This is Tobin Magle, Biomedical Sciences Research Support specialist at the Health Sciences Library. I’m starting another blog series called “Librarians in the Lab” where I and other health sciences librarians visit labs on campus. This interaction will help us understand the type of work being done on campus, and give us some face time researchers that we serve so that they know better what we do. If you would like us to visit your lab, please contact email@example.com!
Cancer stem cells evade immune detection. (Courtesy of Brad Kubick, BS and Dennis Roop, PhD): Live imaging of cancer stem cells (green) evading immune cells (red) in a genetically engineered mouse model of skin cancer. In this model, skin cancers initiate around hair follicles (blue). This model may reveal how cancer stem cells avoid immune detection and suggest new therapeutic strategies to reverse this proces
Last week, research librarian Lilian Hoffecker and I visited the Gates Biomanufacturing Facility (GBF) located in Biosciences Park Center on Montview that opened in April. This facility allows the production of both cell therapies and biologics and is the only one of this caliber in an 800-mile radius. There are 25 other academic facilities that follow Good Manufacturing Practices (GMP) in the United States, only 5 of which are comparable to the quality and functionality of GBF, making GBF both geographically and functionally unique.
Having this great resource on campus would not have been possible without the contributions of the late Charles C. Gates, a local engineer, entrepreneur, and stem cell visionary. Health problems late in his life inspired him to fund translational medicine.
Generating human red blood cells (Courtesy of Greg Bird, PhD, Brian Turner, PhD and Yosef Refaeli, PhD): A major technological breakthrough now allows the expansion of human blood stem cells in the laboratory. The expanded human blood stem cells can be differentiated into erythroid progenitor cells (large pink cells with a nucleus (purple)) which give rise to mature red blood cells (small red cells). This technology makes it feasible to generate an unlimited supply of pathogen free human blood.
A generous donation from his foundation allowed the creation of the Charles C. Gates Center for Regenerative Medicine. This center runs 3 core laboratories, including the GMP facility. In Gate’s entrepreneurial spirit, the center focuses on getting discoveries made on campus into hospitals and clinics, which requires the services that GBF provides. This facility meets FDA safety regulations for human use. The environment inside the processing labs contains 1000x less particulates in than regular air to make sure the products are safe to use in humans. Additionally, they have implemented robust quality management systems and standard operating procedures to assure the highest quality.
The Gates Biomanufacturing Facility addresses two very hot topics in biomedical research: translational research and personalized medicine. The research coming into GBF has already been tested in animal models, but needs to clear strict quality hurdles to be tested in humans. The ultraclean environment and strict reporting processes at GBF allows treatments that were successful in animal models to be translated to the clinic and scale up their production to allow them to run phase 1 clinical trials on both cell and protein products (biologics).
The developing mouse eye (Courtesy of Tatiana Eliseeva, BS and Joe Brzezinski, PhD): Retinal stem cells (green) produce photoreceptors (purple). Photoreceptors die in diseases like age-related macular degeneration. Photoreceptors derived from patient-specific induced Pluripotent Stem (iPS) cells could be used to treat macular degeneration.
The truly amazing feature of GBF’s services is the applications to personalized medicine due to its association with the Gates Center for Regenerative Medicine. Stem cell therapies have been controversial in the past because of the use of embryonic stem cells (ESCs) for ethical reasons. Recent advances in stem cell research have made it possible to reprogram adult skin cells to create ESC-like cells. This strategy is advantageous for two reasons: it removes the ethical constraints around using ESCs and also reduces the risk of the patient’s body rejecting the cells. The GBF allows researchers to make clean cells from patient biopsy samples that can be reintroduced as a treatment. This technology can be used to treat conditions as diverse as macular degeneration, epidermolytic hyperkeratosis, repairing damaged heart tissue, cancer immunotherapies, bone and cartilage regeneration, not to mention producing human blood in the lab.
The services available at GMF are available to campus researchers at cost, which is a major advantage to anyone doing translational research on this campus. This activity will be subsidized by for profit work done in collaboration with biotech startup
Generating skin stem cells (Courtesy of Anya Bilousova, PhD and Dennis Roop, PhD): Human induced Pluripotent Stem (iPS) cells (pink) can be differentiated into ectodermal cells (green) which subsequently differentiate into skin stem cells. Nuclei are stained blue. This approach is being used to develop novel therapeutic strategies for inherited skin blistering diseases where patient-specific iPS cells are generated, genetically corrected and differentiated into normal skin stem cells which are then returned to the same patient as an autograft.
companies. This arrangement is mutually beneficial because it promotes campus research and is significantly more affordable than investigators building their own facility or outsourcing the work. Finally, having this facility on campus is important for recruiting top academic faculty who are interested in translational science and personalized medicine.
