An early objective of adapting human cells to tissue culture back in the 1950's was to remake tissues and organ components after growing up an expanded population. But the cells would not comply, instead they just grew as monolayers on culture dishes. Later, some researchers suspended cells in a collagen matrix that was then solidified giving the appearance of a 3D culture. Even better, epithelial cells attach and layer onto collagen, giving the appearance of an additional stratified tissue layer. This became the standard model for NIH funded projects, even though this artificial layering of cells does not create functional tissue layers, although it 'looks' organized. The NIH allowed the companies and researchers to edit pictures of the tissue models to show only the two discrete layers while cutting off the bottom of their pictures showing that a few cells of both types settled to the bottom of the growth chambers, interacting more 'randomly'. It was here that the signals were produced giving evidence of tissue interactions, but this is never acknowledged. Note also, these protocols and the ingredients of most culture media, have been kept secret, even though they are listed as being used in thousands of publications and NIH grants. This created profitable businesses for Mattek and tissue culture supply companies, such as Gibco/Thermo Fisher, who sold their businesses to Swedish and English companies, which protects them from U.S. intellectual property claims.

     Another stage in 3D organ development has been when stem cells were found to form a 3D sphere of cells when contained in a droplet of medium, known as spheroids or organoids. The NIH funded research institutes and companies as they rushed to patent stem cell lines that expressed any markers typical of differentiated organs. This stimulated companies to invest in finding new stem cell lines. These companies have had difficulty in finding uses for their patented cells, especially because the FDA hasn't approved them in patients. There is a fundamental disconnect because the FDA has a deep-seated fear of therapies that insert living cells into patients, especially if not the patient's own cells (allogeneic instead of autologous). The FDA has defined their job as a policing role to make sure living allogeneic cells are never given to a patient. Yes, it can occur in clinical trials but there are no approved allogeneic cells used in available treatments. The FDA, and/or the NIH, could take an active role by providing allogeneic cell lines approved for patient therapies. They have the resources to analyze such pre-approved cell lines for any dangers, such as endogenous viruses, or even by the funding of these efforts. If they made these cells available to companies there would be a large economic benefit as these cells would be used in a variety of therapies, yet policing suits them better.

     A recent round of NIH funded experimentation is growing out of the organoid effort where experimentation on embryonic stem cells targeting signal transduction pathways, and cytokine triggers of differentiation, is helping to map out the steps in gestation of embryos that occurs over many months in culture. In contrast, HOF Therapeutics CAP technology can use primary cells and/or stem cells in various combinations and has discovered a multi-step process that uncovers the signaling pathways required to assemble cells into complex structures with correct micro-physiology with some connection to wound healing, as occurs over days - not months. Because our method works with many cell combinations, we do not need to use patented cells. The NIH funded consortium of beneficiaries of proprietary 3D cell layering, patented cell lines, have not fully disclosed their assets developed using public tax funds. Allowing companies to manufacture medium without disclosing the formulations has slowed down the entire field of tissue engineering by years, including our own research. The medium companies are the most profitable and are vying for control of the field by offering their own models, leveraging their nondisclosed formulas.

     Dr. Hoeffler made a pivotal contribution in year 2000 with his scientific paper entitled "Spontaneous Cell Sorting of Fibroblasts and Keratinocytes Creates an Organotypic Human Skin Equivalent", advancing the concept of triggering cells to migrate into correct position to recreate complex physiologies. He received a U.S. patent on the technology and founded the commercial operation Xgene. We experienced major blowback in the U.S., while labs in Holland and now England have worked successfully with similar systems. Our CAP method has broader applications and has many advantages over these other systems. Some companies rely on the dominant funded paradigm believing their in-house efforts to find the combination of 'special stem cells' and proprietary commercial media will enable their 3D organ efforts, or even result in successful stem cell clinical trials. Work with HOF Therapeutics instead! We can advance your programs the most at a reasonable price and under terms where you retain your property rights.