The Axolotl Limb Regeneration Model as a Discovery Tool for Engineering the Stem Cell Niche
Purpose of Review
Recent advances in genomics and gene editing have expanded the range of model organisms to include those with interesting biological capabilities such as regeneration. Among these are the classic models of regeneration biology, the salamander. Although stimulating endogenous regeneration in humans likely is many years away, with advances in stem cell biology and biomedical engineering (e.g., bio-inspired materials), it is evident that there is great potential to enhance regenerative outcomes by approaching the problem from an engineering perspective. The question at this point is what do we need to engineer?
The value of regeneration models is that they show us how regeneration works, which then can guide efforts to mimic these developmental processes therapeutically. Among these models, the accessory limb model (ALM) was developed in the axolotl as a gain-of-function assay for the sequential steps that are required for successful regeneration. To date, this model has identified a number of proregenerative signals, including growth factor signaling associated with nerves and signals associated with the extracellular matrix (ECM) that induce pattern formation.
Identification of these signals through the use of models in highly regenerative vertebrates (e.g., the axolotl) offers a wide range of possible modifications for engineering bioinspired, biomimetic materials to create a dynamic stem cell niche for regeneration and scar-free repair.
KeywordsAxolotl Regeneration Regenerative engineering Hyaluronic acid Heparan sulfate ECM
We thank Dr. Susan V. Bryant and Dr. Ken Muneoka for insights into the importance of designing gain-of-function experiments for regeneration, and Dr. Cato Laurencin for his insights into the convergence of regeneration biology and engineering leading to the emergence of regenerative engineering for inducing human regeneration.
Compliance with Ethical Standards
Conflict of Interest
Negar Seyedhassantehrani, Takayoshi Otsuka, Shambhavi Singh, and David M. Gardiner declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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