We received a tour of the facility and were able to see the cell products and biologics development areas and the quality control facilities. One of the most visually striking aspects of the facility is the wall art depicting some of the cell therapies that will be in development soon at GBF, which are dispersed throughout this post. We’re looking forward to hearing about all of the great discoveries that come out of the GBF. In the mean time, enjoy the images.
Generating dopamine secreting neurons (Courtesy of Wenbo Zhou, PhD and Curt Freed, MD): Human induced Pluripotent Stem (iPS) cells can be differentiated into human neuronal cells (red nuclei), some of which are dopamine secreting neurons (green cells with yellow nuclei). Following implantation into a rat model of Parkinson’s disease these human cells survive long term. The green fibers are connections of the human dopamine neurons to the rat brain cells. This approach may eventually be used to treat patients with Parkinson’s disease.
Gates Biomanufacturing Facility •
12635 E Montview Blvd. Suite 380 •
Thomas Payne Ph.D, Director of Cell Therapiesfirstname.lastname@example.org -303.724.7779
Patrick Gaines, Business Development – email@example.com – 720.281.2100
Timothy Gardner, Business Development – firstname.lastname@example.org – 303.724.7049
Regenerating Bone (Courtesy of Karin Payne, PhD): Bone allografts (dark circles) can be revitalized (green staining) using mesenchymal stem cells derived from human induced Pluripotent Stem (iPS) cells. Revitalized bone allografts can be used to enhance bone fracture repair and improve spine fusion.
Detecting hair follicle stem cells (Courtesy of Stanca Birlea, MD and David Norris, MD): A cross-section through a human hair follicle revealing the location of multipotent stem cells (green) in a region called “the bulge” which is located just above the site of insertion of the arrector pili muscle (red). Multipotent stem cells renew hair follicles, sebaceous glands and the epidermis in response to injury. The bulge is also the location of melanocyte stem cells which can be mobilized to repigment the skin of patients who suffer from vitiligo.
Generating cardiomyocytes (heart muscle cells) (Courtesy of Kunhua Song, PhD): Fibroblasts (skin cells) were directly reprogrammed into cardiomyocytes which contain sarcomeres (red) and nuclei (blue). This approach may reveal novel therapeutic strategies for heart repair.
Preventing radiation-induced oral mucositis (Courtesy of Xiao-Jing Wang, MD, PhD): Topical delivery of the fusion protein, tat-Smad7 (green), to oral mucosal cells (red) in a mouse results in its efficient uptake into nuclei and prevention of radiation-induced oral mucositis (extensive oral ulcers). This approach represents a novel therapeutic strategy to treat and prevent oral mucositis which develops in 40-70% of cancer patients receiving chemo- or radiation- therapy.
Imaging neural stem cells in zebrafish (Courtesy of Bruce Appel, PhD): Neural stem cells (green) produce myelinating glia (red) in the brain of a living zebrafish. This model is being used to screen for new drugs that may stimulate neural stem cells to proliferate and produce new glia in degenerative diseases of the nervous system.
Generating humanized cancer models,XactMice (Courtesy of Jason Morton, PhD, Greg Bird, PhD, Yosef Refaeli, PhD and Antonio Jimeno, MD, PhD): Dr. Refaeli’s major technological breakthrough which allows the expansion of human blood stem cells now makes it feasible to generate mice with tumor tissue and blood stem cells from the same patient. This is an image of human tumor which was excised from a male patient and transplanted onto a mouse whose bone marrow was reconstituted with human blood stem cells from a female. Staining for X chromosomes (red) and Y chromosomes (green) confirms that the male tumors cells (red and green dots) are infiltrated with female cells (red dots only) which were derived from the human blood stem cells. This model will serve as a new platform to discover new drugs which are directed against the tumor stroma and reversing the tumor’s ability to evade immune detection.
Migrating neural crest cells in zebrafish (Courtesy of Kristin Artinger, PhD): An elongated neural crest cell (green) migrating past the notochord (upper dark circle) and somite (red). Nuclei are stained blue. Neural crest cells are multipotent stem cells, giving rise to diverse cell lineages including peripheral neurons, glia, pigment cells (melanocytes) and craniofacial cartilage which forms the face. Understanding how neural crest cells differentiate into these different cell lineages may provide insight into the repair and treatment of birth defects such as cleft-lip and other craniofacial syndromes, as well as migration of cancer cells in melanoma.