Genetically engineered cells show promise in treating ALS and blinding diseases

summary: Artificial stem cells may lead to personalized treatments for various neurological and visual disorders, a new study reports. Transplantation of induced pluripotent stem cells into the eyes of rodents with retinal degeneration protected the eye cells that support vision. In an ALS model, transplantation of cells into the spinal cord protected the cells that control movement. The engineered cells also created astrocytes and did not lead to tumorigenesis.

sauce: Cedars-Sinai Medical Center

Researchers at Cedars-Sinai are developing new ways to treat amyotrophic lateral sclerosis (ALS) and retinitis pigmentosa using engineered stem cells, ultimately leading to personalized treatments There is a possibility.

This new approach uses renewable and scalable human induced pluripotent stem cell (iPSC)-derived cells and can also slow the progression of these neurodegenerative diseases in rodents.

This study was published in the journal stem cell reportrepresents an important first step toward achieving more individualized treatment for people with these debilitating conditions, for which there is currently no cure.

Dr. Clive Svendsen, Executive Director of Cedars-Sinai, said: Council Institute for Regenerative Medicine and Professor of Biomedical Sciences and Medicine.

The team has previously shown that neural progenitor cells can be engineered to produce a protein called glial cell line-derived neurotrophic factor (GDNF). This protein helps maintain diseased neurons.

This product was safely implanted into the spinal cord of ALS patients in a recently completed trial. With a single treatment, the cells can survive for more than three years, produce an important GDNF protein, and may protect motor neurons that die in ALS. It is also used in degenerative tests.

“But the cell lines we use in our clinic are from a single source and will eventually run out. We don’t have an infinite number of products,” he said. said Svendsen, who is also the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine at Cedars-Sinai.

“Induced pluripotent stem cells provide a renewable source, allowing us to develop more sustainable products that can be engineered to release potent growth factors.”

Scientists are discovering that cell and gene therapies have great potential in treating a variety of diseases, including difficult-to-treat neurodegenerative diseases such as ALS and retinitis pigmentosa.

After transplantation, the stem cells generate support cells that release drugs designed to support degenerating neurons. However, limitations that may hinder the widespread use and commercialization of these therapies include insufficient tissue availability and potential rejection of cells by patients.

Dr. Alexander Laperle, project scientist at the Svendsen Laboratory and co-first author of the study, said:

To test iPSC-based therapies, the team engineered iPSC-derived neural progenitor cells to produce GDNF and see if it could be used to treat diseases that cause death of nervous system cells, such as ALS and retinal degeneration. confirmed.

The researchers found that when these iPSC-derived neural progenitor cells were placed in the eyes of rodents with retinal degeneration, the eye cells that support vision were protected.

When the team transplanted the same cells into the spinal cords of rodents with ALS, they found that the cells helped protect the spinal cord cells that control movement. They also found that it did not cause tumors or other problems when implanted in animals for several months.

Co-first author Alexandra Moser, Ph.D., postdoctoral fellow at the Svendsen Laboratory, said: “They also formed mostly astrocytes, protective and supportive cells, and we found that they continued to produce GDNF. Most importantly, they did not form tumors.”

“We have successfully demonstrated that human iPSCs that stably produce GDNF can be developed as a promising future cell and gene therapy,” said Laperle.

Although the study results showed promise, more preclinical studies are needed to determine the optimal treatment level, Moser said. The team is currently looking into expanding these cells and how to improve the scalability of that process.

About this genetic research news

author: Dennis Headey
sauce: Cedars-Sinai Medical Center
contact: Dennis Headey – Cedars Sinai Medical Center
image: image is public domain

Original research: open access.
“Human iPSC-derived neural progenitor cells secreting GDNF protect rodent models of ALS and retinal degeneration” Clive Svendsen et al. stem cell report

overview

Human iPSC-derived neural progenitor cells secreting GDNF protect rodent models of ALS and retinal degeneration

highlight

• Human iNPC-GDNF differentiate into astrocytes. in vitro and live
• iNPC-GDNF can protect cells and function in diseased rat retinas and spinal cords
• iNPC-GDNF shows long-term survival and GDNF production in nude rat spinal cord
• iNPC-GDNF offers a safe and scalable combined cell and gene therapy

summary

Human induced pluripotent stem cells (iPSCs) are a renewable cell source that can be differentiated into neural progenitor cells (iNPCs) and transduced with glial cell line-derived neurotrophic factor (iNPC-GDNF).

The goal of the current study is to characterize iNPC-GDNF and test its therapeutic potential and safety. Mononuclear RNA-seq shows that iNPC-GDNF expresses her NPC markers. iNPC-GDNF introduced into the subretinal space of the Royal Society of Surgeons rodent model of retinal degeneration preserves photoreceptor and visual function.

Furthermore, iNPC-GDNF transplantation into the spinal cord of SOD1^G93A Amyotrophic lateral sclerosis (ALS) rats preserve motor neurons.

Finally, when iNPC-GDNF is implanted into the spinal cord of athymic nude rats, GDNF survives and is produced for 9 months with no signs of tumorigenesis or continued cell proliferation. iNPC-GDNF is long-lived, safe, and provides neuroprotection in both models of retinal degeneration and ALS, demonstrating its potential as a combination cell-gene therapy for a variety of neurodegenerative diseases.