Appendage Regeneration in Adult Vertebrates and Implications for Regenerative Medicine
Jeremy P. Brockes* and
Anoop Kumar
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
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Fig. 1. Schematic of three approaches to regenerative medicine. (A) Implantation of stem cells (light green) from culture leads to the restoration of the structure. (B) Stem cells are provided with a scaffold (triangle) in order to guide restoration. (C) The residual cells of the structure are induced to make a regenerative response.
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Fig. 2. Scaling differences in limb regeneration and development. (A) An adult newt (Notophthalmus viridescens) limb blastema (left) (arrowheads mark the original plane of amputation) next to a newt embryo (right) showing the developing limb bud (arrowed). The specialized epithelium surrounding the blastema is called the wound epidermis. (B) An adult axolotl limb blastema (left) (from an animal 16 cm in length) next to a 4-cm larval axolotl limb blastema (right) (arrowheads mark the amputation plane). The scale bars apply to the pair of (A) or (B) images, respectively.
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Fig. 3. Morphogenetic autonomy and its implications for regeneration. (A) A limb blastema from a salamander transplanted to the fin tunnel. (B) The limb structures formed from the blastema of (A). (C) Repair of a bone gap by grafting an artificial scaffold seeded with stem cells; an example of the approach of Fig. 1B. (D) Repair of a bone gap in a salamander by formation of a blastema and subsequent autonomous reconstruction of the distal skeletal elements.
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Fig. 4. Prod 1/CD59 as a local cue for PD identity in limb regeneration. (A) The graded expression of Prod 1 mRNA along the PD axis in adult newt limb (outlined in red) is shown relative to the level in the hand (red points), whereas the expression in P and D blastemas is shown after amputation (green points) at the levels arrowed. (B) Expression of Prod 1 mRNA in P and D blastemas confronted in culture. (C) Expression of Prod 1 protein in confronted P and D blastemas. Scale bars in (B) and (C), 200 µm. (D) Elevated expression of Prod 1 converts distal blastemal cells to proximal. The left limb blastema of a larval axolotl (upper) was electroporated so as to express red fluorescent protein, and after regeneration, the labeled cells contribute to the hand. The right blastema (lower) was electroporated to express green fluorescent protein and Prod 1, and cells contribute to proximal tissue after regeneration, even to tissue proximal to the amputation plane (dashed line). Scale bars in the left panel, 200 µm; in the right panel, 1 mm. For experimental details, see (89). (B) and (C) are from (33) and (D) is from (28), with permission.
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