Posted by Victoria Stern 5th October 2009, "The Scientist.com"
Nanoparticles may prove effective tools for improving stem cells therapy, new research suggests. Chemical engineers have successfully used nanoparticles to enhance stem cells' ability to stimulate regeneration of damaged vascular tissue and reduce muscle degeneration in mice, they report in a study published online today (October 5) in Proceedings of the National Academy of Sciences.
"This is an intriguing finding," said Arnold Kriegstein, a regenerative biologist at the University of California, San Francisco, who was not involved in the study. "But it would need to be explored a good deal further before one could really be excited about this new approach."
Researchers studying the role of stem cells in stimulating new blood vessel formation have suggested that after implantation into a living organism, cells may not continue to renew tissue effectively enough to keep the tissue alive long-term. The cells can therefore benefit from help with performance-enhancing genes, which promote growth in the target tissue. Researchers generally rely on viral vectors to deliver these therapeutic genes to stem cells. "We hypothesized that with the right DNA delivery system, we could [better] enhance the therapeutic utility of stem cells," said Daniel Anderson of the Massachusetts Institute of Technology, lead author on the study.
Anderson and his team cultured stem cells from mouse bone marrow and then introduced nanoparticles containing positively charged polymers that can bind to and deliver DNA to cells to the culture medium. Specifically, the nanoparticles carried the gene for vascular endothelial growth factor (VEGF), a signaling molecule known to stimulate the growth of new blood vessels. The modified stem cells containing the DNA were then implanted into eight mice in areas with damaged tissue. The researchers believe that cells engulf the gene-carrying nanoparticles with their cell membrane and the molecules release DNA inside the cell, Anderson said in an email, though he noted that "[t]he precise mechanism by which these [nanoparticles] deliver DNA is not clear yet."
The MIT researchers found that after two weeks, the cells transfected with VEGF had two to four times more blood vessel density around the damaged tissue than cells without the gene or cells that received the gene using a common delivery molecule. Four weeks after injection, the modified stem cells continued to boost the growth of new blood vessels while reducing muscle degeneration in the mice.
"We think it's an important demonstration that biodegradable polymers can be used to temporarily modify stem cells and enhance their therapeutic performance," Anderson wrote in an email.
Kriegtein said, however, that he worries the reported benefits using nanoparticles may be transient. In the study results, he noted, there was a significant increase in VEGF levels in mouse muscle two days following cell grafting, but VEGF levels produced by the cells dropped sharply after four days.
Kriegstein suggested that using an adenoviral vector to deliver the growth gene would make more sense than using nanoparticles. Though there have been some safety concerns, he said, studies have shown the viral vector approach can last longer and produces greater gene activity than the nanoparticle method.
Although the study authors acknowledge the advantages of a viral delivery method, they believe that using nanoparticles is much safer than a viral vector and, with more tweaking, has great potential for long-term therapeutic benefits for stem cell therapy, Anderson said.
Looking forward, "I think these nanoparticles will be useful not just to modify stem cells, but also to treat cancers and genetic diseases," Anderson said.
Nanoparticles may prove effective tools for improving stem cells therapy, new research suggests. Chemical engineers have successfully used nanoparticles to enhance stem cells' ability to stimulate regeneration of damaged vascular tissue and reduce muscle degeneration in mice, they report in a study published online today (October 5) in Proceedings of the National Academy of Sciences.
"This is an intriguing finding," said Arnold Kriegstein, a regenerative biologist at the University of California, San Francisco, who was not involved in the study. "But it would need to be explored a good deal further before one could really be excited about this new approach."
Researchers studying the role of stem cells in stimulating new blood vessel formation have suggested that after implantation into a living organism, cells may not continue to renew tissue effectively enough to keep the tissue alive long-term. The cells can therefore benefit from help with performance-enhancing genes, which promote growth in the target tissue. Researchers generally rely on viral vectors to deliver these therapeutic genes to stem cells. "We hypothesized that with the right DNA delivery system, we could [better] enhance the therapeutic utility of stem cells," said Daniel Anderson of the Massachusetts Institute of Technology, lead author on the study.
Anderson and his team cultured stem cells from mouse bone marrow and then introduced nanoparticles containing positively charged polymers that can bind to and deliver DNA to cells to the culture medium. Specifically, the nanoparticles carried the gene for vascular endothelial growth factor (VEGF), a signaling molecule known to stimulate the growth of new blood vessels. The modified stem cells containing the DNA were then implanted into eight mice in areas with damaged tissue. The researchers believe that cells engulf the gene-carrying nanoparticles with their cell membrane and the molecules release DNA inside the cell, Anderson said in an email, though he noted that "[t]he precise mechanism by which these [nanoparticles] deliver DNA is not clear yet."
The MIT researchers found that after two weeks, the cells transfected with VEGF had two to four times more blood vessel density around the damaged tissue than cells without the gene or cells that received the gene using a common delivery molecule. Four weeks after injection, the modified stem cells continued to boost the growth of new blood vessels while reducing muscle degeneration in the mice.
"We think it's an important demonstration that biodegradable polymers can be used to temporarily modify stem cells and enhance their therapeutic performance," Anderson wrote in an email.
Kriegtein said, however, that he worries the reported benefits using nanoparticles may be transient. In the study results, he noted, there was a significant increase in VEGF levels in mouse muscle two days following cell grafting, but VEGF levels produced by the cells dropped sharply after four days.
Kriegstein suggested that using an adenoviral vector to deliver the growth gene would make more sense than using nanoparticles. Though there have been some safety concerns, he said, studies have shown the viral vector approach can last longer and produces greater gene activity than the nanoparticle method.
Although the study authors acknowledge the advantages of a viral delivery method, they believe that using nanoparticles is much safer than a viral vector and, with more tweaking, has great potential for long-term therapeutic benefits for stem cell therapy, Anderson said.
Looking forward, "I think these nanoparticles will be useful not just to modify stem cells, but also to treat cancers and genetic diseases," Anderson said.