Directing Human Induced Pluripotent Stem Cell-Derived Embryonic-like Organoid with 3D Biomimetic Cryogel Mechanical Microenvironment for Neural Induction.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20642
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Vadivelu Raja Kumar 国立研究開発法人理化学研究所, 開拓研究本部, 基礎科学特別研究員 (60963543)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: Cryogel / Mechanical Constraint / iPSCs / Axial convergence / Germ layers / Neural fate / Neuromesodermal

Outline of Final Research Achievements

This project introduces the application of a simple agarose-based cryogel that can trap iPSCs and confine them. Thus, compacted cells sense mechanical constraints and promote differentiation in a 3D growth phase without the use of specific morphogens. The aggregates showed features of embryonic development, which display Anterior/Posterior (A-P) axis development and the presence of three germ layers along the axial convergence. The detailed cell specification reveals the capacity to self-organize into a rudimentary neural fate along the A-P axis. Notably, the transition of core pluripotency protein Sox2+ cells to prime state pluripotency is marked by Otx2 which is in the state of the stable epiblast. Later, it contributes to promoting mutually exclusive patterns between Otx2 and T-Bra. Thus, these findings can provide new insight into iPScs/material interaction in promoting neuromesodermal fate in an embryonic context.

Free Research Field

Embryonic organoid

Academic Significance and Societal Importance of the Research Achievements

The projects provide a simple approach that highlights cell/material interface platform. This platform can generate embryonic organoid derived from iPSCs. Further, useful to scale up to an organoid-on-chip model for drug testing to prevent fetal toxicity and miscarriage.