Hudson Institute for Medical Research
Translational Challenges in Regenerative Medicine
1Translational Division, Hudson Institute for Medical Research, Melbourne, Australia
The Translating stem cell discoveries takes a strong motivation for academic researchers and considerable financial resources from both non-profit and for-profit sectors. In many respects it is best achieved by merging academic-medical researchers with focused and experienced industry resources. This model enables soundly based scientific discoveries to transit from the lab to the clinic with deep enough research resources and infrastructure to address unexpected barriers. Frequently, the mode of action of cell products remain obscured because the cells disappear rapidly even though some evidence for their therapeutic benefit can be registered in pre- and clinical trials. However, it is important to understand the mechanism of action of any cell product. This may be obscured by a lack of understanding the actual pathways causing disease perturbation and is also commonly one of limiting factors in cell-based therapies. Immune tolerance of allogeneic cell transplants remains a serious roadblock for regenerative medicine. Cell therapies aimed at long-term repopulation of damaged or diseased tissues, requires knowledge of the appropriate cell type and maturity needed for therapy (progenitor or mature end-differentiated cell). As are animal models that poorly or only approximately represent the scope of human disease. Age of the human population is not often accounted for in experimental studies but regenerative properties of tissues vary dramatically with age(1).
The success of chimeric antigen receptor technology for the destruction of cancer is an interesting model for cell therapies evolving rapidly after an extended period of basic research and preclinical testing (25 years) to ensure the validity and efficacy of clinical benefit (2).
The California Institute for Regenerative Medicine (CIRM) has been managing the translation in a unique way for a granting body using in-house scientists experienced with the preclinical and clinical trial pathways, development of milestones and go, no-go decisions. The teams also present to and meet with (12 monthly) an external panel of experts in the disease, cell manufacturing, regulatory requirements, clinical delivery, business and venture capital. The report is used to modify the approach by he team, or to terminate or redirect the team to an earlier stage. The process increases the success of progression preclinical studies to registered clinical trials (3).
1. Dimmeler S, Ding S, Rando TA, Trounson A. (2014) Translational strategies and challenges in regenerative medicine. Nature Medicine. 20(8):814-21.
2. Brower V. (2015) http://www.the-scientist.com//?articles.view/articleNo/42462/title/The-CAR-T-Cell-Race/
3. Trounson A. (2012) California institute for regenerative medicine: accelerating stem cell therapies in California and beyond. Stem Cells. 30(3): 357-9.