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BME Ph.D. candidate Ram Rao is one of two recipients of the 2013 RPM Ventures Student Entrepreneur of the Year award! In 2010, Rao co-founded STIgma Free Diagnostics, a medical device company dedicated to developing a rapid at-home test for the detection of common sexually transmitted diseases. Ram is a member of BME Professor Jan Stegemann’s CMITE lab. Congratulations, Ram and keep up the great work!
Read more about the award and Ram here: http://bit.ly/Y8otjF
ANN ARBOR—One of the major obstacles to growing new organs—replacement hearts, lungs and kidneys—is the difficulty researchers face in building blood vessels that keep the tissues alive, but new findings from the University of Michigan could help overcome this roadblock.
“It’s not just enough to make a piece of tissue that functions like your desired target,” said Andrew Putnam, U-M associate professor of biomedical engineering. “If you don’t nourish it with blood by vascularizing it, it’s only going to be as big as the head of a pen.
“But we need a heart that’s this big,” he added, holding up his fist.
More immediately, doctors and researchers believe figuring out how to grow working blood vessels might offer treatments for diseases that affect the circulatory system such as diabetes. Perhaps the right drug or injection could save patients’ feet from amputation.
Putnam and his colleagues have revealed why one of the leading approaches to building blood vessels isn’t consistently working: It’s making leaky tubes. They also demonstrated how adult stem cells could solve this problem. A paper on the findings is published online in Tissue Engineering Part A, and will appear in a forthcoming print edition.
Today, biomedical researchers are taking two main approaches to growing new capillaries, the smallest blood vessels and those responsible for exchanging oxygen, carbon dioxide and nutrients between blood and muscles or organs.
One group of researchers is developing drug compounds that would signal existing vessels to branch into new tributaries. These compounds—generally protein growth factors—mimic how cancerous tumor cells recruit blood vessels.
The other group, which includes the U-M team, is using a cell-based method. This technique involves injecting cells within a scaffolding carrier near the spot where you want new capillaries to materialize. In Putnam’s approach, they deliver endothelial cells, which make up the vessel lining and supporting cells. Their scaffolding carrier is fibrin, a protein in the human body that helps blood clot.
“The cells know what to do,” Putnam said. “You can take these things and mix them and put them in an animal. Literally, it’s as easy as a simple injection and over a few days, they spontaneously form new vessels and the animals’ own vasculature connects to them.”
But it turns out these vessels don’t always thrive. The U-M team aimed to figure out why. In reading previously published findings, Putnam noticed that researchers used “a mishmash of support cells,” and the field had paid little attention to which ones work best. So that’s where he and his colleagues focused.
In their experiments, they mixed three recipes of blood vessel starter solutions, each with a different commonly used supporting cell type: lung fibroblasts, adult stem cells from fat and adult stem cells from bone marrow. They also made a version with no supporting cells at all. They injected each solution under the skin of mice, and allowed the new blood vessels to form over a period of two weeks. At various points in time, they injected a tracer dye into the animals’ circulation to help them see how well the engineered capillaries held blood, and whether they were connected to the animals’ existing vessel networks.
The researchers found that the solution with no support cells and the one with the lung fibroblasts produced immature, misshapen human capillaries that leaked. They could tell because the tracer dye pooled in the tissue around the new vessels. On the other hand, the solutions with both types of adult stem cells gave rise to robust human capillaries that kept blood and dye inside them.
The paper notes that one popular method biomedical engineers use to check the success of their efforts—counting blood vessels—might not be an ideal measure. The adult stem cell solutions produced fewer blood vessels than the others, in one case less than half. But the vessels they did build were stronger. And upon further analysis, the researchers found evidence that the adult stem cells may be able to differentiate into the kind of mature, smooth muscle cells that support larger blood vessels.
“The adult stem cells from fat and bone marrow both work equally well,” Putnam said. “If we want to use this clinically in five to 10 years, I think it’s crucial for the field to focus on a support cell that actually has some stem cell characteristics.”
Down the road, Putnam envisions that doctors could get these support cells from individual patients themselves—either from their bone marrow or fat—and then inject them near the site where the new blood vessels are needed.
The paper is titled, “Stromal Cell Identity Influences the In Vivo Functionality of Engineered Capillary Networks Formed by Co-delivery of Endothelial Cells and Stromal Cells.” The research was funded by the National Institutes of Health (Grant Numbers R01-HL085339 and R01-HL085339-03).
Published on Apr 04, 2013
Contact Nicole Casal Moore
Original U-M News Service article: http://www.ns.umich.edu/new/multimedia/videos/21358-building-better-blood-vessels-could-advance-tissue-engineering
Full text of paper: http://online.liebertpub.com/doi/pdf/10.1089/ten.tea.2012.0281
Andrew Putnam: www.sitemaker.umich.edu/cset/home
Tags: Andrew Putnam, Blood vessels, build blood vessels, cell engineering, College of Engineering, engineering alumni, engineering topics, engineering video, healthcare, mconnex, michepedia, michigan alumni, Michigan Engineering, Professor Putnam, Putnam, replacement organs, Stem Cells, Tissue Engineering, u-m, u-m alumni, UM, University of Michigan, uofm
Posted in All News, Faculty News, Spotlight
Two Biomedical Engineering graduate students were among the the 2013 recipients of the Outstanding Graduate Student Instructor Awards sponsored by the Rackham Graduate School. Sakib Elahi and William Lloyd, both took home the 2013 Outstanding GSI award. Sakib has been the GSI for BME 231, 241, and 458 and Bill was GSI for BME 450, 499, and 241. Sakib and Bill are both members of BME Professor Mary-Ann Mycek’s Biomedical Optics Laser Laboratory. The awards ceremony that will honor these talented teachers will be held on Thursday, April 18, 2013 at 2:00 p.m. in the Rackham Amphitheater with a public reception to follow.
