By Jessica Hall on March 24, 2016
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| Transplanted neurons displaying electrical activity. Image credit: Prabhas Moghe, Rutgers via NIH News |
It’s really difficult to convince a mature brain to grow new neurons. Brains tightly control that sort of regulatory function. This difficulty is one of the reasons that prognoses for brain injuries or degenerative brain diseases are so scary; outside the hippocampus or olfactory bulb, once a neuron is gone, its place in the connectome is empty. Treatment options for neurodegenerative diseases or traumatic brain injuries (TBI) are few and unsatisfying. Brains can’t be chemically induced to grow new neurons to replace the old ones. Introducing individual stem cells or neurons in solution doesn’t work: the specific adhesive and signaling connections between neurons are so important that when disrupted by a or stroke, the network can’t recover healthy function faster than its constituent cells die off. Some neurons are stuck together by transmembrane proteins, which means that they can’t be separated without damage, even for transplant.
In light of restrictions like these, scientists wondered whether they might not get better results by introducing intact networks of neurons into damaged brains, rather than individual neurons in isolation. To answer that question, a team led by scientists from Rutgers University created a 3D micro-scaffold, electrospun from polymer fibers and small enough to pass through a standard hypodermic needle, on which they grew neurons before injecting them into brains – where the neuron transplants began to take hold and flourish.
The researchers first cultured human neurons by converting mature adult cells like skin cells back into pluripotent stem cells, then chemically inducing their development into neurons. Then they seeded the new neurons into the fibrous 3D polymer scaffold. To explore the reasons that this technique might succeed or fail, the researchers experimented by varying the thickness of the fibers they used to construct the scaffold, and the distance between them. Thicker fibers ended up performing the best, lending credence to the idea that neurons need to be close enough that they can link up with other nearby neurons, but not crammed in so close that there’s no room for synapses to form and change. “If the scaffolds were too dense, the stem cell-derived neurons were unable to integrate into the scaffold, whereas if they are too sparse then the network organization tends to be poor,” explains Prabhas Moghe, Ph.D., co-senior author of the paper.
After keeping the cells in culture for a few weeks, the scientists observed the development of small neuronal networks within the polymer scaffold — networks that the team went on to inject directly into slices of mouse brain, but also into the striatum of the brains of living mice. The researchers found that the scaffolded, interconnected neurons survived much better than individual neurons when injected into the mouse brains, on the order of a 40-fold improvement. Furthermore, the scaffolded neurons exhibited electrical activity and better outgrowth in the mouse brains, and once they were ensconced the transplanted neurons began to express proteins important to the formation of synapses – a solid indication that the transplanted cells could integrate themselves into the host brain tissue.
The authors have a clear vision of what they want to do with this technology. Their goal is to develop methods to induce stem cells to differentiate into excitatory dopaminergic neurons: the type of neuron that degenerates in people with Parkinson’s disease. The supporting work will involve fine-tuning the materials and behavior of these micro-scaffolds to better safeguard the development of dopamine-producing neurons, and finding the best mouse models of the disease to test their transplant therapy.
http://www.extremetech.com/extreme/225320-lab-grown-neuronal-network-transplants-could-treat-brain-diseases-like-parkinsons
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