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How Regenerative Medicine Is Changing the Future of Personalized Therapy GROWING THE DISTANCE How regenerative medicine is changing the future of personalized therapy. WRITTEN BY JEANNE BERKOWITZ, PH D MAGINE HAVING SKIN SO FRAGILE that even also developing applications to ameliorate pressure from the seams in a piece of clothing the debilitating eff ects of inherited genetic could cause painful blistering and injury. For diseases like epidermolysis bullosa. children with epidermolysis bullosa, a rare IPS cells represent a relatively recent advance genetic disease that can be caused by a single in the field of stem cell research. By artificially point mutation in a structural protein of the inducing expression of a handful of specific skin, this scenario is a painful daily reality. An genes in adult somatic cells, these cells can ongoing clinical research program in Colorado be reprogrammed to revert to an immature, holds promise to provide relief to these highly undiff erentiated, genetically rejuve- patients, and highlights the intense activity nated state with properties similar to those currently ongoing in Colorado in the field of of embryonic stem cells (ESCs). Like ESCs, regenerative medicine. iPS cells can be propagated and expanded Ganna (Anya) Bilousova, PhD, an assistant indefinitely in vitro and, in theory, be induced professor in the Department of Dermatology to diff erentiate into any cell type in the body at the Charles C. Gates Center for Regenerative with the goal of growing replacement tissues Medicine at the University of Colorado or organs to treat diseases or the degenerative Anschutz Medical Campus, heads a research eff ects of aging. program that aims to harness the regenerative “We can take cells from a patient as old as 80 power of induced Pluripotent Stem (iPS) cells years of age, induce those cells to become iPS for renewal and replacement of aging tissues cells, and they seem to revert to a rejuvenated and organs. Together with Dennis Roop, PhD, phenotype,” Bilousova says. “In theory, we can a professor and director of the Gates Center, potentially use these cells to grow entire, new, and with the assistance of colleague Igor young organs, with improved functionality, Kogut, PhD, an instructor in the Department that are specific to the patient the iPS cells of Dermatology, Bilousova’s laboratory is came from.” 20 BIOSCIENCECOLORADO 2016-2017 Colorado State University Clinical Sciences professor David Frisbie with a horse at the Equine Orthopaedic Research Center. GROWING THE DISTANCE 2016-2017 BIOSCIENCECOLORADO 21 AlloSource employee working in the tissue processing area. iPS cell genomes to safely correct faulty genes in order to treat epidermolysis bullosa as proof of concept for other genetic disorders. “We want to make genetic corrections,” Kogut says, “but that has to be achieved at the genome level, without introducing any additional nucleotide changes, and without leaving behind any kind of selection marker.” Kogut is therefore working with two diff erent cutting-edge genome editing techniques: TALEN (Transcription Activator-Like Eff ector Nucleases) and CRISPR/Cas9 (Clustered, Regu- larly Interspaced, Short Palindromic Repeats) to repair the disease-causing mutation, aft er which the cells will be diff erentiated and It’s not diff icult to see the potential of iPS diff erentiation to produce the desired cell grown into a skin substitute. Ultimately, the cells for use in regenerative medicine. Unlike types. Perhaps most fundamentally, Bilousova, goal is to develop these advances for com- ESCs, iPS cells are derived from adult somatic together with Korgut and Roop, is further im- mercialization, leveraging the considerable cells, and therefore do not involve the use of in proving so-called non-integrating approaches resources and expertise of the Gates Center. vitro fertilized embryos or ESC lines—sources to reprogramming somatic cells using mRNA, associated with significant societal, ethical, in order to avoid the risks of introducing new, legal, and scientific hurdles. They are also spe- permanent genetic mutations that could, in The partially demineralized cific to the patient being treated, presumably themselves, cause disease. allograft bone – the foundation for avoiding or reducing the possibility of immune “Our work is based on the fact that, fundamen- the AlloStem tissue [developed by rejection aft er transplantation. tally, proteins are the molecules that do the Bilousova’s research program is tackling some jobs within the cells, so that is what we need AlloSource] – provides a natural of the technical hurdles of translating the basic to express in order to reprogram the cells,” scaffold for new bone formation. science into the clinic. Her team is interested Bilousova says. The naturally occurring growth