Human induced pluripotent stem cell-derived planar neural organoids assembled on synthetic hydrogels.

Autor: Majumder J; Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA., Torr EE; Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA., Aisenbrey EA; Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA., Lebakken CS; Stem Pharm, Incorporated, Madison, WI, USA., Favreau PF; Stem Pharm, Incorporated, Madison, WI, USA., Richards WD; Stem Pharm, Incorporated, Madison, WI, USA., Yin Y; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA., Chang Q; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.; Departments of Medical Genetics and Neurology, University of Wisconsin-Madison, Madison, WI, USA., Murphy WL; Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA.; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Jazyk: angličtina
Zdroj: Journal of tissue engineering [J Tissue Eng] 2024 Feb 14; Vol. 15, pp. 20417314241230633. Date of Electronic Publication: 2024 Feb 14 (Print Publication: 2024).
DOI: 10.1177/20417314241230633
Abstrakt: The tailorable properties of synthetic polyethylene glycol (PEG) hydrogels make them an attractive substrate for human organoid assembly. Here, we formed human neural organoids from iPSC-derived progenitor cells in two distinct formats: (i) cells seeded on a Matrigel surface; and (ii) cells seeded on a synthetic PEG hydrogel surface. Tissue assembly on synthetic PEG hydrogels resulted in three dimensional (3D) planar neural organoids with greater neuronal diversity, greater expression of neurovascular and neuroinflammatory genes, and reduced variability when compared with tissues assembled upon Matrigel. Further, our 3D human tissue assembly approach occurred in an open cell culture format and created a tissue that was sufficiently translucent to allow for continuous imaging. Planar neural organoids formed on PEG hydrogels also showed higher expression of neural, vascular, and neuroinflammatory genes when compared to traditional brain organoids grown in Matrigel suspensions. Further, planar neural organoids contained functional microglia that responded to pro-inflammatory stimuli, and were responsive to anti-inflammatory drugs. These results demonstrate that the PEG hydrogel neural organoids can be used as a physiologically relevant in vitro model of neuro-inflammation.
Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.L.M. and C.S.L. are co-founders and shareholders in Stem Pharm, Inc., which is focused on commercial applications of neural organoids. C.S.L., P.F.F., and W.D.R. are employees of Stem Pharm, Inc.
(© The Author(s) 2024.)
Databáze: MEDLINE
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