View the complete Missouri Regional Life Sciences Summit supplement from the Kansas City and St. Louis Business Journals. Click here to view.
Brief case presentations of academic-industry and national collaborative success stories and lessons learned from small business
Kevin Truman, dean, School of Computing and Engineering, University of Missouri-Kansas City
James E. Thompson, dean, College of Engineering, University of Missouri-Columbia
Gabor Forgacs, George H. Vineyard Professor of Biological Physics, University of Missouri-Columbia
Organ Printing: a novel tissue engineering paradigm: Engineering new tissues, ideally from the patient’s own body cells to prevent rejection by the immune system, is a rapidly growing field that rests on three pillars: cells, supporting structures (or scaffold) and stimulating biological environment. However the use of scaffolds has been associated with chronic inflammation and impaired tissue-remodeling and maturation. We introduce a novel automated rapid prototyping method (bioprinting) that allows engineering three-dimensional custom-shaped tissue and organ modules without the use of any scaffold, thus making the final construct fully biological, as well as structurally and functionally closer to native tissues. Conveniently prepared bio-ink units (multicellular spheroids or cylinders composed of single or several cell types) are delivered into the bio-paper (a hydrogel support material) by a special-purpose bio-printer. The delivery of the discrete bio-ink units is controlled by architectural software consistent with the geometry and composition of the desired organ module. Structure formation takes place by the post-printing fusion of the discrete units. We demonstrate the technology by detailing the construction of blood vessel substitutes. We also discuss undergoing translational and commercialization efforts with the help of our seed-stage company, Organovo, Inc., as well as the market opportunities afforded by the technology.
Randall S. Prather, curators' professor, animal sciences, University of Missouri-Columbia
Genetically Engineered Swine Models to Study Diseases like Cystic Fibrosis: Swine have become important in biomedical research as they are excellent models for a variety of diseases including cardiovascular disease, atherosclerosis, cutaneous pharmacology, wound repair, cancer, diabetes, ophthalmology, toxicology research, lipoprotein metabolism, pathobiology of intestinal transport, injury and repair, as well as being considered potential sources of organs for xenotransplantation. Cystic Fibrosis (CF) is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR protein is responsible for chloride ion transport. Disruption of the function in humans results in meconium ileus, focal biliary cirrhosis, pancreatic destruction, liver lesions, and lung disease. Unfortunately disruption of this gene in mice, while affecting chloride transport, does not result in any of the symptoms that humans develop. In collaboration with the University of Iowa we have created pigs with either a knockout of the CFTR gene or a mutated version that is similar to 70% of the people with CF (ΔF508). These pigs are born with meconium ileus, focal biliary cirrhosis, pancreatic destruction, liver lesions and they develop lung disease. Finally there is a model to invasively study the development of CF, to monitor disease progression, and to develop treatments and therapies without experimenting on children with CF.
Peter Sutovsky, associate professor, reproductive physiology, division of animal sciences, University of Missouri-Columbia
Commercialization of novel biomarkers of male fertility in humans and farm animals: Each year, US infertility clinics treat 135,000 couples who fail to conceive naturally. Up to 40% of these infertility cases can be attributed to male infertility stemming from poor sperm quality. An additional 20% of couples present at the clinic with idiopathic, unexplained infertility, some of which is in fact hidden, misdiagnosed male infertility. Due to a paucity of accurate diagnostic methods and efficient treatments, the success rate of assisted fertilization, measured by live births, stagnates around the disappointing 35% margin. Many parallels exist between human male infertility and male reproductive performance in farm animals, where the estimated losses from inferior reproductive performance amount to millions of dollars annually, according to USDA.
Increased use of artificial insemination (AI) and commercial embryo transfer in pork and cattle industries puts pressure on AI companies to abandon outdated techniques for the evaluation of male infertility. Similarly, progressive infertility clinicians increasingly emphasize more accurate diagnostics of an infertile couple. However, male fertility assessment through semen evaluation is still dependent upon a highly subjective, poorly informative light microscopic semen evaluation. Sperm cells of normal appearance that are scored as normal (i.e. fertile) under a light microscope, often harbor hidden defects observable only at molecular level. Other types of sperm defects, in turn, are caused by sample handling and thus not reflective of subject’s true fertility. The search is thus on for biomarkers that would allow clinicians and AI lab technicians to objectively score the percentage of truly defective sperm cells in a semen sample.
