Are cellular technologies scalable?

Are cellular technologies scalable? According to Phillip Vanek, Head of Innovation at Lonza Bioscience, the answer to this question is “yes”, but only if scaling is considered very early in the technology’s development. Vanek addressed the topic of scalability at his talk at the INBT symposium.

scalabilityScaling-up of bench-top science into industrial processes is difficult for a number of reasons. Commercial-scale production of cell-based products introduces regulatory challenges and production volumes never encountered on the bench scale. Even the basic laboratory chore of cell passage can become a large hurdle when attempting to grow large number of cells in the multi-layered cell factory system.

With such challenges in mind, Vanek lays out a number of ways to improve the success rate of scaling up processes. He stressed that a process should ideally be closed for maximum success. A closed process prevents product contamination and minimizes user error. Also, maximizing automation helps minimize operator error in processing.

Most importantly, the treatable patient pool sizes and dosage requirements need to be well-known for a process to be commercially successful. Vanek concluded that cellular technologies are scalable, but only if researchers start with end goals in mind early and are well-aware of potential pitfalls.

Lonza 

Editor’s Note: This 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 Christian Pick, a doctoral candidate in the chemical and biomolecular engineering laboratory of Joelle Frechette. Look for other symposium summaries on the INBT blog.

 

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. 

Overcoming drug delivery barriers

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.

Nanotechnology bears a multitude of possibilities to systematically and specifically treat many well-characterized and currently untreatable diseases.  Despite this, there exist multiple barriers to its development including challenges related to delivery in the human body.

justin_hanes

Justin Hanes, a professor of Chemical and Biomolecular Engineering at Johns Hopkins University, highlighted some of the exciting advances that his laboratory has developed to overcoming these challenges.  According to Hanes, one of the primary functions of nanobiotechnology is to enable a therapy to be delivered to a specific location and only remain there for as long as it is needed.  He likened this idea to applying weed poison to a rose garden.  You only want to apply a little bit of poison to a targeted area, not flood the whole garden.  Unfortunately conventional cancer chemotherapy is like flooding the garden, but only 1 percent of the drug reaches the tumor.  Hanes stated the goal of his work is to flip that so that all but 1 percent of the drug makes it to the site of delivery.

With that in mind, Hanes summarized two stories from his lab of ideas that are successfully being translated from bench to bedside.  One therapy involves the use of custom designed nanoparticles that are capable of penetrating the mucus layers of various human tissues to enable a controlled release of drug into the body.  The second therapy involves the use of injectable particles to the eye that inhibit blood vessel formation,  which is related to diseases such as macular degeneration.

These therapies are being developed by biotech companies launched by Hanes, GrayBug and Kala Pharmaceuticals.

Tumor cells change when put into a ‘tight spot’

Konstantinos Konstantopoulos addresses audience at 2012 NanoBio Symposium. Photo by Mary Spiro/JHU

“Cell migration represents a key aspect of cancer metastasis,” said Konstantinos Konstantopoulos, professor and chair of the Department of Chemical and Biomolecular Engineering at Johns Hopkins University. Konstantopoulos was among the invited faculty speakers for the 2012 NanoBio Symposium.

Cancer metastasis, the migration of cancer cells from a primary tumor to other parts of the body, represents an important topic among professors affiliated with Johns Hopkins Institute for NanoBioTechnology. Surprisingly, 90 percent of cancer deaths are caused from this spread, not from the primary tumor alone. Konstantopoulos and his lab group are working to understand the metastatic process better so that effective preventions and treatments can be established. His students have studied metastatic breast cancer cells in the lab by tracking their migration patterns. The group has fabricated a microfluidic-based cell migration chamber that contains channels of varying widths. Cells are seeded at one opening of the channels, and fetal bovine serum is used as a chemoattractant at the other opening of the channels to induce the cells to move across. These channels can be as big as 50 µm wide, where cells can spread out to the fullest extent, or as small as 3 µm wide, where cells have to narrowly squeeze themselves to fit through.

A current dogma in the field of cell migration is that actin polymerization and actomyosin contractility give cells the flexibility they need to protrude and contract across a matrix in order to migrate. When Konstantopoulos’s students observed cells in the wide, 50 µm-wide channels, they saw actin distributed over the entirety of the cells, as expected. They also observed that when the cells were treated with drugs that inhibited actin polymerization and actomyosin contractility, they did not migrate across the channels, also as expected.

However, when the students observed cells in the narrow, 3 µm-wide channels, they were surprised to see actin only at the leading and trailing edges of the cells. Additionally, the inhibition of actin polymerization and actomyosin contractility did not affect the cells’ ability to migrate.

“Actin polymerization and actomyosin contractility are critical for 2D cell migration but dispensable for migration through narrow channels,” concluded Konstantopoulos. The data challenged what many had previously believed about cell migration by showing that cells in confined spaces did not need these actin components to migrate.

