Researchers have successfully generated stable lines of spinal cord neural stem cells (NSCs), which, when transplanted into a rat model of spinal cord injury, were able to become multiple types of neurons and drive spine regeneration.
Derived from human embryonic stem cells (hESCs), these induced cells also included progenitors that give rise to motor neurons, those that are gradually lost throughout the course of spinal muscular atrophy (SMA).
NSCs are able to grow into any type of nerve cell, while hESCs are derived from pre-implantation embryos that are able to give rise to any type of cell in the body, while maintaining a “self-renewal” capability, meaning their ability to divide and generate identical “daughter” stem cells.
Conducted by researchers at the University of California in San Diego and funded partly by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), findings were published in the study, “Generation and post-injury integration of human spinal cord neural stem cells,” in the journal Nature Methods.
“Scientists have been very enthusiastic about the potential to use neural stem cells to treat a number of spinal cord disorders including spinal cord injury, amyotrophic lateral sclerosis [ALS], and spinal muscular atrophy,” Rosemarie Hunziker, PhD, director of the NIBIB Tissue Regeneration Program, said in a press release. “A real bottleneck in bringing this innovation to patients, however, is the ability to control the cell’s identity as a particular functional nerve cell, while preserving its ability to proliferate and provide a large number of these cells.”
When cultured in vitro, NSCs have a tendency to grow into different types of nerve cells and gradually lose their ability to grow, which does pose a serious limitation in the amount of undifferentiated NSCs researchers are able to harvest for transplantation.
Now, a team of investigators, led by Mark H. Tuszynski, MD, PhD, from the Center for Neural Repair at the University of California, may have found a workaround to this problem by creating a process based on the use of hESCs to generate large numbers of undifferentiated NSCs in a lab culture dish.
“With the ability to expand and maintain large numbers of undifferentiated neural stem cells, we believe that advancement to human clinical trials could be in a time frame of as little as five years,” said first author Hiromi Kumamaru, MD, PhD. “However, the safety and efficacy of the cells will first have to be established in additional studies in rats and non-human primates.”
The strategy involves providing hESCs with a cocktail of proteins that simultaneously stimulate the growth of undifferentiated NSCs, while preventing their differentiation into other cell types. Using this approach, NSCs were able to retain their ability to differentiate and give rise to multiple types of nerve cells when transplanted to spinal cord injury sites in a rat model of disease.
The NSCs regenerated extensive regions of the spinal cord and large numbers of functional axons (the long thread-like part of a nerve cell) that extended over long distances to innervate their target tissues.
“These NSCs include all spinal cord NPC [neural progenitor cells] types and can yield a broad range of identified spinal cord [neurons] together with … glial cell types [nerve cells that support neurons]. Our hESC-derived NSCs could, [therefore], constitute the optimal cell type for clinical translation for spinal cord ‘replacement’strategies in SCI [spinal cord injury] or other disorders,” the investigators wrote.
Besides their promising use for transplantation therapy, NSCs may be equally valuable as an in vitro tool to “facilitate disease modeling and drug screening for several spinal cord disorders,” including amyotrophic lateral sclerosis (ALS), SMA, and progressive muscular atrophies, according to the researchers.
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