He ended his talk by citing the reasons why he thinks rapamycin can be used to delay aging-related disorders such as OA, and why rapamycin is so beneficial to promoting articular cartilage repair, including its effect on angiogenesis (decreasing vascular endothelial growth factor [VEGF]), hypertrophic chondrocytes (decreasing collagen type 10A1 and MMP-13 expression), decreasing mTOR expression, and increased autophagy.
Clinical Application
Christian Jorgensen, MD, PhD, director of IRMB, Institute for Regenerative Medicine & Biotherapy, Montpellier, France, discussed some of the data now emerging from clinical trials on the therapeutic application of MDSCs in arthritis and osteoarthritis, and issues that still need to be addressed in making this potential therapy more feasible.
After reviewing some of the preclinical data showing the benefit of MDSCs in mouse studies, he emphasized that transferring these results to humans “is a different feat. It is easy to treat mice,” he said, but continued that treating humans with cells requires a team approach to address the myriad issues of using a therapy (cell) that may change behavior once injected in a body. He emphasized the need for a team approach when conducting human clinical trials in stem cell therapy, one that includes working closely with regulatory agencies, pharmacists dedicated to quality controls, as well as ethics committees.
He walked participants through a phase I study in which he and his colleagues assessed the safety of injecting autologous adipose-derived stromal cells (ASCs) to treat severe knee osteoarthritis in 18 patients. Designed as a dose escalation safety study, the trial included three cohorts of patients (50 patients in each) treated with low dose (2×106 cells), medium dose (10×106 cells) and high dose (50×106 cells).2 Results of the study showed that most of the patients in the low-dose group are doing well, said Dr. Jorgensen, and that those in the high-dose group have up to one year of clinical efficacy. He also said that some patients had no response to treatment, whereas the patients with the highest disease activity had the best results.
Based on the finding that the step cell therapy was safe, Dr. Jorgensen and colleagues are currently conducting an ongoing phase II study that will include 150 patients with severe knee osteoarthritis treated with autologous stem cells over the next year.
Although Dr. Jorgensen and colleagues are using autologous stem cells in their study, Dr. Jorgensen pointed out that more studies are now using allogenic stem cells given their reduced production costs and studies showing very similar responses in terms of safety and efficacy to autologous stem cells.
