Perspektiven klinischer mesenchymaler Stammzelltherapie bei muskuloskeletalen Erkrankungen in Deutschland

Zusammenfassung

Studienziel: Die Behandlung großer Knochendefekte nach Tumorresektionen, bei Endoprothesenwechseloperationen oder in der Frakturversorgung stellt in der Chirurgie des Bewegungsapparats häufig ein Problem dar. Aufgrund der mit dem Einsatz von Knochentransplantaten und Knochenersatzstoffen verbundenen Probleme besteht ein Bedarf nach Versorgungsalternativen. Eine mögliche Option sind regenerative Therapieansätze mit mesenchymalen Stammzellen (MSC). Material und Methodik: Anlässlich eines Expertenworkshops der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie wurde die bisherige Datenlage zum Einsatz von MSC im experimentellen und klinischen Bereich zusammengefasst und das Potenzial zur künftigen Durchführung klinischer Studien geprüft. Ergebnisse: In-vitro-Untersuchungen und tierexperimentelle Studien zeigen positive Effekte von MSC bei der Behandlung von Knochendefekten. In der vorliegenden Arbeit werden die gesetzlichen Rahmenbedingungen skizziert, die zur Durchführung klinischer Prüfungen von MSC eingehalten werden müssen. Ferner werden wissenschaftliche und regulatorische Aspekte für eine erfolgreiche Antragstellung diskutiert. Schlussfolgerung: Es sind weitere klinische Studien erforderlich, um das tatsächliche Potenzial der Applikation mesenchymaler Stammzellen bei Erkrankungen und Verletzungen des Bewegungsapparats einschätzen zu können. Bei der Planung und Durchführung sind im Rahmen der geltenden gesetzlichen Vorgaben auch spezifische Anforderungen zu berücksichtigen (z. B. GMP-gerechte Fertigung, GLP-gerechte Tierstudien), die eine verstärkte Zusammenarbeit der Forschungszentren sinnvoll machen. Darüber hinaus sind frühzeitige Beratungen durch die regulatorischen Behörden empfehlenswert, um eine Zulassung als Voraussetzung für die Standardtherapie mit MSC zu erhalten.

Abstract

Aim: The treatment of large bone defects remains a challenge for the orthopaedic surgeon. Regenerative therapies with the use of mesenchymal stem cells (MSC) may provide an alternative to autogenous bone transplantation, callus distraction or the use of allografts. Material and Methods: On the occasion of an expert workshop of the German Society for Orthopaedic and Trauma Surgery, a literature search regarding studies with the use of MSC was performed to evaluate its potential for future clinical studies. Furthermore, the legislative requirements were examined. Results: Various in vitro and animal studies showed the benefit of MSC in bone regeneration. However, there are sparse data from clinical studies. Due to recent legislative changes there are several regulatory demands to meet if clinical studies are performed with MSC. Conclusions: For further evaluation of the role of MSC in the treatment of bone defects there is a need for clinical trials. The current paper provides some assistance for the successful application for clinical trials with MSC. Planning and performance of these studies may require early consultation with the regulatory authorities and cooperation of research centres in order to obtain authorisation for the evaluation of MSC. Preclinical data have to be obtained according to good laboratory practice with equivalent protocols that will be used in the clinical trials. In the latter the implementation of the guidelines for good clinical practice are mandatory.

Schlüsselwörter

Stammzellen - Knochendefekte - klinische Studien - Gesetzgebung - Therapie

Key words

stem cells - bone defects - clinical trial - legislation - therapy

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