Stem Cell Science, Engineering theme of May 2 symposium

Johns Hopkins Institute for Nanobiotechnology is now accepting posters for its annual symposium to be held May 2 at Owens Auditorium (located between CRB I and CRB II) at the School of Medicine. Deadline for poster registration is April 30. Top presenters are eligible to win one of three NIKON cameras.

All disciplines and topics are encouraged to register, even if not related to theme.

Go to this link for full agenda and to register.

nano-bio-symposium-14-flyer (2)The theme this year is Stem Cell Science and Engineering: State-of-the-Art. Speakers start at 9 a.m. through noon. Then at 1:30 there will be a poster session where students across Johns Hopkins will present some of their current research findings. Judges have been selected from industry and the university. Don’t miss this exciting exploration of how scientists, engineers and clinicians can work together with stem cells to solve some of humanities pressing problems in health and medicine.

This year’s speakers and talk titles include:

• 8:30-9 am Registration Lobby of Owens Auditorium

• 9:00-9:05 Welcome and Introduction of speakers Peter Searson

• 9:05-9:35 Human cell engineering: recent progress in reprogramming cell fates and editing the nuclear genome, Linzhao Cheng

• 9:35-10:05 Regenerating Musculoskeletal Tissues from Fat, Warren Grayson

• 10:05-10:35 Hitting the Bull’s Eye: Targeting HMGA1 in Cancer Stem Cells using Nanotechnology, Linda M. S. Resar

• 10:35-10:45 Coffee Break

• 10:45-11:15 Engineering biomaterials to enhance stem cell potential, Hai-Quan Mao

• 11:15 -11:45 Engineered Human Pluripotent Stem Cells for Disease Modeling Applications, Mark Powers

• 11:45-12:15 Understanding the function of risk genes for mental disorders using iPSC models, Guo-li Ming

Lunch break

• 1:30-3:30 pm Poster Sessions Owens Corridor

• 3:30 Announcement of Poster Session Winners/Adjourn

 

 

 

“Cells Performing Secret Handshake” wins grand prize

Sebastian F. Barreto, a doctoral student of chemical and biomolecular engineering in the laboratory of Sharon Gerecht, won the grand prize for his image “Cells Performing Secret Handshake” from the Regenerative Medicine Foundation. Another image that Barreto submitted received 3rd place (shown below), and a third image received honorable mention.

Late last year, RMF issued an international call for macro-photography of regenerative medicine images taken through a microscope. This inaugural contest resulted in nearly 100 images representing scientists from the United States, Australia, Canada, Germany, the Netherlands and the United Kingdom.

Cells-Performing-Secret-Handshakes

This image by Sebastian Barreto of Human Umbilical Vein Endothelial Cells “performing a secret handshake” won the grand prize in the first photo contest of the Regenerative Medicine Foundation.

Barreto’s image was included in the “Art of Science: Under the Surface” exhibition that featured an opening lecture and public reception with global expert in regenerative medicine Anthony Atala, M.D. and award winning photographer, painter and sculpture, Kelly Milukas, whose talk focused on the impact of art on healing. The winning images will also be featured in a special public patron gallery exhibition component during the Regenerative Medicine Foundation annual meeting held in San Francisco, May 5-7, 2014.

In a congratulatory letter, Joan F. Schanck, the Academic Research Program Officer, Wake Forest Institute for Regenerative Medicine and Director of Education for the Regenerative Medicine Foundation, said, “This competition will assist in developing a digital library that can be used to excite, inform and educate a broad audience.”

Barreto is affiliated with both the Johns Hopkins Institute for NanoBioTechnology and with the Physical Sciences-Oncology Center.

Captions for both photos can be found below:

Technical description for the grand prize photo: Epifluorescence image was taken at 1280 x 1024 using an Olympus BX60 microscope. Human Umbilical Vein Endothelial Cells (HUVECs) were cultured for five days and stained for F-actin (green), Vascular Endothelial cadherin (VEcad; red), and nuclei was counter-stained with DAPI (blue).

 

Endothelial-Cells-Resisting-Smooth-Muscle-Cell-Pull

Barreto’s image of endothelial cells won 3rd place in the RMF photo contest.