in identifying and developing optimal The ultimate goal is to adapt iPS cells for thera- tissue sources for somatic cells that will be peutic applications. Kogut’s research program is factors present in allograft induced to become iPS cells, and optimizing working to identify strategies for manipulating bone have been shown to promote new bone growth. With more than 85 faculty members at the Anschutz Campus and from other institutions all over Colorado, state-of-the-art core facili- ties, and an advanced cGMP biomanufacturing facility, the Gates Center represents a central hub for translational research in the field of regenerative medicine in Colorado. The center is not alone in its eff orts to harness the powers of this field. Academic and A National Resource forClinical Research commercial activities across the state indicate and that stem cell research and regenerative medicine will be a major focus for bioscience Your Partner in Personalized Medicine in Colorado in the decades to come. and Healthcare Innovation In Fort Collins, Colorado State University (CSU) recently received an anonymous $20 million donation to fulfill its $65 million fundraising goal to begin construction on the new CSU www.chiresearch.org Institute for Biologic Translational Therapies. 22 BIOSCIENCECOLORADO 2016-2017 The center was originally launched in late improved outcomes for patients compared 2014, with a $42.5 million gift – the largest to other commercially available stem cell cash gift in CSU history – from Denver-area transplant technologies. philanthropists John and Leslie Malone. Regenexx also conducts extensive research in The Malones became interested in stem stem cell therapies, including a procedure using cell research and regenerative medicine cultured mesenchymal stem cells in place of through their experiences with the Gail freshly isolated ones. While that procedure is Holmes Orthopaedic Research Center at not currently available as an approved therapy CSU, which helped them treat lameness in in the US, Regenexx has conducted clinical one of their world-class dressage horses studies for the procedure and continues to through arthroscopic surgery and the use investigate its potential for further development. of stem cell injections. Aft er endowing a BRING IN chair in Equine Sports Medicine at CSU, The healthy and expanding they decided to broaden their focus. They recognized that research and advances in ecosystem of academic and THE BEST. veterinary regenerative therapies, including commercial activity in this stem cells, gene therapies, replacement field suggests that our state tissues and organs, and novel proteins, would have extraordinary value, not only will be well positioned to With TriNet Life Sciences, for animals and their owners, but also for address this growth. you can offer the kind of rich treating human disease, degenerative disor- ders and aging. The new institute will serve The non-profit organization AlloSource, located benefit packages that help as a nucleus for that kind of translational in Centennial, Colo., is another key player in approach, in which discoveries in basic and you compete for the best regenerative medicine in Colorado. Founded pre-clinical research can develop in parallel in 1994, AlloSource develops, processes and talent out there. Our HR for both veterinary and clinical applications. distributes donated human tissue for use bundle also offers: The commercial potential of veterinary as allografts in medical procedures such as stem cell research at the Holmes Orthopae- knee replacement, joint repair, bone grafting, • Payroll dic Research Center has been demonstrat- spinal fusions and skin grafts for wound and ed by the spin-out of a commercial entity, burn care. Its tissue bank includes more than • Benefits ART (Advanced Regenerative Therapies, Fort 200 kinds of bone, cartilage, skin, soft-tissue • Risk & Compliance Collins). ART was co-founded in 2007, by and custom-machined allografts for use in Dr. David Frisbie, PhD, and Dr. John Kisiday, an array of life-saving and life-enhancing • HR Team PhD, both of whom are associate professors medical procedures. at the center. The company’s services focus Its most recent innovation, AlloStem, is partial- • Cloud Platform on providing autologous bone marrow stem ly demineralized allograft bone combined with cell collection, expansion and banking to adipose-derived mesenchymal stem cells. The treat equine and canine musculoskeletal partially demineralized allograft bone – the injuries and disorders. foundation for the AlloStem tissue – provides Another Colorado company, Regenexx, a natural scaff old for new bone formation. The located in Broomfield, Colo., also off ers au- naturally occurring growth factors present in Visit TriNet.com or call tologous bone marrow stem cell
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