202210 Opportunities for Advancing Limb Regeneration Research

​Program seeks Council approval for a new initiative titled ‘Opportunities for Advancing Limb Regeneration Research’.

This initiative addresses the Aspirational Goal in the NICHD Strategic Plan titled advancing the ability to regenerate human limbs by using emerging technology to activate the body’s own growth pathways and processes.  It aims to promote targeted transformational basic research on topics that were identified by the research community from 1) a Request for Information (RFI), published in January 2020 and 2) a workshop, organized by the Developmental Biology and Structural Variation Branch (DBSVB) and the National Center for Medical Rehabilitation Research (NCMRR) of NICHD, held in February 2021.

Each year, about 1 in every 1,900 babies in the United States are born with a limb defect and an additional 1.6 million people incur limb injury and/or amputation.  Some lower order vertebrates such as salamanders and newts have the ability to regrow severed limbs through a process called epimorphic regeneration.  In contrast, regeneration appears to be severely limited in higher level vertebrates.  In mammals, for example, wound healing in response to injury typically leads to scarring/fibrotic tissue formation, rather than regeneration.  The epimorphic regeneration process occurs through the formation of a blastema, a process that includes dedifferentiation, trans-differentiation, migration of adult stem cells to the site of injury and other morphogenetic events permissive of proper tissue growth and patterning.  Although the process has been investigated in many labs using a variety of models and approaches, the identity of key regulators of wound repair and regeneration remain unknown.  The current state of the science suggests that focused investment in research on key aspects of epimorphic regeneration is necessary for developing strategies to regenerate limbs in higher vertebrates and mammals including humans. 

Based on the state of the science and technological advances informed by the RFI and the workshop, DBSVB proposes to promote transformative basic research in animal models to address those gaps that can be attained as near-term goals.  These include but are not limited to: 1) promoting basic research with innovative strategies focused on identifying key regulatory mechanisms that can be manipulated to drive limb regeneration in animal models recapitulating human conditions of developmental limb deficiencies and 2) addressing challenges in human amputees that can be addressed in the near term using animal models, such as promoting wound healing without scarring and accelerating muscle regeneration to compensate for the extensive muscle loss that occurs at the site of injury or amputation.

In summary, to directly address an aspirational goal of the NICHD Strategic Plan, the proposed initiative is primarily focused on gaining insight on the body’s own growth pathways and processes that can be manipulated to promote limb regeneration in higher vertebrates (including mammals) that might otherwise lack the capacity for regeneration.

Program Contact

Mahua Mukhopadhyay
Developmental Biology and Structural Variation Branch (DBSVB)

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