Dr Jochen Ringe, Charité - Universitätsmedizin Berlin; Dr Kristin Fröhlich, Charité - Universitätsmedizin Berlin; Prof. Michael Sittinger, Charité - Universitätsmedizin Berlin
The intra-articular injection of hyaluronic acid (HA) in patients with osteoarthritis is so far the most promising treatment as it has been shown to delay the degeneration of cartilage. In this regard, HA is a well-tolerated visco-supplementation of the synovial fluid for mild and moderate osteoarthrosis joints. Until now however, there is no treatment option which is both able to delay or stop degeneration and which has regenerative potential.
A novel approach for the treatment of osteoarthritis and other cartilage defects is to inject biodegradable chemokine-loaded microparticles (e.g. Polylactid-Co-Glycolid (PLGA)-based) in a suspension of HA into the joint cavity. The microparticles ensure that the chemokines are released in a controlled manner (not at once) over a defined period of time thereby establishing stable chemo-attracting gradients that are required for effective stem cell recruitment to the site of cartilage defect. In vitro results surprisingly show that the combined administration of HA and the chemokine CCL25 (thymus expressed chemokine) or CXCL12 (stromal cell-derived factor-1α) synergistically promote the migration of human stem- and/or progenitor cells. Animal experiments in an osteoarthritis disease model of guinea pigs have been started.
Available for licensing or co-development
In vitro, ongoing in vivo experiments
DE 102010062288.5 priority patent application (01.12.2010)
Granted EP patent: EP 2645998 „Verwendung von Zytokine-freisetzenden, biodegradierbaren Partikeln in Hyaluronsäure zu Behandlung von Knorpeldefekten, insbesondere von Osteoarthrose“ (application date: 30 November 2011; granted: 20 August 2014)
EP patent validated in: DE, GB, FR, IT, CH, AT
Granted US patent: US 9,539,297 “USE OF CYTOKINE-RELEASING, BIODEGRADABLE PARTICLES IN HYALURONIC ACID FOR THE TREATMENT OF CARTILAGE DEFECTS, IN PARTICULAR OF OSTEOARTHROSIS”
(application date: 30 November 2011; granted: 10 January 2017)
Trends Biotechnol. 2014 Sep;32(9):483-92
Toward in situ tissue engineering: chemokine-guided stem cell recruitment.
Andreas, Sittinger, Ringe.