A team of scientists based in Korea and Canada who transplanted human neural stem cells (hNSCs) into the brains of nonhuman primates (NHPs) report that the hNSCs had differentiated into neurons at 24 months and did not cause tumors. The study is scheduled to be published in Cell Transplantation.
The hNSCs were labeled with magnetic nanoparticles to enable them to be followed by magnetic resonance imaging. The researchers, who did not use immunosuppressants, claim their study is the first to evaluate and show the long-term survival and differentiation of hNSCs without the need for immunosuppression.
“None of the grafted hNSCs were bromodeoxyuridine (BrdU)-positive in the monkey brain indicating that hNSCs did not replicate in the NHP brain and did not cause tumor-formation,” write the investigators in an unedited, available-online copy of the manuscript. “This study serves as a proof-of-principle study to provide evidence that human NSCs transplanted in NHP brain could survive and differentiate into neurons in the absence of immunosuppression, and also serves as a preliminary study in our scheduled preclinical studies of human NSC transplantation in NHP stroke models.”
The researchers maintain that hNSCs could be a key a source for cell replacement and gene transfer for the treatment of Parkinson's disease, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, spinal cord injury, and stroke.
“Stroke is the fourth major cause of death in the U.S. behind heart failure, cancer, and lower respiratory disease,” said study co-author Seung U. Kim, Ph.D., of the University of British Columbia Hospital’s department of neurology. “While tissue plasminogen activator (tPA) treatment within three hours after a stroke has shown good outcomes, stem cell therapy has the potential to address the treatment needs of those stroke patients for whom tPA treatment was unavailable or did not help.”
Dr. Kim and colleagues injected hNSCs into the frontal lobe and the putamen of the monkey brain because they are included in the middle cerebral artery (MCA) territory, which is the main target in the development of the ischemic lesion in animal stroke models. “Thus, research on survival and differentiation of hNSCs in the MCA territory should provide more meaningful information to cell transplantation in the MCA occlusion stroke model,” he explained.
The researchers said that they chose NSCs for transplantation because the existence of multipotent NSCs “has been known in developing rodents and in the human brain with the properties of indefinite growth and multipotent potential to differentiate” into the three major CNS cell types (neurons, astrocytes, and oligodendrocytes).