Research team used 3D scaffold technology to develop regenerative neural tissue therapy
Science tells us that neurons rarely regenerate, and if they do, it is at a painfully slow rate.
“Something that seems so far-fetched in science fiction is something that we are able to discover in labs right upstairs where I take my classes,” said Sreerama Gollakota, a School of Engineering junior.
Neural tissue regeneration, which was once the stuff of fiction, is coming to reality.
With Prabhas V. Moghe, a distinguished professor in the Department of Biomedical Engineering, at the helm, staff and students are currently searching for a way to regenerate and reintegrate neurons.
“Could it be possible to conceive a way to transplant healthy human neurons into the brain?” Moghe said.
This is what he describes as the “key unmet need,” the discovery of which is the first part of the research process. After this, scientists write grant proposals, secure funding, put a team in place and finally perform the research.
These transplanted neurons will serve as a regenerative tissue therapy which Moghe and his team specifically created to target Parkinson’s disease, a neurodegenerative disease.
Parkinson’s disease causes the deterioration of neurons that produce dopamine, causing “symptoms such as tremor, slowness, stiffness, and balance problems,” according to Mayfield Clinic.
For this reason, Moghe’s lab focused on producing dopamine-secreting neurons and reintegrating them into the brain.
“When neurons are damaged, diseased or afflicted, you have various pharmacotherapies or drugs that really address very single symptoms of the problem … but there is no comprehensive way to fix the problem,” he said.
An oft-tested solution has been to replace these neurons completely instead of treating the patient with solely drugs or pharmacotherapies.
Traditionally, scientists have grown neurons in a dish, cut them up and then injected them into the brain, Moghe explained. However, even if the neurons do survive, this method does not cause the neurons to attach to the desired location in the brain.
“Neurons really survive as a colony, as a network,” he said. To produce this network, the neurons need a scaffold to which they can attach and spread.
The goal was to design a bio-compatible, non-immunogenic and highly permissive three-dimensional scaffold onto which one can produce these human neurons, he said.
The term “three-dimensional” means that the transplanted scaffold grows and integrates into the area it is placed, interacting, in this case, with other neurons, according to a paper published on NCBI.
“There’s a twofold mission here: to produce and reprogram human neurons, and as you grow them in very close contact with each other on this (3D) scaffolding, the idea is that they would form fruitful connections with each other,” Moghe explains.
In the past, scientists have used fetal stem cells to produce neurons. To avoid this, Moghe thought to use adult somatic cells.
He does this by using human Induced Pluripotent Stem Cells (iPS).
The idea is to take a skin cell, for example, and engineer the cell with certain genes, he explained. These genes will send the cell back into its somewhat primordial state, which is the state in which it infinitely propagates into multiple lineages, or multiple cell types.
“What’s cool is that this conversion from a stem cell into a neuron is done in this (3D) scaffold. So the scaffold is not just there as a bridge or a carrier to take the cells into the brain, but rather as a platform onto which you’re performing this reprogramming and this conversion into the neurons,” he said.
The 3D scaffolds are produced through electrospinning technology, produced in the New Jersey Center for Biomaterials. Electrospinning creates a matt of bio-safe, bio-compatible polymers.
Moghe said to “imagine producing a thick weave, each fiber in the order of a few microns or micrometers.”
This matt is then split into separate “islands” and then injected into the brain.
They have seen a “one-hundred fold increase in how viable (these neurons) are in the brain” versus when they were injected without any scaffolding or network.
Moghe’s lab currently tries to increase the elasticity of the scaffold technology so that it matches that of the brain. Biopolymers are “not mechanically of the same softness, compliance or elasticity that you need in a soft organ like the brain,” he said.
For this reason, they attempt to use a peptide-based scaffold to form soft hydrogel microspheres, which have a high water content and provide a cushion for the neurons.
“We’re creating these microspheres that have neurons trapped between them at high densities, and now they’re in a soft material,” Moghe said.
Moghe also hopes to make the conversion of stem cells to neurons safer by using chemical methods, which will reduce the neurons’ interactions with viruses.
Although Moghe’s lab can be classified under biomedical engineering, he emphasizes the interdisciplinary nature of the lab environment in terms of its constituents’ educational backgrounds, across experience level and majors.
He specifically mentions three women in his lab: Biomedical Engineering post-doctorate Nicola Francis, chemical engineering graduate student Nanxia Zhou, and molecular biology and biochemistry first year Hannah Calvelli.
Francis adds that Director Rick Cohen and Astha Saini, his undergraduate researcher, from the Stem Cell Institute of New Jersey as well as Dr. Zhiping Pang, her other primary investigator from the Child Health Institute of New Jersey, have also been valuable collaborators.
Francis is officially a research associate for this project, and has her appointment through The Child Institute of New Jersey. She developed and brought this hydrogel and microfluid technology to Moghe’s lab.
“There’s multiple projects in the lab that are highly different from each other, and there’s a great spirit of collaboration and scientific work,” she said.
“At this point I do everything myself … and I train students to also be involved in all areas as well. No one is going to specialize in any one thing, I want everyone to be well-rounded and be able to do any of the tasks needed to complete the project,” she said.
Calvelli first became interested in Moghe’s lab because of its focus on medicine, something she wanted to learn about through research.
“I was a little worried at first because being an undergrad in a different field, that was really intimidating, but Nicola and Nanxia have been my mentors throughout the process and they’re both really good at teaching and trying to explain everything step-by-step,” she said.
“Sometimes people might need things explained a different way, but after working on the same project for a while you learn the jargon in that particular field,” Francis said.
Francis also notes that out of the 10 or 15 people who work in this lab, majority are women, with only a “handful” of men. She says that in all her lab experience at least half of her team members have been women, and she has had many women advisors as well.
Calvelli adds, “I think it’s pretty empowering especially because research is a male-driven field so it’s definitely nice to work with a lot of strong women who are passionate about STEM.”
She recommends undergraduate research and said, “Rutgers has so much opportunity for undergraduate research, it’s definitely something you should try out and they have it for really every field, even outside of STEM.”