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Abstract <p>The development of innovative strategies to regrow the amputated limb is a great challenge for human limb loss. The field of regeneration has been extensively studied with remarkable advancement, and many vertebrates were found to have the ability to form and pattern amputated limbs by this mechanism. Regeneration is how an organism replaces lost body parts through various molecular pathways and mechanisms. Retinoic acid (RA) plays a critical role in regeneration by maintaining cell differentiation, proliferation, and other cellular processes. The factors involved in molecular characterization in regeneration processes are a dynamic source for developing regenerative medicines. In axolotl, the role of RA has been studied primarily at the morphological level during epimorphic regeneration. However, in this article, the regulation of several signaling pathways such as <i>wnt</i>,<i> shh</i>,<i> bmp</i>, and <i>Fgf</i> by RA during epimorphic regeneration is briefly and fully summarized. Furthermore, the review fundamentally revolves around the potential of RA as a regenerative medicine to initiate and enhance the mechanisms of regeneration in higher organisms, particularly limb regeneration in humans. The future perspectives in this article will open new avenues for the scientific community to apply RA in higher vertebrates successfully.</p> Lay Summary <p>&#xa0;The development of innovative strategies to regrow the amputated limb is a great challenge for human limb loss. The field of regeneration has been extensively studied with remarkable advancement, and many vertebrates were found to have the ability to form and pattern amputated limbs by this mechanism. Regeneration is how an organism replaces lost body parts through various molecular pathways and mechanisms. Retinoic acid (RA) plays a critical role in regeneration by maintaining cell differentiation, proliferation, and other cellular processes. The factors involved in molecular characterization in regeneration processes are a dynamic source for developing regenerative medicines. In axolotl, the role of RA has been studied primarily at the morphological level during epimorphic regeneration. However, in this article, the regulation of several signaling pathways such as <i>wnt</i>, s<i>hh</i>,<i> bmp</i>, and <i>Fgf</i> by RA during epimorphic regeneration is briefly and fully summarized. Furthermore, the review fundamentally revolves around the potential of RA as a regenerative medicine to initiate and enhance the mechanisms of regeneration in higher organisms; particularly, limb regeneration in humans was discussed.&#xa0;</p> Graphical Abstract <p></p>

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Unlocking the Potential of Retinoic Acid: A Comprehensive Review of Its Regulatory Role in Epimorphic Regeneration in Axolotl Limbs for Regenerative Medicine

  • 期刊论文

  • 发表日期：

    2025年4月2日

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  • Sajad Khan,
  • Khurshid Ahmad,
  • Xiaoshou Liu,
  • Yujun Liang

摘要

Abstract

The development of innovative strategies to regrow the amputated limb is a great challenge for human limb loss. The field of regeneration has been extensively studied with remarkable advancement, and many vertebrates were found to have the ability to form and pattern amputated limbs by this mechanism. Regeneration is how an organism replaces lost body parts through various molecular pathways and mechanisms. Retinoic acid (RA) plays a critical role in regeneration by maintaining cell differentiation, proliferation, and other cellular processes. The factors involved in molecular characterization in regeneration processes are a dynamic source for developing regenerative medicines. In axolotl, the role of RA has been studied primarily at the morphological level during epimorphic regeneration. However, in this article, the regulation of several signaling pathways such as wnt, shh, bmp, and Fgf by RA during epimorphic regeneration is briefly and fully summarized. Furthermore, the review fundamentally revolves around the potential of RA as a regenerative medicine to initiate and enhance the mechanisms of regeneration in higher organisms, particularly limb regeneration in humans. The future perspectives in this article will open new avenues for the scientific community to apply RA in higher vertebrates successfully.

Lay Summary

 The development of innovative strategies to regrow the amputated limb is a great challenge for human limb loss. The field of regeneration has been extensively studied with remarkable advancement, and many vertebrates were found to have the ability to form and pattern amputated limbs by this mechanism. Regeneration is how an organism replaces lost body parts through various molecular pathways and mechanisms. Retinoic acid (RA) plays a critical role in regeneration by maintaining cell differentiation, proliferation, and other cellular processes. The factors involved in molecular characterization in regeneration processes are a dynamic source for developing regenerative medicines. In axolotl, the role of RA has been studied primarily at the morphological level during epimorphic regeneration. However, in this article, the regulation of several signaling pathways such as wnt, shh, bmp, and Fgf by RA during epimorphic regeneration is briefly and fully summarized. Furthermore, the review fundamentally revolves around the potential of RA as a regenerative medicine to initiate and enhance the mechanisms of regeneration in higher organisms; particularly, limb regeneration in humans was discussed. 

Graphical Abstract