# Stimulating regeneration in mouse limbs

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $313,880

## Abstract

PROJECT SUMMARY
Mammals, including humans, are generally considered to have lost the capacity to regenerate their limbs after
amputation. However, both human and mouse are able to regenerate the extreme tip of their digits through a
true regeneration response similar to that observed in amphibians. This regeneration response establishes the
foundation on which we can explore methods to stimulate more extensive regeneration in humans. The mouse
digit is a good mammalian model because its regeneration process closely resembles that in humans. The
extreme distal tip can regenerate via the formation of a bud of undifferentiated cells (a blastema). But
amputations and injuries in more proximal level of the digits and limbs usually result in scar wounding. In these
clinically more important situations, the inability of blastema formation is the biggest barrier for successful
regeneration. In our studies on limb regeneration in the anuran amphibian, Xenopus laevis, and on the
normally non-regenerating middle phalanx amputations in mouse, we have demonstrated that transplantation
of a fibrin matrix containing limb progenitor cells, in the presence of additional growth factors, can stimulate
regeneration of a complete limb in Xenopus and regrowth of bone in mouse digits. However, the overall
regeneration of the amputated digit in mouse is still limited. In this project we propose to achieve good
regeneration by constructing a vascularizable 3D fibrin scaffold to mimic a regeneration blastema for
transplanting to the digit stump after middle-phalanx amputation. We will generate specific progenitor cells from
iPS cell lines established in our labs and engineer a 3D fibrin scaffold for transplantation to test our hypothesis
that a mimicking regeneration blastema can stimulate regeneration. We will determine the optimal conditions
for constructing a regeneration-stimulating matrix and investigate the tissue interactions between the host and
donor and within the donor scaffold. The outcome of this project will establish an approach for stimulating digit
regeneration, with the engineering of a transplantable, re-vascularizable 3D scaffold containing a combination
of multiple types of progenitor cells and growth factors. Since the cell supply is based on iPS cells, a
successful outcome will lead directly to the ability to make similar transplants for repair of human digit and limb
injuries.

## Key facts

- **NIH application ID:** 9977769
- **Project number:** 5R01HD084440-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** James R. Dutton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $313,880
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977769

## Citation

> US National Institutes of Health, RePORTER application 9977769, Stimulating regeneration in mouse limbs (5R01HD084440-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9977769. Licensed CC0.

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