The Niche

ISSCR plenaries: how to repair 1) a salamander leg and 2) a human airway

NOTE: These two write-ups are by Teisha Rowland, a volunteer Niche blogger and student at UC Santa Barbara.

Limb regeneration takes nerve

Proper limb regeneration in the salamander requires the presence and function of nerves, although it is unclear why this is on a molecular level. Recent evidence implicates a newly discovered protein as having a central role in the innervation of regenerating limbs.

At ISSCR in Barcelona, Jeremy Brockes of the University College London reported that in severed salamander limbs the protein n(ewt)AG, or nAG, is key for promoting regeneration. nAG production, in turn, is linked to nerves in severed limbs.


When a salamander limb is cut, the injured site forms a blastema, cells that regenerate the lost limb. nAG is also expressed at the blastema. If nerves are removed, nAG expression stops, and the limb does not regenerate. However, regeneration does occur if nAG is supplied to the injury site. Surprisingly, though, nerves are not required for limb development: limbs can be manipulated to form without a nerve supply, and these are capable of regeneration.

Brockes’ work supplied an explanation for this apparent paradox, with the nervous system acting to coordinate limb regeneration. During development, nAG expression is high but then declines when limbs are innervated. The abnormal limbs that never become innervated retain high levels of nAG. Brocke concluded that axons may regulate the decrease in nAG in limbs after innervation, and also the increased nAG expression in amputated limbs. Overall, Brocke revealed a significant link between the nervous system and, ultimately, regulation of limb regeneration.

Session info

Speaker: Jeremy Brockes

Talk title: Mechanisms Underlying Limb Regeneration in an Adult Vertebrate(Friday, Plenary Session VI)

Broken airway mended with patient’s own cells

In a first for regenerative medicine, a patient’s own stem cells have been bioengineered into a functional bronchus and successfully grafted into the patient. The patient had a near-collapsed left bronchus. Though it is usually quite difficult to fix large pieces of damaged airways, after several other approaches did not work, that option seemed the most likely to help the patient, explained clinician-researcher Paolo Macchiarini of the Hospital Clinico de Barcelona, Spain. As a replacement bronchus, researchers obtained a human trachea segment from a cadaveric donor. To protect the segment from immune rejection, all cells and major histocompatibility complexes were removed. The stripped trachea was then incubated in a bioreactor with the patient’s cells: epithelial cells were seeded inside the trachea and mesenchymal stem cell-derived chondrocytes outside. The bioengineered bronchus was transplanted into the patient and became indistinguishable from normal bronchus tissue after one month. Soon after, the tissue displayed completely normal function. Macchiarini suggests that, in future, the body could be used as its own bioreactor to simplify this process. Thus, he says, the secret for accelerating regenerative medicine might literally be within patients.

See links to previous coverage of this work on the Niche and the Great Beyond, plus an account of getting the stem cells from the UK to Spain on a private plane when EasyJet refused.

Session info

Speaker: Paolo Macchiarini

Talk title: Role and Fate of Autologous Cells in Whole Tissue Engineered Airway Replacement

(Friday, Plenary Session VI)

This account is by Teisha Rowland, a student at UC Santa Barbara who uses hESCs and iPSCs. She runs a blog called allthingsstemcell.com

Note from Niche editor This post comes as a response to my solicitation in June calling for people to submit their accounts of ISSCR 2009. I’d asked people to describe what most interested them and to disclose any conflicts of interest. I’m very grateful for these volunteers’ help making more information available.

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