Fully defined matrices for organoid culture

Project SummaryCompared to standard two dimensional methods, three dimensional cell culture presents an opportunity to more reliably replicate and model in vivo physiology under controlled laboratory conditions. Organoid culture in particular has been shown to replicate in vivo tissue development, differentiation, and disease physiology in many cases. Recent reports however indicate that current cell culture substrates, including Matrigel, collagen and other recombinant extracellular matrix components, trigger undesirable phenotypes for modeling normal tissue function using cultured organoids. Here, we propose a collaborative Phase I program to expand the utility of inSoma’s proprietary Partially Ordered Polymers (POPs) in three-dimensional organoid culture with Scott Magness, PhD of the University of North Carolina at Chapel Hill, a leading expert in modeling gastrointestinal tissues using three dimensional culture systems. Our proof-of-concept program is intended to optimize POP formulations for three-dimensional culture, evaluate their support of organoid viability and proliferation, and employ transcriptomics to determine if aberrant phenotypes are reduced compared to other matrices, such as Matrigel. Once we establish lead formulations of the POP material for organoid culture, a Phase II program would evaluate organoids from other tissue types, including neural, pancreatic and liver tissues as well as potential testing of POPs as a support matrix for in vivo tissue engineering approaches. Each of these product classes has unique markets in both academic research, pharmaceutical screening and tissue engineering. inSoma has a robust intellectual property estate on POP biomaterials and given the rapid growth of three-dimensional culture for modeling in vivo physiology, we anticipate the product to address a significant market in the life science tools sector with specific advantages over market leaders such as Matrigel.Project NarrativeThree-dimensional cell culture has become a powerful means of replicating in vivo physiology under controlled in vitro conditions. Substrates for three-dimensional culture, such as Matrigel, remain undefined and highly variable however, leading to a wide variation in cellular phenotypes. Partially ordered polymers (POPs) from inSoma function as a fully-defined three-dimensional culture matrix. This material is made from recombinant proteins, allowing for reliable and consistent manufacturing methods, and has been shown to support cellular viability in culture. Here we propose to evaluate this material for both organoid and stem cell culture, large markets which urgently require a new option for more defined cell culture conditions.