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Cell Rep January 1, 2018; 25 (6): 1593-1609.e7.

Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb.

Herrera-Rincon C , Golding AS , Moran KM , Harrison C , Martyniuk CJ , Guay JA , Zaltsman J , Carabello H , Kaplan DL , Levin M .

The induction of limb repair in adult vertebrates is a pressing, unsolved problem. Here, we characterize the effects of an integrated device that delivers drugs to severed hindlimbs of adult Xenopus laevis, which normally regenerate cartilaginous spikes after amputation. A wearable bioreactor containing a silk protein-based hydrogel that delivered progesterone to the wound site immediately after hindlimb amputation for only 24 hr induced the regeneration of paddle-like structures in adult frogs. Molecular markers, morphometric analysis, X-ray imaging, immunofluorescence, and behavioral assays were used to characterize the differences between the paddle-like structures of successful regenerates and hypomorphic spikes that grew in untreated animals. Our experiments establish a model for testing therapeutic cocktails in vertebrate hindlimb regeneration, identify pro-regenerative activities of progesterone-containing bioreactors, and provide proof of principle of brief use of integrated device-based delivery of small-molecule drugs as a viable strategy to induce and maintain a long-term regenerative response.

PubMed ID: 30404012
PMC ID: PMC6317729
Article link: Cell Rep
Grant support: [+]

Species referenced: Xenopus
Genes referenced: acta2 ctrl itih3

GEO Series: GSE118454: NCBI

Article Images: [+] show captions
References [+] :
Adams, Light-activation of the Archaerhodopsin H(+)-pump reverses age-dependent loss of vertebrate regeneration: sparking system-level controls in vivo. 2013, Pubmed, Xenbase