Advantage and Core Benefit

- iEPCs can be easily induced from iPS cells, expanded cultured, and cryopreserved, and frozen cells can be used as a source of differentiation.
- Allows development of versatile human BBB models by co-culturing with pericytes and astrocytes

Background and Technology

Brain capillary endothelial cells (BMECs), one of the constituent cells of the blood-brain barrier (BBB), inhibit nonspecific entry of substances into the brain parenchyma through strong intercellular adhesion and expression of efflux transporters. In drug discovery, evaluation of BBB permeability is important, and a simple human BBB screening model is desired. Currently, rodent in vivo models and immortalized human BMECs exist to predict BBB permeability of drugs, but they are not sufficient due to lack of barrier function and different gene expression patterns.
The inventors focused on the fact that BMECs are embryologically derived from vascular endothelial progenitor cells (EPCs) and optimized a method for inducing differentiation from iPS cell-derived vascular endothelial progenitor cells (iEPCs) into iBMELCs. Supplement, TGFβ inhibitor (A83-01), and Laminin511 fragment were added to iEPCs derived from iPS cells, and iBMELCs with enhanced barrier function were successfully induced.

Data

- Expression of each marker in iEPCs and iBMELCs induced by this method. iBMELCs showed higher expression levels of PECAM1 and CDH5 than iBMELCs induced by existing methods and the cell line hCMEC/D3 for BBB evaluation, which was like hBMECs.

Patents

JPB6856240、PCT/JP2020/ 5255、PCT/JP2022/20827
H.Aoki et. al. Pharmaceutics. 2022 Dec 2;14(12):2697. doi:10.3390/pharmaceutics14122697

Researcher

Dr. Tadahiro Hashita and Tamihide Matsunaga (Nagoya City University)

Expectations

We are looking for a technology licensee for the induction of vascular endothelial progenitor cells (iEPCs) and brain capillary endothelial-like cells (iBMELCs) to a company interested in developing BBB models and other drug discovery support tools, cellular products, and master cells for cellular medicine. In particular, we have established a human BBB in vitro model by co-culturing with pericytes and astrocytes and are looking forward to collaborating with cell product development companies that can supply brain capillary endothelial-like cells (iBMELCs) using this technology.
Project No: WL-03442