The regenerative medicine field is a hotbed of innovative research. The recent “Repairing the Body” conference, sponsored by Cranfield Health, showcased some of the cutting-edge work being done within industry and academia. The topics discussed ranged from immunological intervention to stem cell and other reparative therapies.
High-content screening is capable of embracing the biological complexities inherent in stem cell applications, according to Edward Ainscow, Ph.D., associate director of AstraZeneca’s advanced science and technology laboratory (ASTL).
Regenerative medicine is a focus area for the company’s new opportunities group, and ASTL’s high-content screening infrastructure is helping advance developments. AstraZeneca’s molecule libraries are now being screened for potential regenerative medicine applications in diabetic retinopathy, myocardial infarction, and osteoporosis using mesenchymal stem cells from adipose tissue, which can give rise to multiple cell types.
“We find these cells are a good workhorse and model tool for looking at how we can modify the differentiation pathways of stem cells,” said Dr. Ainscow. The researchers are using the HD IncuCyte™—a microscope in an incubator—to monitor differentiation in different media through studying changes in cellular morphology. This setup shows an increase in striated morphology as the stem cells differentiate into cardiomyocytes.
High-content screening also allows monitoring of the expression of differentiation markers. “High-content screening is well suited to regenerative medicine because it allows profiling of multiple events at the cellular and subcellular level,” added Dr. Ainscow. “Emerging developments in in vitro cellular systems will increase the opportunities in this area.”
The demand for total joint replacement from people under 65 suffering from osteoarthritis is likely to increase dramatically by 2030, explained Alan Getgood, M.D., clinical research associate at the University of Cambridge. Some of these “young people with old knees” develop traumatic osteoarthritis as a result of sport and recreational injuries to the cruciate anterior ligament and meniscal cartilages.
Dr. Getgood believes that these injuries could be addressed by using biological treatment at an early stage. Accordingly, he is working with the U.K. Technology Strategy Board and Orthomimetics (now part of the Belgian regenerative medicine company TiGenix) on Chondromimetic, a collagen scaffold that can be used to “plug” articular cartilage lesions, thereby helping regenerate articular cartilage by providing a structure for cells to attach and produce new tissue.
“This is potentially a fantastic biological carrier,” said Dr. Getgood. Current approaches to repair these injuries such as surgical microfracture and cellular therapy tend to produce a fibrous tissue that has a shorter life than natural hyaline cartilage, which has a more complex structure.
Dr. Getgood has been looking at how the addition of various biological factors such as mesenchymal stem cells from bone marrow, platelet-rich plasma, and recombinant growth factors to Chondromimetic might improve the regeneration of the articular tissue. Recombinant human fibroblast growth factor 18 (rhFGF18) (which Merck Serono licensed from Zymogenetics) looks particularly promising as it produces repair tissue that is more like hyaline cartilage.
Wound healing is an important application area in regenerative medicine. “We would like to find novel ways of healing disfiguring wounds arising from congenital conditions, accidents, and disease,” noted Enrique Amaya, Ph.D., The Healing Foundation professor of tissue regeneration at the University of Manchester.
“All organisms have quite remarkable wound-healing capacities that are present in the embryo but lost during adulthood.” To study how this capacity might be maintained during adulthood, Dr. Amaya is applying his long-time interest in using the embryo of the West African frog Xenopus tropicalis as a model organism.
Frog embryos have many advantages—all the organs can be visualized, allowing many events to be monitored; the embryos can be produced in large numbers; and they are accessible at all stages of their development. There are also many genetic similarities between frogs and humans—one of the main conclusions that was made following the recent sequencing of the X. tropicalis genome.
Embryos heal quickly and completely, with no scarring, while adult healing is slow, incomplete, and produces a scar. Using frog embryos, Dr. Amaya set out to discover if the difference arises because embryos do not mount an inflammatory response to injury, while adults do. He learned that embryos do, in fact, produce inflammatory cells on injury. “But we think these cells differ from those produced by adults.” As a result, they have been studying the marker proteins expressed by these cells.
In other research, Dr. Amaya’s team is looking at tissue regeneration in the tadpole where an injured tail will regenerate in a functional (if not perfect) fashion. Microarray studies show which genes are induced on injury and during the regeneration.