BOSTON — Invitrogen last week said that researchers at the Burnham Institute are using its NCode miRNA arrays to study embryonic stem cells.
The company also said that it has abandoned a similar deal with Johns Hopkins University because of restrictions placed on the kinds of embryonic stem cell lines that can be used outside of California.
Invitrogen also has embryonic stem cell collaborations with Rutgers University and American Type Culture Collection.
Christopher Adams, a research area manager in Invitrogen's life sciences division, said that Mark Mercola's lab at the Burnham Institute is studying the therapeutic use of cardiomyocytes. He said the lab has been exploring ways to more easily culture the cells, and has been working with Invitrogen to use miRNAs to control embryonic stem-cell differentiation.
"The main direction we are going in is to see if miRNA regulation can be manipulated to control stem-cell differentiation," Adams said during a presentation at Cambridge Healthtech Institute's Microarrays in Medicine conference, held here last week.
"Clearly the whole idea of being able to dictate cell fate is a very intriguing possibility for people who work in the stem cell field," he told BioArray News after his talk. "That promise is why stem cell researchers seem to be really focused on miRNAs and their role right now."
According to Adams, Mercola’s lab is interested mainly in therapeutic applications. “Evidently, there's some data showing that you can actually inject cardiomyocytes into damaged heart tissue and regenerate heart tissue,” he said. “So there's a lot of potential there [for] a stem-cell therapeutic for heart attack patients and things like that where you have dead heart tissue as a result of ischemia.”
He said that the biggest hurdle for that therapeutic application is being able to culture enough cardiomyocytes to be able to have any therapeutic value. "You need a critical mass of these cells for it to have any positive effect," Adams said. He also said that once cultured, cardiomyocytes are difficult to replicate.
"So you can't make tons of these cells, and we want to both be able to trigger differentiation in a much easier way than what they are currently doing and also so that they'll be able to stimulate replication so that you can very quickly and easily grow up large populations," said Adams.
"The idea is that we will identify some interesting microRNAs that may be involved in that differentiation process and then make some of the over-expression knockdown tools,” Adams said. Invitrogen will then give the information Mercola and in his lab “he would then investigate the role of these microRNAs and see if it is possible to more easily stimulate cardiomyocyte differentiation," he added.
Mark Mercola did not return a phone call and an e-mail seeking comment.
JHU Falls Through; Others Move Ahead
Adams also said that Invitrogen had a similar stem cell research collaboration with John Hopkins University, although he declined to discuss the nature of that research. However, Adams and Amy Butler, Invitrogen's vice president of gene-expression profiling, told BioArray News in an e-mail this week that the company has ended the JHU collaboration.
"We decided not to move forward with the collaboration with Johns Hopkins due to restrictions on the use of some of the selected embryonic stem cell lines," they wrote.
Invitrogen and JHU have close ties. For example, Mahendra Rao, a former professor at JHU, joined Invitrogen as vice president of stem cell and regenerative medicine research last year (see BAN 4/18/2006).
Calls and e-mails to JHU were not returned.
Other academic and industrial collaborators have used Invitrogen's NCode platform in embryonic stem cell research. Butler and Adams pointed out that Invitrogen has been collaborating with Ron Hart, a professor of cell biology and neuroscience at Rutgers University, who "explored the correlation of miRNA expression and potential mRNA targets."
Invitrogen has also worked with ATCC researchers Jonathan Auerbach and Richard Josephson to study miRNA expression of embryonic stem cells, Butler and Adams wrote. Their study was published in the February issue of Stem Cells. [Josephson et al. Qualification of embryonal carcinoma 2102Ep as a reference for human embryonic stem cell research. Stem Cells. 2007 Feb;25(2):437-46.].
"Clearly the whole idea of being able to dictate cell fate is a very intriguing possibility for people who work in the stem cell field."
“I see [miRNA expression] as analogous to gene expression,” said lead author Richard Josephson, a former research scientist at ATCC who has since left to join the firm Global Stem as a senior scientist.
“You can track differentially expressed miRNAs in embryonic stem cells — that’s how we looked at the data,” he told BioArray News this week.
Adams said in Boston that the reason stem-cell researchers seem to be focused on miRNAs and their role is that, "number one, it's clearly to show that they are intricately involved in differentiation — they control the genetic networks to some degree that are involved in determining cell fate and lineage."
A second reason is that they make excellent markers for different stages of differentiation," he explained. "If you have a population of embryonic stem cells you've been growing in culture, a lot of times they'll just begin to spontaneously differentiate for unknown reasons," he said. "So, the flipside is that not only do you want to be able to stimulate them to go down a certain pathway at will, you also want to be able to keep them from going down any pathway."
“There is some evidence that different human embryonic stem cell lines have different responses to induction,” Josephson said. “It would be very interesting to compare two lines after induction using miRNA arrays,” he said.
Adams said that he could envision Invitrogen creating products that arise from its embryonic stem-cell alliances. "At Invitrogen, we're a big media company and we sell a lot of media for growing stem-cell populations," he said, adding that the company could "come up with some type of media that might have some kind of an miRNA connection so that when you grow your embryonic stem cells in the media, they won't differentiate."
However, while Invitrogen says its embryonic stem cell research will drive sales of its NCode arrays, other miRNA players say that they are pursuing more traditional routes for their chips, such as oncological research.
For example, Steven Kain, Agilent Technologies' genomics section manager, told BioArray News in an e-mail this week that while the company’s newly launched miRNA array is “very well-suited for embryonic stem cell analysis," the company is "pursuing traditional disease research markets first, with embryonic stem cell work to follow."
Agilent became the latest firm to join the miRNA array market this month. Other companies with chips, services, or applications on the market include CombiMatrix, Asuragen, Exiqon, and Febit.