iPS-Derived Microglia-Based Gene Therapy for Alzheimer's
Extracting bone marrow cells requires surgery, which may be strenuous or impossible for older patients. To meet large scale demand of bone marrow cells in the clinic for the treatment of Alzheimer's disease, the team will generate bone marrow cells from blood, which will in turn be genetically modified to secrete drugs once these cells migrate to the brain.
To make bone marrow cells from blood, Dr. Chandu’s team first collected blood and then isolated white blood cells. These white blood cells were cultured in dishes using specialized incubators for tissue culture. The cells were then "forced" to express certain stem cell-associated genes by a gene therapy technique. After 3-4 weeks, small numbers of the genetically-altered cells became similar to embryonic stem cell-like cells called induced pluripotent stem cells (iPSC). These iPSC will later be converted to bone marrow cells under specific cell culture conditions. The team was able to convert the blood cells to embryonic stem cell-like cells, but they didn’t survive, perhaps because the blood cells were not completely converted. Currently, Dr. Chandu’s team is fine-tuning the culture conditions for conversion to iPSC. Once successful, the team will continue their plan to deliver the drug-expressing cells into mice with Alzheimer’s disease.
About the Researcher
Dr. Biju Chandu is a postdoctoral fellow in the Department of Medicine at the University of Texas Health Science Center in San Antonio, Texas. He completed his doctoral studies in Neuroscience at the Department of Pharmaceutical Sciences, Nagpur University, India. In 2004 he moved to the Neuroscience Program at Florida State University to do postdoctoral work with Prof. Debra Fadool. Some of his experiments with Prof. Fadool drew his attention to that fact that increasing the levels of certain neurotrophic factors might provide great benefit to people suffering from neurodegenerative diseases. To learn more about the impact neurotrophic factors might have on reversing the course of neurodegenerative diseases, he moved to the laboratory of Dr. Senlin Li at the University of Texas Health Science Center. At the Health Science Center Chandu has been collaborating with Dr. Li to develop and test neuroprotective therapeutics for neurodegenerative diseases.
Currently, they use bone marrow-derived macrophages as a cellular vehicle to deliver neurotrophic factors to the degenerating neurons. The use of macrophages to deliver neurotrophic factors is particularly attractive, given that these cells are capable of crossing the blood-brain barrier, after which they differentiate into microglia and are preferentially recruited in large numbers to sites of neurodegeneration. They are also performing experiments to determine whether different kinds of neurotrophic factors have more and less beneficial effects. Extracting bone marrow requires surgery, which may be strenuous or impossible for older patients. To address the issue, they have begun working on generating macrophages using induced pluripotent stem cell technology.
First published on: July 6, 2011
Last modified on: March 18, 2013