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Sci Adv January 28, 2022; 8 (4): eabj2164.
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Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis.

Murugan NJ , Vigran HJ , Miller KA , Golding A , Pham QL , Sperry MM , Rasmussen-Ivey C , Kane AW , Kaplan DL , Levin M .

Limb regeneration is a frontier in biomedical science. Identifying triggers of innate morphogenetic responses in vivo to induce the growth of healthy patterned tissue would address the needs of millions of patients, from diabetics to victims of trauma. Organisms such as Xenopus laevis-whose limited regenerative capacities in adulthood mirror those of humans-are important models with which to test interventions that can restore form and function. Here, we demonstrate long-term (18 months) regrowth, marked tissue repatterning, and functional restoration of an amputated X. laevis hindlimb following a 24-hour exposure to a multidrug, pro-regenerative treatment delivered by a wearable bioreactor. Regenerated tissues composed of skin, bone, vasculature, and nerves significantly exceeded the complexity and sensorimotor capacities of untreated and control animals'' hypomorphic spikes. RNA sequencing of early tissue buds revealed activation of developmental pathways such as Wnt/β-catenin, TGF-β, hedgehog, and Notch. These data demonstrate the successful "kickstarting" of endogenous regenerative pathways in a vertebrate model.

PubMed ID: 35080969
Article link: Sci Adv
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: etv1 hpse il1b kit notch1 ptgs2 sall4 shh ski sox2 tgfb1
GO keywords: limb morphogenesis [+]

Article Images: [+] show captions
References [+] :
Alibardi, Review: Limb regeneration in humans: Dream or reality? 2018, Pubmed