 

Technical description for 3rd place photo: Epifluorescence image was taken at 1280 x 1024 using an Olympus BX60 microscope. Human Endothelial Colony Forming Cells (ECFCs) were cultured for eight days before being co-cultured with human Smooth Muscle Cells (SMCs) for four more days. ECFCs were stained with CD31 (red), SMCs with SM22 (green), and nuclei was counterstained with DAPI (blue).

 

 

 

What Does This Do? Reprogramming Adult Cells to an Embryonic State

The myriad array of cell types that comprise the complex human anatomy is captivating in itself, but in my opinion, the realization that they find their roots in a single population of specialized cells is astounding. Stem cells, with the unique capacity to differentiate into mature cells and divide into identical copies without differentiating, undergo a tightly regulated developmental scheme during embryogenesis to eventually form a fully functional adult.

Although all of our fully matured cells are genetically the same, the differences in cellular functionality can be attributed to variations in gene expression. But what is a gene and what does it do?

A colony of induced pluripotent stem cells.  The colonies are grown on a feed layer which consists of mouse embryonic fibroblasts that help to maintain the stem cells in an undifferentiated state.

A colony of induced pluripotent stem cells. The colonies are grown on a feed layer which consists of mouse embryonic fibroblasts that help to maintain the stem cells in an undifferentiated state.

A molecular instruction manual or gene is a region of DNA; this gene encodes for the synthesis of proteins, which in turn become our functional molecular building blocks. There are many steps that regulate the degree of how our genetic code is transcribed and translated into protein, which are essential components in stem cell behavior.

Researchers are looking to harness the properties of stem cells for regenerative medicine applications. In addition to a steady decrease in donor organ supply as the population continues to age, complications commonly arise due to immune rejection post-surgical treatment. Through cellular therapy, stem cells can be used to replace diseased or damage tissues and organs, circumventing the current issues in surgically implanting donor organs.

Although the utilization of stem cells in a clinical setting sounds promising, both ethical and research concerns must be carefully considered. Looking through a research lens, stem cells can either be harvested from embryos or from adult sources with differing capacities to transform, namely embryonic sources can differentiate to any cell type known as pluripotency, while adult sources have limited potency.

In addition, ethical concerns arise in extracting stem cells from embryonic sources because the embryo is destroyed in the process. These challenges have led researchers to evaluate which key components directs a stem cells ability to differentiate, and if these factors can be used to coax mature cells to revert back to a stem like state with the ability to transform.

In 2012 Drs. Yamanaka and Gurdon were awarded the noble prize in Physiology and Medicine for their discoveries leading to the successful reprogramming of mature cells to stem cells by re-expressing key genes in their DNA. New techniques for controlling gene expression for inducing adult cell pluripotency are emerging with greater efficiencies, providing new strides in the success of regenerative medicine. In fact, I don’t think it’s too far fetched to imagine a day where we use our own cells for personalized disease treatment, thanks to the amazing abilities of genes, and the power to control their expression.

Quinton Smith is a second year graduate student conducting research under the advisement of Sharon Gerecht in the Department of Chemical and Biomolecular Engineering.

Mesenchymal stem cell-based therapies offer hope

Editor’s Note: The following is a summary of one of the talks from the 2013 Nano-bio Symposium hosted by Johns Hopkins Institute for NanoBioTechnology held May 17. This summary was written by Randall Meyer, a doctoral candidate in the biomedical engineering and a member of the Cancer Nanotechnology Training Center. Look for other symposium summaries on the INBT blog.

Among many of the therapies developed over the past several years, stem cells remain one of the most promising for purposes of regeneration, autoimmune disease, and cancer treatment.

Gabriele Todd of Osiris Therapeutics.

Gabriele Todd of Osiris Therapeutics.

Gabrielle Todd, a senior scientist at Osiris Therapeutics, explained some the new mesenchymal stem cell (MSC) based therapies that the company has been developing over the past several years during her talk at the annual Nano-Bio Symposium, hosted by Johns Hopkins Institute for NanoBioTechnology.

