Lab-Created Miniature Brains Grow Their Own Blood Vessels

A fluorescent stained cross-section image of a vascularized brain organoid, showing a vessel that has grown into the central layers of tissue. Pham et. al/NeuroReport, 2018

Aliyah Kovner 04 Apr 2018, 23:31

Back in 2013, scientists first developed the techniques necessary to grow three-dimensional clumps of brain cells – called brain organoids – in a laboratory setting, allowing an unprecedented look at how human neurons develop and form connections.

Now, a team of researchers from the Institute for Regenerative Cures and the University of California Davis has taken the neural model to the next level in terms of resembling a true brain: Their organoids are the first to successfully grow oxygen-supplying blood vessels.

“The whole idea with these organoids is to one day be able to develop a brain structure the patient has lost made with the patient’s own cells,” lead author Ben Waldau told Wired. Creating an organoid with its own blood supply enables them to grow larger and survive longer in an artificial culture setting, and also makes integration into a patient’s existing brain tissue more likely.  

“We see the injuries still there on the CT scans, but there’s nothing we can do. So many of them are left behind with permanent neural deficits – paralysis, numbness, weakness – even after surgery and physical therapy.”

As described in NeuroReport, the team took brain cells from one of their patients during surgery and converted them into induced pluripotent stem cells. These undifferentiated cells were prompted to mature into brain precursor cells and endothelial cells, the cell type that forms the lining of blood and lymphatic vessels.

After the brain cell clusters grew on their own for 34 days, the nascent organoid was covered in 250,000 endothelial cells, embedded in a protein-rich gel, and incubated for three to five weeks. During this period of development, the organoids differentiated and self-assembled into mini-brains complete with the full roster of brain cell types, and an organizational complexity that, according to Wired, is nearing that of a second-trimester fetal brain (but is only about 3.5 mm, or 0.14 inches in size).

Most crucially, the organoids sprouted an impressive grid of seemingly normal blood vessels on the exterior of the cluster, several of which wove themselves deep into the folds of brain cells.

In a parallel experiment, some of the endothelial-covered organoids were surgically implanted into a mouse brain, rather than continuing to grow in the protein gel. After two weeks in vivo, the brains were retrieved and examined. Amazingly, these organoids were still alive and had also grown a network of blood vessels.

More in-depth studies of vascularized organoids will no doubt be coming soon, and, like earlier mini brains, will be put to work modeling diseases such as microcephaly, autism, and schizophrenia.

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A stained image of a non-vascular brain organoid developed by UCLA researchers to study microcephaly caused by Zika virus. UCLA Broad Stem Cell Research Center/Cell Reports

 

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