Research ArticleBIOMATERIALS

Human Mesenchymal Stem Cell–Derived Matrices for Enhanced Osteoregeneration

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Science Translational Medicine  02 May 2012:
Vol. 4, Issue 132, pp. 132ra55
DOI: 10.1126/scitranslmed.3003396

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Matrix at Its Best

Stem cells may have the powers of healing. Bone, that is. Yet, designing the optimal treatment to produce a controlled regenerative effect has been challenging. Simply said, one cannot just fill a defect with stem cells and expect miraculous outcomes every time. Recognizing this, Zeitouni and colleagues paid close attention to the time course of healing after injury to mouse bone, to see how this affects the growth and bone-generating potential of mesenchymal stem cells (MSCs). Efficacy, as it turns out, is limited to an “osteogenic (bone-producing) phase,” which can be prolonged by administering the cells along with an extracellular matrix (ECM) produced by the MSCs themselves.

Bone heals in three general stages: inflammation, regeneration, and remodeling. In non-union defects in mouse calvaria, the authors showed that human MSCs were able to repair bone immediately after inflammation, but lost all bone-healing abilities upon entering the remodeling phase. Unfortunately, this restricts bone healing to a small time window that could lead to variable outcomes. To avoid this, Zeitouni et al. prepared a scaffold containing human MSCs that had been treated with GW9662—a small molecule that directs stem cells down bone-related lineages—as well as ECM derived from MSCs. This cell-scaffold approach extended the time window for healing, resulting in 80 to 100% healing of a bone lesion after 3 weeks, compared to 30 and 60% healing in the MSC- and GW-MSC–only treatment groups, respectively. The authors suggest that collagens in the ECM derived from osteogenic MSCs might be responsible for enhancing bone repair. Although tweaking microenvironmental cues may be the key to non-union bone healing in people, the authors will need to test in larger animal models and for longer periods of time to ensure reproducible effects of human MSCs and their ECMs.

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