The key features that make MSCs such an attractive option is their ability to be isolated from a patient, expanded ex vivo, and re-infused into the same or possibly a different patient. Once inside the body they will home to the site of trouble and release anti-inflammatory and regenerative signals to the damaged tissue. In addition, these cells are what is known as “immune privileged,” in that they lack the necessary signals to trigger an immune response, customary in other transfusions.

Todd summarized some applications on which the company is currently working. One is an MSC-based therapy that utilizes the unique properties of these cells to treat a wide variety of immune related diseases such as graft vs. host disease, Crohn’s disease, and tissue damage from cardiac arrest to juvenile diabetes.

A second application is a product that utilizes MSCs immobilized in a membrane and applied to the site of an external wound. This cells then mediate regeneration of the external tissues, allowing for more efficient healing.

Todd reports that some of these therapies could be available on the market in the coming years.

Osiris Therapeutics, Inc. 

Pluripotent stem cells hold key to blood vessel formation

Pluripotent stem cells, those cells capable of transforming into any type of tissue in the human body, hold the key to one of science’s biggest challenges: the formation of new blood vessels.

Researchers in the laboratory of Sharon Gerecht, associate professor of chemical and biomolecular engineering in the Whiting School of Engineering at Johns Hopkins University, have demonstrated a method that causes these powerful cells to form a fresh network of blood vessels when transplanted in mice. Shawna Williams, writer at the Johns Hopkins School of Medicine, reports here on this new research, which was published online this week in the Proceedings of the National Academy of Sciences. You can find the article here.

Shown are lab-grown human blood vessel networks (red) incorporating into and around mouse networks (green). (Gerecht Lab/PNAS)

Shown are lab-grown human blood vessel networks (red) incorporating into and around mouse networks (green). (Gerecht Lab/PNAS)

Here’s a comment from Gerecht, who is affiliated with both Johns Hopkins Physical Sciences–Oncology Center and Institute for NanoBioTechnology:

“In demonstrating the ability to rebuild a microvascular bed in a clinically relevant manner, we have made an important step toward the construction of blood vessels for therapeutic use … Our findings could yield more effective treatments for patients afflicted with burns, diabetic complications and other conditions in which vasculature function is compromised.”

The Gerecht lab, in collaboration with researchers at the School of Medicine, has been working on this puzzle for some time. One important stride in this current work is that the vessels are forming and persisting in a living animal and not just in a culture in a flask.

Says lead author and doctoral student in biomedical engineering, Sravanti Kusuma:

“That these vessels survive and function inside a living animal is a crucial step in getting them to medical application.”

You can read about some of the Gerecht lab’s previous findings in this particular pursuit in the articles listed below:

Engineers Coax Stem Cells to Diversify 

Research Seeks to Turn Stem Cells into Blood Vessels

 

INBT engineers coax stem cells to diversify

Growing new blood vessels in the lab is a tough challenge, but a Johns Hopkins engineering team has solved a major stumbling block: how to prod stem cells to become two different types of tissue that are needed to build tiny networks of veins and arteries.

The team’s solution is detailed in an article appearing in the January 2013 print edition of the journal Cardiovascular Research. The article also was published recently in the journal’s online edition. The work is important because networks of new blood vessels, assembled in the lab for transplanting into patients, could be a boon to people whose circulatory systems have been damaged by heart disease, diabetes and other illnesses.

blood-vessel-3-72

Illustration by Maureen Wanjare

“That’s our long-term goal—to give doctors a new tool to treat patients who have problems in the pipelines that carry blood through their bodies,” said Sharon Gerecht, an assistant professor of chemical and biomolecular engineering who led the research team. “Finding out how to steer these stem cells into becoming critical building blocks to make these blood vessel networks is an important step.”

In the new research paper, the Gerecht team focused on vascular smooth muscle cells, which are found within the walls of blood vessels. Two types have been identified: synthetic smooth muscle cells, which migrate through the surrounding tissue, continue to divide and help support the newly formed blood vessels; and contractile smooth muscles cells, which remain in place, stabilize the growth of new blood vessels and help them maintain proper blood pressure.

