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Einsatz von mesenchymalen Knochenmarkstammzellen für die Ex-vivo-Knorpelregeneration

Use of bone marrow mesenchymal stem cells for ex vivo cartilage regeneration

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Zusammenfassung

Krankheiten und Verletzungen des artikulären Knorpels führen häufig zu lebenslangen chronischen Schmerzzuständen. Bei fokalen Knorpeltraumata ist die moderne Medizin auf kurzzeitige Schmerzentlastung und Entzündungskontrolle begrenzt. In extremen Fällen wird das betroffene Gewebe operativ entfernt und durch synthetische Prothesen mit begrenzter Lebensdauer ersetzt. Seit 1994 werden zusätzlich zellbasierte Therapien zur artikulären Knorpelregeneration eingesetzt. Diese therapeutischen Ansätze stellen eine gesunde Zellpopulation für den fokalen Defekt bereit und benötigen differenzierte Chondrozyten von einer unverletzten, wenig belasteten Stelle des Gelenks als Basismaterial. Deren Verwendung führt häufig zu Donormorbidität, zusätzlich produzieren diese Chondrozyten rigiden fibrösen Knorpel anstelle einer flexiblen hyalinen Knorpelmatrix. Der wichtigste restriktive Faktor hier ist die inadäquate Zellzahl, sowie die limitierte Proliferationskapazität differenzierter Chondrozyten in vitro.

Das „tissue engineering“ adulter stromaler Knochenmarkstammzellen bzw. mesenchymaler Stammzellen (MSZ) mit ihrem fast unbegrenzten Proliferationspotential und ihrer chondrogenen Differenzierungskapazität zur Ex-vivo-Generierung von Knorpelgewebe ist noch eine Vision. Denn um MSZ als Chondroprogenitorzellen optimal zu nutzen, ist ein profundes Basiswissen bezüglich ihrer Linienbestimmung, Knorpeldifferenzierungskapazität und der involvierten regulatorischen Faktoren essentiell.

Abstract

Articular cartilage disorders and injuries often result in lifelong chronic pain and compromised quality of life. When it comes to local articular cartilage defects, modern medicine is limited to short-term pain relief and inflammation control. In extreme cases the affected tissue is surgically removed and replaced by a synthetic prosthesis of limited durability. Cell-based therapies to regenerate articular cartilage have been in use since 1994. Such therapies provide a healthy population of cells to the injured site and require differentiated chondrocytes from the uninjured site as base material. Their usage often leads to donor site morbidity and they generate rigid fibrous cartilage where more flexible hyaline cartilage is required. The major restrictive factors for such methods are inadequate number and limited proliferation capacity of chondrocytes in vitro.

Tissue engineering of adult marrow stromal cells/mesenchymal stem cells (MSCs) with their almost unlimited proliferation potential and proven capability to differentiate into chondrocytes for ex vivo generation of cartilage tissue still remains a vision. For optimal harnessing of MSCs as chondroprogenitor cells, basic background information regarding commitment to the lineage, cartilage differentiation and the regulatory factors and molecules involved is essential.

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Grässel, S., Ahmed, N. Einsatz von mesenchymalen Knochenmarkstammzellen für die Ex-vivo-Knorpelregeneration. Orthopäde 36, 227–235 (2007). https://doi.org/10.1007/s00132-007-1058-7

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