March 25, 2010

Follow ups on Organ Printing and Nanoparticle Delivery of RNA in Humans

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1. HPLus Magazine has a follow up on the organ printing work of Organovo and Invetech

The bioprinter relies on stem cells, extracted from adult bone marrow and fat, as precursors. Using appropriate growth factors, the stem cells can be differentiated into other types of cells. The cells are formed into droplets 100-500 microns in diameter and containing 10,000-30,000 cells each. The droplets retain their shape well and pass easily through a process not that different than the inkjet printer on your desk: propelling variably-sized droplets of liquid onto a page.

A second print head deposits a sugar-based, biofriendly hydrogel scaffold that supports but does not interfere with or stick to the cellular droplets. The hydrogel-droplet structure is left for a day or two, to allow the cellular droplets to fuse together. Once the tissue has formed, the hydrogel is removed. Here’s a video that shows the inkjet process fabricating a 3D biocompatible hydrogel tube in which living cells can be embedded.

Bioprinters may one day be capable of printing tissues and organs not just for use by surgeons, but directly into the body. Dr. Atala is currently working on the design for a bioprinter that would scan the contours of a body part requiring a skin graft and then print skin onto it. As for bigger body parts, Organovo’s Dr. Forgacs thinks they may ultimately come in different shapes and sizes — designer organs.

2. Derek Lowe who writes the Corante blog has a clearer explanation of the recent success in delivering RNA to tumors in humans.

A highly engineered system like this addresses several problems at once: how do you keep the RNA you're dosing from being degraded in vivo? (Wrap it up in a polymer - actually, two different ones in spherical layers). How do you deliver it selectively to the tissue of interest? (Coat the outside with something that tumor cells are more likely to recognize). How do you get the RNA into the cells once it's arrived? (Make that recognition protein is something that gets actively imported across the cell membrane, dragging everything else along with it). This system had been tried out in models all the way up to monkeys, and in each case the nanoparticles could be seen inside the targeted cells.

is this therapy doing the patients any good? Unfortunately, the trial results themselves are not out yet, so we don't know. That two-out-of-three uptake rate, although a pretty small sample, could well be a concern. The only between-the-lines inference I can get is this: the best data in this paper is from patient C, who was the only one to do two cycles of nanoparticle therapy. Patient A (who did not show uptake) and patient B (who did) had only one cycle of treatment, and there's probably a very good reason why. These people are, of course, very sick indeed, so any improvement will be an advance. But I very much look forward to seeing the numbers.


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