To produce these smooth muscle cells, Gerecht’s lab has been experimenting with both National Institutes of Health-approved human embryonic stem cells and induced pluripotent stem cells. The induced pluripotent stem cells are adult cells that have been genetically reprogrammed to act like embryonic stem cells. Stem cells are used in this research because they possess the potential to transform into specific types of cells needed by particular organs within the body.

In an earlier study supervised by Gerecht, her team was able to coax stem cells to become a type of tissue that resembled smooth muscle cells but didn’t quite behave properly. In the new experiments, the researchers tried adding various concentrations of growth factor and serum to the previous cells. Growth factor is the “food’ that the cells consume; serum is a liquid component that contains blood cells.

“When we added more of the growth factor and serum, the stem cells turned into synthetic smooth muscle cells,” Gerecht said. “When we provided a much smaller amount of these materials, they became contractile smooth muscles cells.”

This ability to control the type of smooth muscle cells formed in the lab could be critical in developing new blood vessel networks, she said. “When we’re building a pipeline to carry blood, you need the contractile cells to provide structure and stability,” she added. “But in working with very small blood vessels, the migrating synthetic cells can be more useful.”

In cancer, small blood vessels are formed to nourish the growing tumor. The current work could also help researchers understand how blood vessels are stabilized in tumors, which could be useful in the treatment of cancer.

“We still have a lot more research to do before we can build complete new blood vessel networks in the lab,” Gerecht said, “but our progress in controlling the fate of these stem cells appears to be a big step in the right direction.”

In addition to her faculty appointment with Johns Hopkins’ Whiting School of Engineering, Gerecht is affiliated with the university’s Institute for NanoBioTechnology (INBT) and the Johns Hopkins Engineering in Oncology Center.

The lead author of the new Cardiovascular Research paper is Maureen Wanjare, a doctoral student in Gerecht’s lab who is supported both by the INBT, through a National Science Foundation Integrative Graduate Education and Research Traineeship, and by the NIH. Coauthors of the study are Gerecht and Frederick Kuo, who participated in the research as an undergraduate majoring in chemical and biomolecular engineering. The human induced pluripotent stem cells used in the study were provided by Linzhao Cheng, a hematology professor in the Johns Hopkins School of Medicine.

This research was supported by an American Heart Association Scientist Development Grant and NIH grant R01HL107938.

Original press release can be found here.

 

Nanoscale scaffolds spur stem cells to cartilage repair

Scanning electron micrographs showing chondroitin sulfate (CS) and poly(vinyl alcohol)-methacrylate (PVA) nanofibers after electrospinning and processing to render the nanofiber scaffolds water-insoluble. Image by Jeannine Coburn/JHU first appeared in PNAS.

A spun 3-D scaffold of nanofibers did a better job of producing larger quantities of and a more durable type of the cartilage protein than flat, 2-D sheets of fibers did. 

Johns Hopkins tissue engineers have used tiny, artificial fiber scaffolds thousands of times smaller than a human hair to help coax stem cells into developing into cartilage, the shock-absorbing lining of elbows and knees that often wears thin from injury or age.

Reporting online June 4 in the Proceedings of the National Academy of Sciences, investigators say they have produced an important component of cartilage in both laboratory and animal models. While the findings are still years away from use in people, the researchers say the results hold promise for devising new techniques to help the millions who endure joint pain.

“Joint pain affects the quality of life of millions of people. Rather than just patching the problem with short-term fixes, like surgical procedures such as microfracture, we’re building a temporary template that mimics the cartilage cell’s natural environment, and taking advantage of nature’s signals to biologically repair cartilage damage,” says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Translational Tissue Engineering Center at the Johns Hopkins University School of Medicine. Elisseeff is also an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology.

Unlike skin, cartilage can’t repair itself when damaged. For the last decade, Elisseeff’s team has been trying to better understand the development and growth of cartilage cells called chondrocytes, while also trying to build scaffolding that mimics the cartilage cell environment and generates new cartilage tissue. This environment is a three-dimensional mix of protein fibers and gel that provides support to connective tissue throughout the body, as well as physical and biological cues for cells to grow and differentiate.

