Featured Research

from universities, journals, and other organizations

Engineered, drug-secreting blood vessels reverse anemia in mice

Date:
November 16, 2011
Source:
Children's Hospital Boston
Summary:
Patients who rely on recombinant, protein-based drugs must often endure frequent injections, often several times a week, or intravenous therapy. Researchers have demonstrated the possibility that blood vessels, made from genetically engineered cells, could secrete the drug on demand directly into the bloodstream. In a new study, they provide proof-of-concept, reversing anemia in mice with engineered vessels secreting erythropoietin (EPO).

Patients who rely on recombinant, protein-based drugs must often endure frequent injections, often several times a week, or intravenous therapy. Researchers at Children's Hospital Boston demonstrate the possibility that blood vessels, made from genetically engineered cells, could secrete the drug on demand directly into the bloodstream. In the Nov. 17 issue of the journal Blood, they provide proof-of-concept, reversing anemia in mice with engineered vessels secreting erythropoietin (EPO).

The technology could potentially be used to deliver other proteins such as Factor VIII and Factor IX for patients with hemophilia, alpha interferon for hepatitis C and interferon beta for multiple sclerosis, says the study's principal investigator, Juan Melero-Martin, PhD, of the Department of Cardiac Surgery at Children's.

Such drugs are currently made in bioreactors by engineered cells, and are very expensive to make in large amounts. "The paradigm shift here is, 'why don't we instruct your own cells to be the factory?'" says Melero-Martin, also an assistant professor at Harvard Medical School.

The researchers created the drug-secreting vessels by isolating endothelial colony-forming cells from human blood and inserting a gene instructing the cells to produce EPO. They then added mesenchymal stem cells, suspended the cells in a gel, and injected this mixture into the mice, just under the skin. The cells spontaneously formed networks of blood vessels, lined with the engineered endothelial cells. Within a week, the vessels hooked up with the animals' own vessels, releasing EPO into the bloodstream.

Tests showed that the drug circulated throughout the body and reversed anemia in the mice, both induced by radiation (as often occurs in cancer patients) and by loss of kidney tissue (modeling chronic kidney failure). Mice with the vessel implants had significantly higher hematocrits (a measure of red blood cell concentration) and recovered from anemia more quickly than controls.

The system also had a built-in on/off control: the inserted EPO-encoding gene was linked to a repressor protein that prevented it from being turned on unless the mice were given the oral drug doxycycline (added to their drinking water). Doxycycline disabled the repressor protein, allowing EPO to be made. When doxycycline was added to the water on a weekly on/off schedule, the animals' hematocrit fluctuated accordingly. When hematocrit reached a normal level, the system could be switched off by simply giving them plain water.

Melero-Martin and colleagues are looking at ways to deliver doxycycline through the skin to avoid exposing the whole body to an antibiotic. There are also other ways to design the genetic on/off control, using synthetic systems or even regulatory elements used naturally by the body -- sensing blood oxygen levels and stimulating EPO production when oxygen levels dip.

A traditional barrier to gene therapy has been getting the genetically altered cells to engraft and stay in place. Blood-vessel implants are an ideal platform technology for gene therapy applications whose goal is systemic drug delivery, says Melero-Martin.

"Blood vessels are one of the few tissues where we have good control over engraftment," he says. "Endothelial cells are easily isolated from blood, are good at assembling themselves into blood vessels, and are ideal for releasing compounds into the bloodstream, since they line the blood vessels."

The lab is interested in trying this system with other therapeutic proteins, and is also exploring ways to get cells to release therapeutics at a moment's notice by getting accumulating stores in advance that could be released upon the proper signal, as beta cells in the pancreas do with insulin, for example.

In addition, Melero-Martin wants to explore regenerative medicine applications, creating blood vessels with genetic instructions to produce factors that attract stem cells or induce cells to differentiate.

The study was funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the National Institutes of Health and the Children's Hospital Boston Department of Cardiac Surgery. Ruei-Zeng Lin, PhD, a research fellow in the Department of Cardiac Surgery at Children's, was first author on the paper.


Story Source:

The above story is based on materials provided by Children's Hospital Boston. Note: Materials may be edited for content and length.


Journal Reference:

  1. R.-Z. Lin, A. Dreyzin, K. Aamodt, D. Li, S.-C. S. Jaminet, A. C. Dudley, J. M. Melero-Martin. Induction of erythropoiesis using human vascular networks genetically-engineered for controlled erythropoietin release. Blood, 2011; DOI: 10.1182/blood-2011-08-372946

Cite This Page:

Children's Hospital Boston. "Engineered, drug-secreting blood vessels reverse anemia in mice." ScienceDaily. ScienceDaily, 16 November 2011. <www.sciencedaily.com/releases/2011/11/111115180317.htm>.
Children's Hospital Boston. (2011, November 16). Engineered, drug-secreting blood vessels reverse anemia in mice. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2011/11/111115180317.htm
Children's Hospital Boston. "Engineered, drug-secreting blood vessels reverse anemia in mice." ScienceDaily. www.sciencedaily.com/releases/2011/11/111115180317.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
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:
from the past week

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