Scientific Publications by FDA Staff

J Tissue Eng Regen Med 2018 Mar;12(3):794-807

Limb derived cells as a paradigm for engineering self-assembling skeletal tissues.

Fernando WA, Papantoniou I, Mendes LF, Hall GN, Bosmans K, Tam WL, Teixeira LM, Moos M Jr, Geris L, Luyten FP

Mimicking developmental events has been proposed as a strategy to engineer tissue constructs for regenerative medicine. However, this approach has not yet been investigated for skeletal tissues. Here we demonstrate that ectopic implantation of mouse embryonic day 14.5 long bone anlagen, dissociated into single cells and randomly incorporated in a bioengineered construct, give rise to epiphyseal growth plate like structures, bone, and marrow, which share many morphological and molecular similarities to epiphyseal units that form after transplanting intact long bone anlage, demonstrating substantial robustness and autonomy of complex tissue self-assembly and the overall organogenesis process. We also present in vitro studies that confirm the self-aggregation and patterning capacity of anlage cells and demonstrate that the model can be used to evaluate the effects of large and small molecules on biological behavior. These results reveal the preservation of self-organizing and self-patterning capacity of anlage cells even when disconnected from their developmental niche and subjected to system perturbations such as cellular dissociation. These inherent features make long bone anlage cells attractive as a model system for tissue engineering technologies aimed at creating constructs that have the potential to self-assemble and self-pattern complex architectural structures.