In the laboratory, the researchers created a nanofiber-based network using a process called electrospinning, which entails shooting a polymer stream onto a charged platform, and added chondroitin sulfate — a compound commonly found in many joint supplements — to serve as a growth trigger. After characterizing the fibers, they made a number of different scaffolds from either spun polymer or spun polymer plus chondroitin. They then used goat bone marrow-derived stem cells (a widely used model) and seeded them in various scaffolds to see how stem cells responded to the material.

Elisseeff and her team watched the cells grow and found that compared to cells growing without scaffold, these cells developed into more voluminous, cartilage-like tissue.

“The nanofibers provided a platform where a larger volume of tissue could be produced,” says Elisseeff, adding that three-dimensional nanofiber scaffolds were more useful than the more common nanofiber sheets for studying cartilage defects in humans.

The investigators then tested their system in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats, and compared the results to damaged cartilage in knees left alone.

They found that the use of the nanofiber scaffolds improved tissue development and repair as measured by the production of collagen, a component of cartilage. The nanofiber scaffolds resulted in greater production of a more durable type of collagen, which is usually lacking in surgically repaired cartilage tissue. In rats, for example, they found that the limbs with damaged cartilage treated with nanofiber scaffolds generated a higher percentage of the more durable collagen (type 2) than those damaged areas that were left untreated.

“Whereas scaffolds are generally pretty good at regenerating cartilage protein components in cartilage repair, there is often a lot of scar tissue-related type 1 collagen produced, which isn’t as strong,” says Elisseeff. “We found that our system generated more type 2 collagen, which ensures that cartilage lasts longer.”

“Creating a nanofiber network that enables us to more equally distribute cells and more closely mirror the actual cartilage extracellular environment are important advances in our work and in the field. These results are very promising,” she says.

Other authors included Jeannine M. Coburn, Matthew Gibson, Sean Monagle and Zachary Patterson, all from The Johns Hopkins University.

From a press release by Audrey Huang.

 

Gerecht wins NSF CAREER Award for work in blood vessel formation

Sharon Gerecht (Photo:Will Kirk/JHU)

Sharon Gerecht, assistant professor in Chemical and Biomolecular Engineering at Johns Hopkins University, has been awarded the Faculty Early Career Development (CAREER) Award from the National Science Foundation. The $450,000 prize over five years will help Gerecht in her investigation into how hypoxia, or decreased oxygen, affects the development of blood vessels.

Gerecht’s interdisciplinary research brings together her expertise in stem cell and vascular biology with her background in engineering.  Gerecht said she hopes to discover the mechanisms and pathways involved in the formation of vascular networks, as they relate to embryonic development and diseases such as cancer.

Many medical conditions, such as cancer and heart disease, create areas of decreased oxygen or hypoxia in the spaces between cells. But oxygen is required to maintain normal tissue function by blood vessel networks, which bring nutrients to cells. Likewise, the differentiation of stem cells into more complex organs and structures needs a plentiful supply of oxygen from the vasculature to function.

Gerecht’s study will examine how low oxygen levels impact the growth factors responsible for promoting vascular networks. She also will study the growth of vascular networks in engineered hydrogels that mimic the physical attributes of the extracellular matrix, which is the framework upon which cells divide and grow. Finally, her laboratory will focus on discovering how stem cells differentiate to blood vessel cells and assemble into networks under hypoxic conditions.

She will conduct her research through her role as a project director at the Johns Hopkins Engineering in Oncology Center (EOC), a Physical Science-Oncology Center of the National Cancer Institute. Gerecht is also an associated faculty member of the Johns Hopkins Institute for NanoBioTechnology, which administers the EOC.

Gerecht earned her doctoral degree from Technion – Israel Institute of Technology followed by postdoctoral training at Massachusetts Institute of Technology. She joined the faculty of the Whiting School of Engineering at Johns Hopkins in 2007.

The prestigious CAREER award, given to faculty members at the beginning of their academic careers, is one of NSF’s most competitive awards and emphasizes high-quality research and novel education initiatives. It provides funding so that young investigators have the opportunity to focus more intently on furthering their research careers.

Story by Mary Spiro