Epimorphic regeneration of the mouse digit tip is finite

Connor P. Dolan, Tae Jung Yang, Katherine Zimmel, Felisha Imholt, Osama Qureshi, Alyssa Falck, Joshua Gregory, Macie Mayes, Kayla Ritchie, Hannah Koester, Benjamin Daniel, Mingquan Yan, Ling Yu, Larry J. Suva, Dana Gaddy, Lindsay A. Dawson, Ken Muneoka, Regina Brunauer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Structural regeneration of amputated appendages by blastema-mediated, epimorphic regeneration is a process whose mechanisms are beginning to be employed for inducing regeneration. While epimorphic regeneration is classically studied in non-amniote vertebrates such as salamanders, mammals also possess a limited ability for epimorphic regeneration, best exemplified by the regeneration of the distal mouse digit tip. A fundamental, but still unresolved question is whether epimorphic regeneration and blastema formation is exhaustible, similar to the finite limits of stem-cell mediated tissue regeneration. Methods: In this study, distal mouse digits were amputated, allowed to regenerate and then repeatedly amputated. To quantify the extent and patterning of the regenerated digit, the digit bone as the most prominent regenerating element in the mouse digit was followed by in vivo µCT. Results: Analyses revealed that digit regeneration is indeed progressively attenuated, beginning after the second regeneration cycle, but that the pattern is faithfully restored until the end of the fourth regeneration cycle. Surprisingly, when unamputated digits in the vicinity of repeatedly amputated digits were themselves amputated, these new amputations also exhibited a similarly attenuated regeneration response, suggesting a systemic component to the amputation injury response. Conclusions: In sum, these data suggest that epimorphic regeneration in mammals is finite and due to the exhaustion of the proliferation and differentiation capacity of the blastema cell source.

Original languageEnglish
Article number62
JournalStem Cell Research and Therapy
Issue number1
StatePublished - Dec 2022
Externally publishedYes


  • Amputation
  • Positional information
  • Regeneration
  • Stem cells


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