SCID mouse reprogramming platform

SCID mouse differentiation and maturation platform: A unique solution to solve the issue of human cell-based assays in providing real translational solutions to industrial and researchers

The lack of cell maturity (clinical predictability) and necessary population homogeneity (reproducibility) are two major bottlenecks which currently prevent large-scale adoption of human cell-based assays. Univercell-Biosolutions has developed a unique and proprietary multistep process for the generation of large quantity of mature and pure population of human differentiated cells. This has been successfully tested for generating our human pancreatic β-cell line: EndoC-βH1 and is ongoing on several other cell types.

Univercell-Biosolutions SCID mouse differentiation and mataration platform is composed by two unique elements:

1- A “Maturation Bioreactor”: use of a SCID mouse  as a “bioreactor” for immature cell fate maturation,

2- A cell selection and amplification technology: introduction of an oncogene (SV40LT) under the control of a late stage specific promoter of the desired cell type providing a selective advantage and leading to a 100% pure and homogeneous unlimited population of relevant cells.

Thus combining this unique technology with the UB patented hiPSc cells differentiation protocols has also demonstrated potential to maturate to the adult final stage several cell types in providing several other cell type over the beta cells (neurons, cardiomyocytes…). Univercell-Biosolutions proposes the SCID mouse as differentiation and maturation bioreactor in partnership for developing new innovative human cell models.

This world unique proprietary solution has been successfully demonstrated on β cells leading to impressive results on the production of the first ever functional human pancreatic β cell line (EndoC- βH1) with similar skills to adult human β cell.

Next Strategic steps: How providing a human cell similar to the native human adult differentiated cells

Despite the success from EndoC- βH1, it is important to note that the insulin content of these cells has to be improved. One major source of difference comes from the fact that adult human β-cells are quiescent in vivo whereas EndoC-βH1 proliferates continuously. In this context, UB hypothesized that the function of the cell line could be drastically improved by excision (after expansion) of the SV40LT transgene (immortalization gene) which is responsible for continuous cell proliferation.

Fig1: Development of successive EndoC-βH cells versions aiming at defining the best strategy to obtain a human β cell fully similar to the native in vivo β cell.