The bone-ligament interface is a complex structure that transmits forces through zones of bone, fibrocartilage, and ligament. Human mesenchymal stem cells (hMSCs) offer potential as a single, autologous cell source for restoration of the bone-ligament interface after ligament reconstruction due to their ability to differentiate into osteoblasts, chondrocytes, and ligament/tendon fibroblasts. However, conditions leading to ligamentogenic differentiation of hMSCs are not well established. Here, we aim to identify in vitro conditions that promote the ligamentogenic differentiation of hMSCs.  We hypothesize that a combination of microenvironment cues found during ligament development, including growth factor and integrin binding and cell-cell junctions, play a critical role in this differentiation lineage. Towards this, we have isolated and characterized hMSCs from bone marrow and screened the effects of soluble and tethered microenvironment cues on their ligamentogenic differentiation.  Specifically, hMSCs have been cultured with bone morphogenic protein-12 (BMP-12) and bone morphogenic protein-13 (BMP-13), and the effect of these soluble cues on ligament-related gene expression and protein production has been assessed. Further, we have synthesized poly(ethylene glycol) hydrogels with thiol-norbornene photopolymerization as a blank slate culture system on which cell adhesion and orientation can be controlled. Using these hydrogels, we have examined the effects of collagen-related integrin-binding sequences on hMSC gene expression and protein production.  We aim to use the results of these studies towards the development of a hMSC delivery system for bone-ligament interface regeneration.

Directing mesenchymal stem cell differentiation in controlled microenvironments towards enhanced ligament reconstruction and regeneration

247th National Meeting (2014)

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