“Nanoparticles, which are popular candidates for ferrying drugs to target locations in the human body, have been shown to evade the immune system and infiltrate tissues and cells. This makes them effective in delivering medication for conditions such as cardiovascular disease and cancer.
But, Michigan Engineering Professor Lola Eniola-Adefeso and her team has discovered they’re no good at leaving the bloodstream, getting trapped instead by red blood cells. To combat that, researchers are exploring the possibility of different shapes for these nanoparticles, to help them more effectively navigate to their targets.”
Professor Lola Eniola-Adefeso, who also holds a joint appointment in the Department of Biomedical Engineering along with her position in Chemical Engineering, is featured in the latest MconneX MichEpedia video. Check it out here!
Tags: arteriosclerosis, biomedical engineering, blood cells, Cancer, cardiovascular disease, Chemical Engineering, College of Engineering, drug carriers, engineering alumni, engineering topics, engineering video, lola eniola-adefeso, mconnex, michepedia, michigan alumni, Michigan Engineering, nano drug carriers, nano engineering, nano spheres, nanoparticles, professor eniola, red blood cells, u-m, u-m alumni, UM, University of Michigan, uofm
Posted in All News, Faculty News, Spotlight
ANN ARBOR—A thin, flexible electrode developed at the University of Michigan is 10 times smaller than the nearest competition and could make long-term measurements of neural activity practical at last.
This kind of technology could eventually be used to send signals to prosthetic limbs, overcoming inflammation larger electrodes cause that damages both the brain and the electrodes.
The main problem that neurons have with electrodes is that they make terrible neighbors. In addition to being enormous compared to the neurons, they are stiff and tend to rub nearby cells the wrong way. The resident immune cells spot the foreigner and attack, inflaming the brain tissue and blocking communication between the electrode and the cells.
The new electrode developed by the teams of Daryl Kipke, a professor of biomedical engineering, Joerg Lahann, a professor of chemical engineering, and Nicholas Kotov, the Joseph B. and Florence V. Cejka Professor of Engineering, is unobtrusive and even friendly in comparison. It is a thread of highly conductive carbon fiber, coated in plastic to block out signals from other neurons. The conductive gel pad at the end cozies up to soft cell membranes, and that close connection means the signals from brain cells come in much clearer.
“It’s a huge step forward,” Kotov said. “This electrode is about seven microns in diameter, or 0.007 millimeters, and its closest competitor is about 25 to 100 microns.”
The gel even speaks the cell’s language, he said. Electrical impulses travel through the brain by movements of ions, or atoms with electric charges, and the signals move through the gel in the same way. On the other side, the carbon fiber responds to the ions by moving electrons, effectively translating the brain’s signal into the language of electronic devices.
To demonstrate how well the electrode listens in on real neurons, Kipke’s team implanted it into the brains of rats. The electrode’s narrow profile allows it to focus on just one neuron, and the team saw this in the sharp electrical signals coming through the fiber. They weren’t getting a muddle of multiple neurons in conversation. In addition to picking up specific signals to send to prosthetics, listening to single neurons could help tease out many of the brain’s big puzzles.
“How neurons are communicating with each other? What are the pathways for information processing in the brain? These are the questions that can be answered in the future with this kind of technique,” Kotov said.
“Because these devices are so small, we can combine them with emerging optical techniques to visually observe what the cells are doing in the brain while listening to their electrical signals,” said Takashi Kozai, who led the project as a student in Kipke’s lab and has since earned his Ph.D. “This will unlock new understanding of how the brain works on the cellular and network level.”
Kipke stressed that the electrode that the team tested is not a clinical trial-ready device, but it shows that efforts to shrink electrodes toward the size of brain cells are paying off.
“The results strongly suggest that creating feasible electrode arrays at these small dimensions is a viable path forward for making longer-lasting devices,” he said.
In order to listen to a neuron for long, or help people control a prosthetic as they do a natural limb, the electrodes need to be able to survive for years in the brain without doing significant damage. With only six weeks of testing, the team couldn’t say for sure how the electrode would fare in the long term, but the results were promising.
“Typically, we saw a peak in immune response at two weeks, then by three weeks it subsided, and by six weeks it had already stabilized,” Kotov said. “That stabilization is the important observation.”
The rat’s neurons and immune system got used to the electrodes, suggesting that the electronic invaders might be able to stay for the long term.
While we won’t see bionic arms or Iron Man-style suits on the market next year, Kipke is optimistic that prosthetic devices could start linking up with the brain in a decade or so.
“The surrounding work of developing very fine robotic control and clinical training protocols—that work is progressing along its own trajectory,” Kipke said.
Kipke, director of the Center for Neural Communication Technology, is a professor of biomedical engineering. Kotov, the Joseph B. and Florence V. Cejka Professor of Engineering, is a professor of biomedical engineering, chemical engineering, biomaterials science and engineering, and macromolecular science and engineering. Lahann, director of the Biointerfaces Institute, is a professor of chemical engineering, materials science and engineering, biomedical engineering, and macromolecular science and engineering.
A paper on the research, “Ultra-small implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces,” is published in the current edition of Nature Materials. The work is funded by the National Institutes of Health and the Center for Neural Communication Technology, an NIH-funded biotechnology research center.
Contact Kate McAlpine, (734) 763-4386, firstname.lastname@example.org or Nicole Casal Moore, (734) 647-7087, email@example.com
Daryl Kipke: http://sitemaker.umich.edu/daryl.kipke/home
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