A 'stitch in time' could help damaged hearts

December 09, 2010

WORCESTER, Mass. - A research team at Worcester Polytechnic Institute (WPI) has demonstrated the feasibility of a novel technology that a surgeon could use to deliver stem cells to targeted areas of the body to repair diseased or damaged tissue, including cardiac muscle damaged by a heart attack. The technique involves bundling biopolymer microthreads into biological sutures and seeding the sutures with stem cells. The team has shown that the adult bone-marrow-derived stem cells will multiply while attached to the threads and retain their ability to differentiate and grow into other cell types.

The results are reported in the paper "Fibrin microthreads support mesenchymal stem cell growth while maintaining differentiation potential," which was published online, ahead of print, on Nov. 29, 2010, by the Journal of Biomedical Materials Research (http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.32978/abstract).

"We're pleased with the progress of this work," said Glenn Gaudette, assistant professor of biomedical engineering at WPI and lead author on the paper. "This technology is developing into a potentially powerful system for delivering therapeutic cells right to where they are needed, whether that's a damaged heart or other tissues."

Gaudette's lab is focused on cardiac function, exploring ways to heal damaged heart muscle and to develop cell-based methods to treat cardiac arrhythmias. Much of this work uses human mesenchymal stem cells (hMSCs), which come from the bone marrow and can grow into a range of other tissues in the body, including muscle, bone, and fat. Studies by Gaudette and others have shown that when hMSCs are delivered to damaged hearts, they moderately improve cardiac function. A major challenge in these studies, however, is getting sufficient numbers of the hMSCs to engraft into the damaged heart tissue. Prior methods of injecting the cells into the bloodstream, or directly into the heart muscle, have yielded low results, with 15 percent or less of the cells injected actually surviving and attaching to the heart muscle. Most of the hMSCs delivered by injection are washed away by the bloodstream.

To address the delivery problem, Gaudette teamed up with colleague George Pins, associate professor of biomedical engineering at WPI, who has developed the biopolymer microthread technology as a scaffold or a temporary structure to use in various applications of wound-healing and cellular therapy. The microthreads, which are about the thickness of a human hair, are made of fibrin, a protein that helps blood clot. The threads can be engineered to have different tensile strengths and to dissolve at different rates once implanted so they can be fine-tuned for a variety of uses. Pins is exploring the use of threads to produce replacement tendons and ligaments. Ray Page, assistant professor of biomedical engineering at WPI, leads a team using the microthreads as a platform for fibroblasts to induce skeletal muscle regeneration.

In the current study, Gaudette's team developed protocols to seed hMSCs on small bundles of the fibrin microthreads. Once the stem cells attached to the threads, they were cultured for five days and the data showed the cells began to multiply until the two-centimeter-long threads were virtually covered, with nearly 10,000 cells hMSCs on each ones. After the seeding and growing process, Gaudette's team attached the microthreads to a surgical needle and drew them through a collagen gel made to simulate human tissue. When the threads were drawn through the gel, the vast majority of the stem cells remained alive and attached to threads, suggesting they could be sutured into human tissue.

Gaudette's team also examined the hMSCs that had grown on the threads to see if they remained multipotent, meaning they retain the ability to grow into other types of cells. They removed the hMSCs from the threads and cultured them via established protocols known to prompt hMSCs to differentiate into fat cells and bones cells. In both cases, the cells taken from the microthreads began to differentiate along the pathways that lead to fat and bone tissue. "It appears that the cells we grew on the threads behave the same way we would expect mesenchymal stem cells would in vivo," Gaudette said. "So we believe these results are proof-of-principle--that we can now deliver these cells anywhere a surgeon can place a suture. That's exciting."

Gaudette's team is already at work on the next steps in this line of research, testing the stem cell-seeded microthreads in a rat model to see if they can engraft into heart tissue and improve cardiac function.
-end-
The research reported in the current study was funded by the National Institutes of Health.

About Worcester Polytechnic Institute

Founded in 1865 in Worcester, Mass., WPI was one of the nation's first engineering and technology universities. WPI's14 academic departments offer more than 50 undergraduate and graduate degree programs in science, engineering, technology, management, the social sciences, and the humanities and arts, leading to bachelor's, master's and PhD degrees. WPI's world-class faculty work with students in a number of cutting-edge research areas, leading to breakthroughs and innovations in such fields as biotechnology, fuel cells, information security, materials processing, and nanotechnology. Students also have the opportunity to make a difference to communities and organizations around the world through the university's innovative Global Perspective Program. There are more than 20 WPI project centers throughout North America and Central America, Africa, Australia, Asia, and Europe.

Worcester Polytechnic Institute

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.