The loss of substance induced by a cutaneous wound implies the creation of an artificial replacement tissue, composed of several specialized cell types. During the development of such a product, part of the work involves technology transfer of cell bank productions and quality control methods. This technology transfer enables the techniques, technologies and knowledge developed in our laboratory to be formally exported to an industrial partner.

The first objective of our project was to develop processes for differentiating human induced Pluripotent Stem Cells (hiPSC) into different cell types of interest, for example fibroblasts that belong in the dermic part of our product.

To validate the effectiveness of this differentiation process, we set up a battery of quality controls. The identity of our hiPSC-fibroblasts is validated by measuring the expression of certain markers using flow cytometry (CD90, CD73, Vimentin and TRA1- 81). To confirm their functionality, collagen and VEGF secretion are analyzed by ELISA assays, and collagen deposition is observed by immunofluorescence. Finally, a doubling time method is performed to validate the proper proliferation of our cells.

Once validated in the laboratory, each of these methods was the subject of a technology transfer to our industrial partner, enabling us to switch our processes to pharmaceutical-grade production. Firstly, the reproducibility and relevance of our results were assessed. Subsequently, steps were taken to “show” then “do together” then “do in parallel” these methods, to ensure that both partners would carry everything out exactly the same way.

The production of several cell batches has also enabled us to define specifications to validate whether a cell batch is compliant. This entire transfer process is supported by dedicated documentation (Standard Operating Procedure, Quality Control plan, transfer protocol and transfer master plan) to ensure that our processes are monitored and traceable.

In conclusion, the technological transfer of our hiPSC-fibroblasts differentiation process and the cell-associated quality controls will enable their production to pharmaceutical grade by our industrial partner. Ultimately, we will have qualified cell banks for the clinical production of our skin tissue therapy product.