research highlights STEM CELLS Inside a mouse brain, human cerebral organoids can show their potential. flurry of excitement has surrounded organoids as models of human A disease and development. The stem- cell-derived three-dimensional structures reconstitute many of the properties found in native tissue. But investigators are also acutely aware of their limitations. Rusty Gage at the Salk Institute and his group have found that a location in the mouse brain supports human organoid development and can overcome some constraints imposed by cell culture. Organoids tend to mimic young, developing tissues. Both their size and the A mouse brain section with GFP-expressing extent of their development are limited by Premium organoid cells 90 days after grafting (nuclei are the absence of blood vessels, which leads DAPI-stained). Reproduced with permission from labware for to cell death during prolonged culture. The Mansour et al. (2018), Springer Nature. Gage team, led by postdoc Abed Mansour, research and asked whether organoids would be healthier in the context of a living animal. discovery Long ago, Gage showed that it was fact limited only by the short life span of the possible to transplant human tissue to NOD SCID mouse hosts. Gage is looking to the superior colliculus of the rat brain. push the current limits of cell maturation by Cell and Tissue Culture “I remembered this methodology that exploring the use of longer-lived strains. The I developed and worked on in Sweden system can also be used to study immune • Three different color coded 35 years ago,” he says, and this prompted activity, a component that is missing in brain growth surfaces him to try organoid tissue. Where other and other organoid studies. The researchers • Optimized, user-friendly efforts at organoid transplantation failed, detected scavenging cells called microglia geometries Gage’s team found that 50-day-old cerebral in the graft, though Gage cautions that their organoids generated from GFP-expressing origins have not been confirmed. • Labeling of all products human embryonic stem cells could thrive in Transplanted organoids have the with LOT number and this location. potential to provide better disease modeling, expiration date The superior colliculus is a special but the approach is limited by the need environment that sits atop a rich bed of for surgery and organoids of high blood vessels. It takes a steady hand, but quality, and by the fact that each animal Sterile/ DNA-/ DNase-/ anyone can be trained to do the surgery. accommodates only a single organoid. RNase-/ Pyrogen-free/ non-cytotoxic The key, says Gage, is to “really clean it up The researchers are now examining the so there’s no bleeding at all and you haven’t analogous cavity in rat brains, which nicked the surfaces of the colliculus.” can accept four or five organoids and Transplanted organoids were healthy; thus potentially allow the study of cell they showed progressive differentiation interactions across organoids representing of neural and glial cell types, were devoid different brain regions. They have yet to find of cell death, accepted blood vessels and any evidence of modulated mouse behavior sent axonal projections into host tissue. but are proceeding with caution, given the FREE Organoids imaged through cranial windows high degree of functional integration. showed regular blood flow and calcium Tal Nawy spiking. Electrophysiology suggested the maturation of neural networks, and samples! Published online: 31 May 2018 inroducing an optogenetic construct enabled https://doi.org/10.1038/s41592-018-0029-8 the stimulation of electrical activity in grafted neurons by laser light, with effects Research papers www.sarstedt.com in host tissue. Mansour, A. A. et al. An in vivo model of functional Organoids remained healthy for up to and vascularized human brain organoids. firstname.lastname@example.org 283 days after transplantation, and were in Nat. Biotechnol. 36, 432–441 (2018). Nature Methods | VOL 15 | JUNE 2018 | 403–409 | www.nature.com/naturemethods © 2018 Nature America Inc., part of Springer Nature. All rights reserved.
Nature Methods – Springer Journals
Published: May 31, 2018
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