Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stowers scientists successfully expand bone marrow-derived stem cells in culture

15.09.2011
All stem cells—regardless of their source—share the remarkable capability to replenish themselves by undergoing self-renewal. Yet, so far, efforts to grow and expand scarce hematopoietic (or blood-forming) stem cells in culture for therapeutic applications have been met with limited success.

Now, researchers at the Stowers Institute for Medical Research teased apart the molecular mechanisms enabling stem cell renewal in hematopoietic stem cells isolated from mice and successfully applied their insight to expand cultured hematopoietic stem cells a hundredfold.

Their findings, which will be published in the Sept. 15, 2011, edition of Genes & Development, demonstrate that self-renewal requires three complementary events: proliferation, active suppression of differentiation and programmed cell death during proliferation.

"The previous efforts so far to grow and expand scarce hematopoietic stem cells in culture for therapeutic applications have been met with limited success", says Stowers investigator Linheng Li, Ph.D., who led the study. "Being able to tap into stem cell's inherent potential for self-renewal could turn limited sources of hematopoietic stem cells such as umbilical cord blood into more widely available resources for hematopoietic stem cells," he adds while cautioning that their findings have yet to be replicated in human cells.

The transplantation of human hematopoietic stem cells isolated from bone marrow is used in the treatment of anemia, immune deficiencies and other diseases, including cancer. However, since bone marrow transplants require a suitable donor-recipient tissue match, the number of potential donors is limited.

Hematopoietic stem cells isolated from umbilical cord blood could be a good alternative source: Readily available and immunologically immature, they allow the donor-recipient match to be less than perfect without the risk of immune rejection of the transplant. Unfortunately, their therapeutic use is limited since umbilical cord blood contains only a small number of stem cells.

Although self-renewal is typically considered a single trait of stem cells, Li and his team wondered whether it could be pulled apart into three distinct requirements: proliferation, maintenance of the undifferentiated state, and the suppression of programmed cell death or apoptosis. "The default state of stem cells is to differentiate into a specialized cell types," explains postdoctoral researcher and first author John Perry, Ph.D. "Differentiation must be blocked in order for stem cells to undergo self-renewal."

Proliferation of stem cells in an undifferentiated state, however, calls tumor suppressor genes into action. These genes help prevent cancer by inducing a process of cell death known as apoptosis. "Consequently, self-renewal of adult stem cells must also include a third event, the active suppression of apoptosis," says Perry.

To test their hypothesis, Perry and his colleagues isolated hematopoietic stem cells from mice and analyzed two key genetic pathways—the Wnt/â-catenin and PI3K/Akt pathways. Wnt proteins had been identified as "self-renewal factors," while PI3K/Akt activation had been shown to induce proliferation and promote survival by inhibiting apoptosis.

Surprisingly, activation of the Wnt/â-catenin pathway alone blocked differentiation but eventually resulted in cell death, while activation of the PI3K/Akt pathway alone increased differentiation but facilitated cell survival. Only when both pathways were activated, did the pool of hematopoietic stem cells start expanding. "This demonstrated both pathways had to cooperate to promote self-renewal," says Perry.

Although altering both pathways drives self-renewal of hematopoietic stem cells, it also permanently blocks their ability to mature into fully functional blood cells. To sidestep the differentiation block and generate normal, functioning hematopoietic stem cells usable for therapy, the Stowers scientists used small molecules to reversibly activate both the Wnt/â-catenin and PI3K/Akt pathways in culture.

"We were able to expand the most primitive hematopoietic stem cells, which, when transplanted back into mice gave rise to all blood cell types throughout three, sequential transplantation experiments," says Li. "If similar results can be achieved using human hematopoietic stem cells from sources such as umbilical cord blood, this work is expected to have substantial clinical impact."

Researchers who also contributed to the work include Xi C. He, Ryohichi Sugimura, Justin C. Grindley and Jeffrey S. Haug at the Stowers Institute for Medical Research and Sheng Ding in the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco.

The work was funded in part by the Stowers Institute for Medical Research and the Leukemia & Lymphoma Society.

About the Stowers Institute for Medical Research

The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife Virginia opened the Institute in 2000. Since then, the Institute has spent over 800 million dollars in pursuit of its mission. Currently the Institute is home to nearly 500 researchers and support personnel; over 20 independent research programs; and more than a dozen technology development and core facilities. Learn more about the Institute at www.stowers.org.

Gina Kirchweger | EurekAlert!
Further information:
http://www.stowers.org

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>