Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb.
Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb.
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DOI：
10.1016/j.celrep.2018.10.010
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发表时间：
2018-11-06
期刊：
影响因子：
8.8
通讯作者：
Levin M
中科院分区：
文献类型：
--
作者：
Herrera-Rincon C;Golding AS;Moran KM;Harrison C;Martyniuk CJ;Guay JA;Zaltsman J;Carabello H;Kaplan DL;Levin M
成年脊椎动物肢体修复的诱导是一个迫切而尚未解决的问题。在这里，我们的特点是一个集成的设备，提供药物的成年非洲爪蟾，通常再生软骨尖峰截肢后切断后肢的影响。一个可穿戴的生物反应器，含有丝蛋白为基础的水凝胶，提供孕酮后立即后肢截肢仅24小时的伤口部位诱导再生的桨状结构在成年青蛙。分子标记，形态分析，X射线成像，免疫荧光和行为测定被用来表征成功的再生和hypomorphic穗，在未经处理的动物生长的桨状结构之间的差异。我们的实验建立了一个模型，用于测试治疗鸡尾酒在脊椎动物后肢再生，确定促再生活性的甾醇含有生物反应器，并提供了原则的证明，短暂使用集成的基于设备的小分子药物的交付作为一个可行的策略，以诱导和维持长期的再生反应。脊椎动物肢体的复杂性推动了对引发内源性修复过程的再生治疗的研究。Herrera-Rincon等人表明，一种含有孕酮的可穿戴生物反应器，仅应用24小时，就能诱导青蛙非洲爪蟾（Xenopus laevis）截肢后肢的再生生长和图案形成。
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. The complexity of vertebrate limbs drives the search for regenerative treatments that trigger endogenous processes of repair. Herrera-Rincon et al. show that a wearable bioreactor containing progesterone, applied for only 24 hr, induces months of regenerative growth and patterning of amputated hindlimbs in the frog Xenopus laevis.
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影响因子：
3.3
作者：
Levin M
通讯作者：
Levin M
影响因子：
3.6
作者：
DIROSA, I;PANARA, F;PASCOLINI, R
通讯作者：
PASCOLINI, R
影响因子：
2.2
作者：
Hechavarria, Daniel;Dewilde, Abiche;Kaplan, David L.
通讯作者：
Kaplan, David L.
DOI：
10.1073/pnas.220302597
发表时间：
2000-11-07
影响因子：
11.1
作者：
Bayaa, M;Booth, RA;Liu, XJ
通讯作者：
Liu, XJ
影响因子：
3.7
作者：
Golding, Anne;Guay, Justin A.;Kaplan, David L.
通讯作者：
Kaplan, David L.