Skin cells to dopamine neurons, no stem-cell stage

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Massimiliano Caiazzo, Vania Broccoli and colleagues (San Raffaele Institute, Milan; Nature 476:224–227; Telethon funding listed). Ulrich Pfisterer, Malin Parmar and colleagues (Lund University; PNAS 108:10343–10348; Lundbeck Foundation funding listed).

What happened

Induced stem cells (landmark 32) are made by taking cells back to a stem-cell state, and leftover stem cells can form tumours. In 2011 two groups skipped that stage.

• Caiazzo et al. Three factors, Ascl1, Nurr1 and Lmx1a, converted mouse and human fibroblasts into neurons that make and release dopamine and fire regular pacemaker-like spikes. It worked with cells from healthy donors (fetal and adult) and from people with Parkinson's.
• Pfisterer et al. Ascl1, Brn2 and Myt1l turned human fibroblasts into neurons. Adding Lmx1a and FoxA2 steered them toward a dopamine identity: about 10% of the converted neurons, per the paper's discussion. The paper did not measure dopamine release or test grafts in animals.

Why it moved us toward a cure

It offered a second route to replacement cells beyond stem-cell-derived neurons (landmark 32), and later work tried the same idea inside the brain by converting local cells (landmark 75). Suggested new parent link: 214 should be a parent of 75.

Outcome

Open. This remains a laboratory technique; I found no human trial. Caiazzo's efficiency is not in the abstract, and in-brain conversion claims later became disputed (landmark 75). PubMed lists commentary only; no correction or retraction was found for either paper.

Sources

• Caiazzo et al., Nature 2011;476:224–227, DOI 10.1038/nature10284, PMID 21725324 (abstract read via Europe PMC)
• Pfisterer et al., PNAS 2011;108:10343–10348, DOI 10.1073/pnas.1105135108, PMID 21646515 (PMC full text read)
• Not yet verified: Caiazzo's conversion efficiency; whether Caiazzo's cells survive and work in animal grafts; any clinical programme; PubPeer not checked.