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There is evidence that the application of mesenchymal stromal cells (MSCs) counteracts osteoarthritis (OA) progression. However, the prospect of extracting and expanding these cells might be limited. The aim of this study was to investigate whether hyaluronic acid (HA) supplemented with MSC-recruiting chemokine C-C motif ligand 25 (CCL25) can influence the natural course of spontaneous OA in the guinea pig. CCL25 concentration in synovial fluid (SF) was quantified with enzyme-linked immunosorbent assay. Boyden chamber cell migration assay was used to test CCL25-mediated migration of guinea pig MSC. Forty-nine 11-month-old male guinea pigs were divided into seven groups. The main treatments consisted of five intra-articular injections of HA in pure form and in combination with three doses of CCL25 (63, 693, and 6,993 pg) given at a weekly interval. The severity of cartilage damage was assessed by using a modified Mankin score. The measured average physiological concentration of CCL25 in SF of animals is 85 ± 39 pg/ml. MSC showed a 3.2-fold increase in cell migration at 1,000 nM CCL25 in vitro demonstrating the biological migratory activity of CCL25 on these cells. In vivo, treatment with HA alone did not reduce OA progression. Similarly, OA scores were not found significantly reduced after treatment with 63 pg CCL25 + HA. However, when compared to pure HA, treatment with 693 pg CCL25 + HA and 6,993 pg CCL25 + HA significantly reduced the OA score from 10.1 to 7.4 (−28%) and 8.4 (−20%), respectively. These data suggest that intra-articular injections of HA supplemented with CCL25 attenuates OA.

Die Aktualität der Herausforderungen kommunaler Selbstverwaltung steht in deutlichem Gegensatz zur dogmatischen Entfaltung des Art. 28 Abs. 2 GG. Andreas Engels hat daher das Anliegen, mit Hilfe einer dogmatischen Rekonstruktion eine belastbare Basis zur Bewältigung der Herausforderungen kommunaler Selbstverwaltung zu scha en. Der entwickelte Neuansatz erhebt dabei erklärtermaßen nicht den Anspruch, alle Fragestellungen zu beantworten. Wohl aber sollen Unzulänglichkeiten beseitigt werden, die auf Schwächen der bisherigen dogmatischen Deutungsmuster zurückzuführen sind. Der Autor will zur Rationalisierung der Argumentationsprozesse und zu einer höheren Konsistenz der Bereichsdogmatik beitragen.