While daunting, this challenge represents a unique opportunity for a reproductive biologists interested in technology development and commercialization. Through discovery of “negative markers of male fertility”, i.e. protein biomarkers that are associated exclusively with the defective sperm cells we are able to objectively measure the content of abnormal sperm cells in any human or animal semen sample. Such measurement methods are being adapted for light microscopic semen evaluation and development of simple dipstick test kits for doctor’s office and chute side fertility testing, as well as for novel flow cytometric platforms allowing high throughput, automated, objective screening. In humans, the increased content of negative biomarkers in a semen sample coincides with reduced likelihood of achieving a pregnancy after assisted reproduction. In farm animals, pregnancy rates after AI correlate negatively with the abundance of these negative fertility biomarkers in boar and bull semen.
Following biomarker discovery and validation supported mainly by federal research grants, several biomarkers are being commercialized in our lab with support from private companies as well as with funds from federal SBIR program and from the Missouri Life Sciences Trusts Fund commercialization grant program. As the next step to technologies for male fertility evaluation, a nanoparticle based cell depletion technique is being adapted in our lab for the purification of the fertile sperm cells from human and animal semen samples, with the goal of increasing the pregnancy rates in human assisted fertilization and farm animal artificial insemination. Other efforts are focused on the development of contraceptive vaccines applicable to both human and animal health. An unexpected opportunity arose from University of Missouri organized research/commercialization showcase which led to our collaboration with a private company in Columbia, MO, specializing in forensic and paternity testing: A test kit based on one of our human sperm biomarkers is being adapted for the detection of sperm cells in forensic rape case evidence. High demand exists for this novel crime fighting tool in the field of crime scene investigation.
Altogether, our efforts illustrate how, given a nurturing environment and encouragement, opportunities arising from university-supported basic research can be translated into marketable technologies bringing together the fields of human and animal health.
Joseph S. Tash, professor, molecular and integrative physiology, director, Interdisciplinary Center for Male Contraceptive Research and Drug Development, University of Kansas Medical Center
The “Male Pill”: The learning curve from basic science to the drug development pipeline and the strength of interdisciplinary collaboration: Nearly five decades have elapsed since the development of the female contraceptive hormone pill. During this time numerous alternative female contraceptive methods have also gained acceptance, however “the pill” and other hormone-based female contraceptive methods remain the most widely used. There are many couples where the female cannot use existing methods. For the male, effective contraceptive methods are limited to condoms and vasectomy. NIH, WHO, and the National Academy of Science Institute of Medicine have all stressed the need to develop new non-hormonal contraceptive methods. In the US, 30% of men use these male methods, so there is already a significant acceptance of male alternatives for actively participating in family planning. My basic research in male reproductive biology has always focused on identifying regulators of sperm or testis function that could be employed to develop a male contraceptive. Achieving this goal was accelerated in 2001 when a multidisciplinary collaboration between a medicinal chemists and a reproductive biologists at KU-Lawrence and KUMC was funded under a NIH contract to ‘Design and Test Reversible Non-Hormonal Male Contraceptives (Dr. Gunda I. Georg, PI; Joseph S. Tash, Co-I). The success of this collaborative effort has led to a second NIH contract, and a new NIH-funded U54 center “Interdisciplinary Center for Male Contraceptive Research and Drug Development” (Joseph Tash, Director; Gunda Georg, Assoc. Director). The overall effort now includes multiple institutions and reproductive biologists, medicinal chemists, molecular biologists, x-ray crystallographers and structural biologists, as well as experts from pharma. The productivity of this effort has resulted in numerous leads at various stages of the drug discovery and development pipeline. In addition to non-hormonal male contraceptives, spin-off agents have been identified as potential single dose non-surgical alternatives to spay/neuter in cats, dogs, and other feral animals, and a treatment for polycystic kidney disease. Thanks to the support of University of Kansas Institute for Advancing Medical Innovation (IAMI), our lead agents are now in pre-clinical toxicology. In addition, a new collaboration with the Oregon National Primate Research Center has resulted in the first studies of our lead contraceptive agent in non-human primates, where safety and efficacy are being proven. Both of these later studies will be key to promoting the transition of the lead agents into negotiations with the FDA, the start of human clinical trials, and gain of interest for commercialization and implementation as a new alternative for family planning. An overview of the process with additional comments regarding what has been learned along the way will be presented.