Putting Stem Cell Research On The Fast Track

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Putting Stem Cell Research On The Fast Track

http://www.sciencedaily.com/releases/2007/09/070912102212.htm

Engineers at Rensselaer Polytechnic Institute have developed tools

to help solve two of the main problems slowing the progress of stem

cell research -- how to quickly test stem cell response to different

drugs or genes, and how to create a large supply of healthy, viable

stem cells to study from only a few available cells.

The researchers have created methods to study millions of stems

cells on devices the size of a standard microscope slide. The

techniques enable thousands of individual stem cell experiments to

be carried out quickly and in parallel on one small device.

" Rensselaer is quickly establishing itself as leader in the

development of stem cell technology that hastens the speed and

accuracy of stem cell research, " Provost Palazzo said. " Our

scientists and engineers are filling a vital niche in the global

scientific effort to develop medical therapies using stem cells.

Tools like these, which enable high-throughput study of stem cells,

will quickly advance stem cell research in medical labs around the

world. "

The two groups of researchers used microarrays to develop

miniaturized stem cell laboratories. With this technique researchers

can perform high-throughput analysis of the material or cells on a

single slide, analyzing tens of thousands of samples in one

experiment. Each of the teams developed separate specialized

microarray platforms.

Helping develop stem cell drugs

A team led by Dordick, the P. Isermann Professor of

Chemical and Biological Engineering, and visiting doctoral student

Tiago Fernandez and Professor Joaquim M.S. Cabral from the Instituto

Superior Téchinco-Lisbon in Portugal developed a platform that will

enhance the speed of drug discovery by revealing how different

molecules help or hinder stem cell function.

The platform will serve as a tool in the discovery of new drugs that

target stem cells, Dordick said. He explained that although this

three-dimensional system can be used to discover materials that

support stem cell development and growth, not all stem cells are

worth saving. " New research is showing that some stem cells could be

the precursor for cancer and the reason that cancer reappears after

having been totally eradicated by chemotherapy, " he said. " With this

platform we may be able to rapidly screen new drug candidates that

target and kill these stem cells. Instead of going for the mature

liver cell that spreads cancer, we can catch a liver stem cell

before it can kick off cancer development. "

The device will enable drug researchers to quickly screen thousands

of small molecules (the basic element of many modern drugs) for

their impacts on the fate of stem cells.

Dordick's group was able to prepare up to 1,000 drops as small as 20

nanoliters on a chemically modified slide. The drops contained a

mixture of mouse embryonic stem cells encased in a specialized gel.

The researchers discovered that in this mixture, the cells remained

viable and could be used in various forms of cell-based screening.

Their research was presented at the 234th American Chemical Society

National Meeting in Boston on Aug. 19.

Helping understand gene function in stem cells

A separate team led by Professor of Chemical and Biological

Engineering Ravi Kane and Rensselaer doctoral student Randolph

Ashton created a platform that will allow researchers to quickly

understand how different genes impact stem cell function or

development.

" There are millions of DNA bases and tens of thousands of genes

within the human genome, " Kane said. " In order to screen how all

these different DNA sequences affect stem cell function you need an

extremely high throughput method. "

In order to become a specialized organ, tissue, or neural cell, a

stem cell needs to be pointed in the right direction, and that

guidance is believed to be provided by a highly complex arrangement

of genes. If researchers can isolate the specific genetic sequences

that cause a stem cell to transform into a neural cell, the example

that Kane used in his research, they can begin to develop medical

treatments for common diseases like Parkinson's disease using

specially programmed stem cells infected with the correct

arrangement of genes to produce healthy neural cells.

Kane and his team developed a specialized stamping technique that

can be used to quickly understand how different genetic sequences

affect stem cell development. The stamp is covered with thousands of

mircoscale prongs, similar to the surface of a LEGO®. Those prongs

imprint the surface of the corresponding slide, creating a

microarray platform with thousands of individual cell-adhesive

divots -- the perfect mircoscale Petri dishes. The master stamp can

create thousands of stamped surfaces without the needs for a clean

room or sophisticated machinery.

To develop the stem cell mixture added to the stamped surface, the

researchers first created a stem cell library. Each stem cell within

this library would overexpress a different genetic sequence. Cells

from the library are then dropped onto the micropatterned surface,

such that each divot contains only one type of cell. Those seeded

populations then divide to form individual clonal populations of

cells. A stamped surface the size of a microscope slide can contain

3,500 clonal cell populations.

These populations can then be screened at the same time for

researchers to determine which cells exhibit a desired behavior

(i.e. the development of healthy neural cells). The researcher then

immediately knows what DNA sequence is responsible for the observed

behavior.

To exhibit the effectiveness of their technology, Kane and his group

screened clonal populations of rat neural stem cells to identify a

sequence that promoted neural stem cell proliferation.

Their research will be published in upcoming edition of the journal

Stem Cells.

Dordick and Fernandez were assisted in their research by Seok Joon

Kwon, Moo-Yeal Lee, M. Diogo, and Lobata de Silva.

Kane and Ashton were assisted by ph Peltier, Analeah O'Neill,

Leonard, and Schaffer of the University of California

at Berkley and Fasano and Sally Temple of Albany Medical

College.