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Adult Progenitor Cells Used To Grow Human Blood Vessels In Mice Print E-mail
Science - Biological Sciences
TS-Si News Service   
Friday, 25 July 2008 17:00
Blood Vessel
TS-Si Biological Sciences
Jerusalem, Israel. At a very early stage of human development, all embryonic cells are identical. Unlike adult cells, embryonic cells are very flexible and carry within them the potential to become any tissue type, whether it...
Rochester, NY, USA. Biologists have known for decades that cells use tiny molecular motors to move chromosomes, mitochondria, and many other organelles within the cell. The accuracy and precision of these motors ensure operat...
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Cambridge, MA, USA. Researchers took an important step in developing clinical strategies to grow tissue. For the first time, they successfully grew functional human blood vessels in mice using cells from adult human donors. Rather than extracting fully developed blood vessels from a patient, doctors could obtain suitable cells from blood or bone marrow.
 
Vascularization is the organic process that results in the formation of new blood vessels. Tissue engineering — growing new organs for later implantation into patients — requires laboratory work at a micro scale — microvascularization — to develop good cell sources. This research could eventually facilitate growing new organs and lead to treatments for acute injuries, wound healing, and heart attack.
 
Engineering Robust and Functional Vascular Networks In Vivo With Human Adult and Cord Blood–Derived Progenitor Cells. Juan M. Melero-Martin, Maria E. De Obaldia, Soo-Young Kang, Zia A. Khan, Lei Yuan, Peter Oettgen, and Joyce Bischoff. Circulation Research 2008 103 194-202. doi: 10.1161 / CIRCRESAHA.108.178590 
 
A stem cell can renew itself; that is, cell division can make more stem cells or the cell can differentiate. In the latter process cells divide and with each cycle evolves more and more into practically any cell in the body.
 
Joyce Bischoff, Ph.D., senior author of the study and associate professor at Harvard Medical School and Children’s Hospital Boston.A progenitor cell is an early descendant of a stem cell. It can differentiate into specific cells, but does not renew. A progenitor cell is more limited in the kinds of cells it can become than a stem cell. In scientific terms, progenitor cells are more differentiated than stem cells. 
 
Joyce Bischoff, Ph.D., senior author of the study and associate professor at Harvard Medical School and Children’s Hospital Boston, led a team with Juan M. Melero-Martin, Ph.D., lead author of the study paper. Their findings appear in Circulation Research, a journal of the American Heart Association (AHA).
 
For thie study, the researchers combined two different types of progenitor cells in a culture dish of nutrients and growth factors, then washed off the nutrients and implanted the cells into mice with weakened immune systems.
 
Once implanted, the progenitor cell mixture grew and differentiated into a small ball of healthy blood vessels.
  • endothelial progenitor cells (EPCs),
    which become cells that line the vessels, and
     
  • mesenchymal progenitor cells (MPCs),
    which differentiate into the cells that surround the lining and provide stability.
They found that a mixture of adult blood- and adult bone marrow-derived progenitor cells or a combination of umbilical cord blood-derived and adult bone marrow-derived cells resulted in the greatest density of new blood vessel formation.
 
The ability to rapidly grow two-layered blood vessels without using embryonic or umbilical cord blood stem cells could skirt many ethical concerns, Bischoff said. It would also solve a persistent problem in treating several medical conditions that result from ischemia — the inability of oxygen-rich blood to reach an organ or tissue — such as heart attacks, wound healing and many acute injuries.
 
Bischoff says “What we are most interested in right now is speeding up the vascularization (the formation of blood vessels)” … “We see very good and extensive vasculature in seven days and we’d like to see that in 24 or 48 hours. If you have an ischemic tissue, it’s dying tissue, so the faster you can establish blood flow the better.”
 
If researchers can develop ways to speed the growth of the vessels, non-surgical cardiac bypass procedures could potentially grow new vessels around those blocked by atherosclerosis.
 
Other study findings include:
  • The cells created a vigorous network of vessels that connected to one another and to the vessels of the host mouse within seven days and continued to transport blood during the four-week study.
     
  • Once combined and implanted, the two progenitor cells arranged themselves into vessels with minimal outside help, i.e., without any genetic alteration or manipulation to improve their growth.

    This is important because many growth-promoting genes are the same genes that become activated in cancer.
     
  • Mixtures of EPCs and MPCs from adult donors were as effective at generating vessels as those made from a mixture of cord blood EPCs and adult bone marrow MPCs.

    That finding increases the likelihood of someday being able to easily find clinically useful amounts of progenitor cells.


The United States Army funded this research.

Co-authors are Juan M. Melero-Martin, Ph.D., lead author; Maria E. De Obaldia, A.B.; Soo-Young Kang, Ph.D.; Zia A. Khan, Ph.D.; Lei Yuan, Ph.D.; Peter Oettgen, M.D.; Joyce Bischoff, Ph.D. Individual author disclosures can be found on the manuscript.

 


Engineering Robust and Functional Vascular Networks In Vivo With Human Adult and Cord Blood–Derived Progenitor Cells. Juan M. Melero-Martin, Maria E. De Obaldia, Soo-Young Kang, Zia A. Khan, Lei Yuan, Peter Oettgen, and Joyce Bischoff. Circulation Research 2008 103 194-202. doi: 10.1161 / CIRCRESAHA.108.178590  [ Download PDF ]

Abstract

The success of therapeutic vascularization and tissue engineering will rely on our ability to create vascular networks using human cells that can be obtained readily, can be expanded safely ex vivo, and can produce robust vasculogenic activity in vivo. Here we describe the formation of functional microvascular beds in immunodeficient mice by coimplantation of human endothelial and mesenchymal progenitor cells isolated from blood and bone marrow. Evaluation of implants after 1 week revealed an extensive network of human blood vessels containing erythrocytes, indicating the rapid formation of functional anastomoses within the host vasculature. The implanted endothelial progenitor cells were restricted to the luminal aspect of the vessels; mesenchymal progenitor cells were adjacent to lumens, confirming their role as perivascular cells. Importantly, the engineered vascular networks remained patent at 4 weeks in vivo. This rapid formation of long-lasting microvascular networks by postnatal progenitor cells obtained from noninvasive sources constitutes an important step forward in the development of clinical strategies for tissue vascularization.

 
vascular networks, endothelial progenitor cells, mesenchymal stem cells, mesenchymal progenitor cells, tissue engineering, regenerative medicine, vasculogenesis, angiogenesis
 
TS-Si News ServiceThe TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. The sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.
 
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Last Updated on Friday, 25 July 2008 18:20