminally differentiated podocytes from human induced pluripotent stem cells, through stem cell differentiation. Previously, podocytes were also generated in organoids obtained from amniotic fluid stem cells,4 obtained from renal progenitors from urine,5 from renal progenitors located in the Bowman's capsule,6 and from human iPSCs using efficient protocol.7 Myeloid cells with immunosuppressive features were recently developed from iPSCs to accompany iPSC-derived allografts to prolong their survival.8 This may be integrated into the system in the future. Podocyte-like cells developed extensions and tight contacts resembling normal podocytes. In a microfluidic system, podocytes were cultured on one side of a laminin-coated membrane and endothelial cells on the other side (Figure 1). The system had also channels mimicking urine and blood flow. Production of basement-membrane collagen, tissue-tissue interface, and differential clearance of albumin and inulin were observed (99% of albumin was retained in the capillary side, whereas 5% of inulin was filtered to urinary side). In a renal injury model, podocyte disruption, loss of function, and death were seen. Neither podocyte cell-line conventional culture can mimic glomerular structure and function nor can animal studies always mimic human physiology. Alternatively, organ-on-a-chip can be precisely controlled and have high throughput. Although, authors argue that the system is not designed to engineer whole organ, it can be a part of multiorgan-on-chip or human-on-chip system to study multiorgan effect, secondary drug, and systemic toxicity. Ultimately, it may help replace animal testing, dialysis, or even organ function. By adding sensors and remote control, vast possibilities are open in the future for using data from point-of-care diagnostic microfluidic devices.9 Personalized medicine can be advanced using a person's own stem cells with patient involvement in planned care. Regenerative medicine may benefit by using 3D bioprinting of developed podocytes. Global organs-on-chips market projection is US $6.13 billion by 2025.10 Hence, the importance of this work is highlighted and greatly appreciated.

FIGURE 1
FIGURE 1:
Arrangement of glomerular organ-on-a-chip microfluidic device. Photograph (left two) and schematic illustration (right two) of the device having microchannels replicating glomerular urinary and capillary compartments separated by laminin-coated porous and flexible membrane on which cells were cultured. Cyclic mechanical strain was applied by stretching the membrane using vacuum. Reproduced with permission from Xinaris C, Benedetti V, Novelli R, et al. Functional human podocytes generated in organoids from amniotic fluid stem cells. J Am Soc Nephrol. 2016;27:1400–1411.4

REFERENCES

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