New Way of Manipulating Stem Cells Leads to Healthy Nerve Cells in Animal Study

Scientists have created a special matrix that allowed them to differentiate stem cells into nerve cells that, when transplanted into a rat model of Parkinson’s disease, eased the animals’ symptoms by replacing those nerve cells lost to the disease.

This matrix is also able to stimulate differentiation of stem cells, prodding them to become nerve cells, without a need for growth factors thought to raise a cancer risk in treated patients.

Their study, “Extracellular Nanomatrix‐Induced Self‐Organization of Neural Stem Cells into Miniature Substantia Nigra‐Like Structures with Therapeutic Effects on Parkinsonian Rats,” was published in the journal Advanced Science.

Parkinson’s is characterized by the gradual loss of dopamine-producing nerve cells in the substantia nigra, a region of the brain responsible for movement control.

Stem cell therapy — which involves growing and differentiating stem cells into specific types of cells — is among the most promising of those treatments seeking to cure Parkinson’s, due to its potential to replace dopaminergic nerve cells lost in the course of the disease.

However, its potential has been hindered by a series of technical challenges, including the type and large number of materials (e.g., growth factors) required, the long time period necessary, and a low efficiency.

The use of growth factors to promote stem cell differentiation is particularly troubling, as these factors may also stimulate the growth of cancer cells after a transplant.

“Currently, an effective method to induce the rapid and specific differentiation of [stem cells] into [nerve cells] without applying traditional GFs [growth factors] is lacking. Such a method is urgently needed to enable the development of [stem cell] therapies that may ultimately cure PD [Parkinson’s disease],” the researchers wrote.

A team at Hong Kong Baptist University (HKBU) created a special matrix material that can stimulate the growth and differentiation of nerve cell progenitors into miniature substantia nigra-like structures, or mini-SNLSs. These mini-SNLSs contain the dopamine-producing nerve cells that are lost to Parkinson’s.

Their new nanomatrix does not require that stem cells be stimulated with growth factors in order to get them to differentiate into dopamine-producing nerve cells.

Instead, the nanomatrix uses trillions of biocompatible silica “nanozigzag” structures on its surface to stimulate stem cells and promote their differentiation.

“When the neural stem cells come into physical contact with our tailor-made nanozigzag matrix in vitro, the ‘physical massage’ can induce the cells to differentiate rapidly into the desired dopaminergic neurons,” Jeffery Huang Zhifeng, associate professor of the Department of Physics at HKBU, and study co-author, said in a press release.

“A self-organized mini-brain-like structure can be developed in only two weeks with risk of carcinogenesis substantially reduced,” Zhifeng added.

After generating mini-SNLSs using the new nanomatrix, the investigators tested how their functionality and therapeutic potential in a rat model of Parkinson’s.

They transplanted the mini-SNLSs they created into the brain of animals whose severe motor impairments mimicked those of Parkinson’s.

Eight weeks later, all transplanted animals started showing progressive improvements in their motor abilities. After 18 weeks, researchers found that newly differentiated, dopamine-producing nerve cells had started to spread around the transplant site, replacing those cells the animals had lost over the course of the disease.

The study noted that first evidence of improvement was seen at 16 weeks post-transplant in previous stem cell work in Parkinson’s animal models, while “motor symptom amelioration was initiated at a much earlier time point following the transplantation of neurons from the mini‐SNLSs.”

No evidence of cancer or tumor formation was found in any of the animals after the transplant. Rats in this model not given a transplant, and used as controls, never showed any signs of motor improvement.

“The results showed that these mini-brain-like structures exhibited excellent survival and functionality in the brains of rats and resulted in the early and progressive improvement of Parkinson’s disease in rats in vivo. It lays the foundation for research into stem cell therapies that may ultimately cure Parkinson’s disease,” Zhifeng said.

This nanomatrix may be used to differentiate stem cells into other cell types, by altering the stiffness, density, and structure of the nanozigzags on its surface, the team added. And it may aid in treatment development for other incurable disorders, such as Alzheimer’s disease and some types of cancer.