Featured Research

from universities, journals, and other organizations

Single drug and soft environment can increase platelet production, researchers show

Date:
July 13, 2011
Source:
University of Pennsylvania
Summary:
Humans produce billions of clot-forming platelets every day, but there are times when there aren't enough of them, such as with certain diseases or during invasive surgery. Now, researchers have demonstrated that a single drug can induce bone marrow cells called megakaryocytes to quadruple the number of platelets they produce.

Megakaryocytes in bone marrow.
Credit: Image courtesy of University of Pennsylvania

Humans produce billions of clot-forming platelets every day, but there are times when there aren't enough of them, such as with certain diseases or during invasive surgery. Now, University of Pennsylvania researchers have demonstrated that a single drug can induce bone marrow cells called megakaryocytes to quadruple the number of platelets they produce.

Related Articles


Jae-Won Shin, a graduate student of pharmacology in Penn's Perelman School of Medicine, and Dennis E. Discher, professor in the Department of Chemical and Biomolecular Engineering in the School of Engineering and Applied Science, led the research. They collaborated with Joe Swift and Ph.D. student Kyle R. Spinler, also of Chemical and Biomolecular Engineering.

Their research was published in the journal Proceedings of the National Academy of Sciences.

Megakaryocytes are the large bone marrow cells that produce platelets, the smaller cell fragments that form clots to seal blood vessels when the vessels are damaged. The amount of platelets they produce relates to their size. Unlike most other cells, when megakaryocytes copy their DNA, they don't split into two cells but continue to grow larger.

"These cells take the relatively unusual step of becoming bigger and bigger, adding multiple nuclei, which you don't see with other cell types," Discher said. "Mature, multinucleated megakaryocytes are better than uni- or bi-nucleated ones; they have more mass and are ready to make more platelets."

When mature, the megakaryocyte will extend a tendril into a neighboring blood vessel; the flow of blood pulls off pieces of the cell, forming platelets. The motor protein myosin-II plays a number of roles in this process; by inhibiting it with a drug known as belebbistatin, the researchers caused megakaryocytes to make up to four times as many platelets as when it is active.

Myosin-II is responsible for many body systems that require contractile tension, such as flexing one's muscles. In many cells, it is responsible for the integrity of the outer membranes, for cell division and for key aspects of adhesion. Because megakaryocytes are best when they are large, multi-nucleated and fragment easily, inhibiting myosin-II helps produce more platelets in three distinct ways.

"The first factor is when cells normally divide, there is a contracting force between the dividing cells that cleave them apart," Shin said. "But if you inhibit myosin, there is no contracting force and cells grow without dividing. That's how they become multi-nucleated and how the cell mass becomes bigger.

"The second factor is cytoskeletal stiffness and tension in the cell. When myosin is active, the cell is stiff and tense like well-toned muscle, but if you inhibit the myosin, the cell becomes flaccid and more easy to push around and fragment," he said.

"The third factor is that cells are able to sense the stiffness of their microscopic environment and react to it, which is also regulated by cellular contractivity," Shin said. "Adhering to bone inhibits megakaryocyte growth; without myosin-II, they grow as if they were adhering to something soft."

By testing the megakaryocytes' growth in different cell culture dishes and gels, the researchers were also able to show that a soft matrix, similar to squishy bone marrow, induced more platelet production than a rigid matrix.

After growing the platelets in Petri dishes saturated with the myosin-II inhibitor blebbistatin, the megakaryocytes were soft enough to spontaneously fragment into platelets. Because platelets need functioning myosin-II to form rigid clots, the researchers subsequently washed away the drug to show that the platelets could still activate.

While the researchers also transplanted blebbistatin-treated human megakaryocytes into genetically modified mice to show that they maintained their increased platelet production within living systems, most of their work was done in vitro to demonstrate that platelets could be successfully synthesized in a lab.

"Platelet transfusions are harder and harder to come by. Not only are there contamination issues, but platelets are also very short-lived," Shin said. "They only last about a week in a transfusion bag. The ability to make them in large quantities could save lives."

The research was supported by the National Institutes of Health, the Human Frontier Science Program and the American Heart Association.


Story Source:

The above story is based on materials provided by University of Pennsylvania. Note: Materials may be edited for content and length.


Cite This Page:

University of Pennsylvania. "Single drug and soft environment can increase platelet production, researchers show." ScienceDaily. ScienceDaily, 13 July 2011. <www.sciencedaily.com/releases/2011/07/110713121303.htm>.
University of Pennsylvania. (2011, July 13). Single drug and soft environment can increase platelet production, researchers show. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2011/07/110713121303.htm
University of Pennsylvania. "Single drug and soft environment can increase platelet production, researchers show." ScienceDaily. www.sciencedaily.com/releases/2011/07/110713121303.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins