Firms will combine CompoZr and CombiCult platforms to develop ESC and iPSC protocols.

Plasticell and Sigma-Aldrich are partnering to develop new products for enabling and tracking the differentiation of stem cell lines. The collaboration will involve the use of Sigma-Aldrich’s CompoZr® zinc finger nuclease technology for engineering human stem cell lines via the targeted knock-in of fluorescent reporters. Plasticell will then use the cell lines in its CombiCult™ HTS system to develop novel stem cell differentiation protocols.

The resulting stem cells and media will be commercialized together in kits, and the reporter cell lines will in addition be linked to specific CombiCult screens for use in the optimized differentiation of human embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs). Under the terms of the deal, Plasticell will retain ownership of protocols for the directed differentiation of stem cells, and Sigma-Aldrich will market the reporter stem cell lines.

“We have already demonstrated that using fluorescent reporter lines in CombiCult experiments offers a highly convenient, real-time visual readout for stem cell differentiation,” states Marina Tarunina, Ph.D., Plasticell senior scientist. “Providing reporter cells as part of CombiCult enables us to offer industry partners a complete ‘turnkey’ solution of HTS with stem cells, ideally suited for in-house screening of compound libraries within pharmaceutical companies.”

“Efficient, directed differentiation of stem cells to predetermined cell lineages remains a major challenge in the field of ESCs and iPSCs,” adds Carl Schrott, director of marketing for stem cell research products at Sigma-Aldrich. “We are pleased to partner with stem cell differentiation expert Plasticell to develop complementary products that address this rapidly growing market segment.”

Sigma-Aldrich’s CompoZr technology has been developed to allow the creation of modified cell lines with targeted gene deletions, gene insertions, or gene corrections. The firm claims the technology generates targeted genetic alterations that are permanent and heritable, allows the creation of knock-out or knock-in cell lines in as little as two months, and requires no antibiotic selection for screening.

Plasticell’s Combicult platform is a multiplexing technology the firm claims enables millions of combinations of cell culture variables to be tested in parallel for identifying the optimal protocol for any given outcome in cell biology.

The miniaturized system involves growing colonies of cells on the surface of microscopic bead-based microcarriers, which are then shuffled through various combinations of growth media that vary in composition with respect to nutrients, growth factors, hormones, and synthetic chemicals. A key step in the procedure is the labelling of microcarriers with unique tags each time they are exposed to a different culture medium, so the movement of a cell unit through the different media can be tracked, Plasticell notes.

The firm’s deal with Sigma-Aldrich follows just a couple of weeks after it reported on a collaboration agreement with UCB. Under terms of this deal UCB will provide drug compound libraries with known biological targets, which Plasticell will screen using CombiCult to identify new cell-signalling pathways involved in stem cell biology, including tissue regeneration. The ultimate aim is to discover compounds with potential applications in directing stem cell differentiation or for use in stem cell media.

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