These findings are indeed important in the context of cancer metastasis, where cells must migrate through a heterogeneous environment of both wide and narrow areas. Konstantopoulos’s data gives a better mechanistic understanding of the different methods cancer cells use to migrate in diverse surroundings.

Future studies in the Konstantopoulos lab will focus on how tumor cells decide which migratory paths to take. INBT-sponsored graduate student Colin Paul has developed an additional microfluidic device that contains channels with bifurcations. He hopes to determine what factors guide a cell in one direction versus another. The Konstantopoulos lab hopes to continue to understand exactly how tumor cells migrate so that new therapies can eventually be developed to stop metastasis.

Story by Allison Chambliss, a Ph.D. student in the Department of Chemical and Biomolecular Engineering with interests in cellular biophysics and epigenetics.

Watch a video related to this research here.

Konstantopoulos reported these findings in October 2012 The Journal of the Federation of American Societies for Experimental Biology.  Read the article online here.

 

Four students honored at INBT research symposium

Spyros Stamatelos with INBT director Peter Searson. Photo by Mary Spiro

Four students were honored for their research efforts at Johns Hopkins Institute for NanoBioTechnology’s sixth annual symposium. A poster session with more than 75 research posters from every division of the university was held in the afternoon and four posters were selected for top honors.

A poster by Yu-Ja Huang, Justin Samorajski, Rachel Kreimer, Denis Wirtz and Peter Searson won first prize, and first author Huang was awarded the $200 gift card from Best Buy. Their poster was entitleThe Influence of Electric Field and Confinement on U-87 Glioblastoma Cells.

Jack Andraka describing his research at the INBT poster session. Photo by Mary Spiro

Taking second place was Anirudha Sing, Jianan Zhan and Jennifer Elisseeff with the poster Directed Stem Cell Differentiation Using PEG-alpha CD-derived biomaterials. First author Singh claimed the $100 Best Buy card.

A $50 Best Buy card was presented to Spyros Stamatelos who was first author with Eugene Kim, Arvind Pathak and Aleksander Popel on the poster Characterization of the Heterogeneity of Tumor Vasculature using Hemodynamic Modeling and High Resolution Imaging Implications for Drug Delivery.

Honorable mention was given to Jack Andraka, a high school research intern in the lab of Anirban Maitra who worked with Venugopal Chenna. Andraka’s poster, A Novel Paper Sensor for the Detection of Pancreatic Cancer, helped him win a free book from Springer.

The event was held  at the Johns Hopkins medical campus in the Owens Auditorium on May 4 with six faculty expert speakers and approximately 400 people in attendance.

Students talk cancer nanotech at Homewood March 21

Students affiliated with the Center of Cancer Nanotechnology Excellence (CCNE) and the Physical Sciences-Oncology Center (PS-OC) at Johns Hopkins University have organized a spring mini-symposium for March 21, 10 a.m. in the Hackerman Hall Auditorium at the Johns Hopkins University Homewood campus.

The student-run mini-symposiums aim to bring together researchers from across the campus affiliated with the PS-OC and CCNE. Graduate students training in these centers, both administered by Johns Hopkins Institute for NanoBioTechnology, work in various disciplines from physics to engineering to the basic biological sciences but with an emphasis on understanding cancer metastasis and developing methods for cancer diagnosis or therapy.

The invited speaker for the symposium is postdoctoral researcher Megan Ho of Duke University. Ho earned her PhD in mechanical engineering in the Wang lab in 2008. She is currently focused on developing microfluidic devices to investigate and control the fundamental reactions that form nanocomplexes for gene delivery. (10 a.m.)

Student apeakers, who will talk for 15 minutes, include:

  • Jane Chisholm (Justin Hanes lab/Ophthalmology): Cisplatin nanocomplexes for the local treatment of small cell lung cancer (10:20 a.m.)
  • Yunke Song (Jeff Wang Lab/Mechanical Engineering): Single Quantum Dot-Based Multiplexed Point Mutation Detection by Gap Ligase Chain Reaction (10:35 a.m.)
  • Andrew Wong (Peter Searson Lab/Materials Science and Engineering): Intravisation into an artificial blood vessel (10:50 a.m.)
  • Brian Keeley: (Jeff Wang Lab/Mechanical Engineering): Overcoming detection limitations of DNA methylation in plasma and serum of cancer patients through utilization of nanotechnology. (11:05 a.m.)
  • Sebastian Barretto (Sharon Gerecht Lab/Chemical and Biomolecular Engineering): Development of Hydrogel Microfibers to Study Angiogenesis (11:20 a.m.)

View the symposium flyer here. The mini-symposium is free and open to the entire Johns Hopkins University community. No RSVP is required, although seating is limited.

Johns Hopkins Physical Sciences-Oncology Center

Center of Cancer Nanotechnology Excellence

Hopkins to host colloid, surface science symposium

The Johns Hopkins University is hosting the 86th American Chemical Society’s Colloid and Surface Science Symposium in Baltimore, MD on June 10-13, 2012. The meeting includes 13 parallel sessions, a poster session, 28 invited speakers, and 28 session organizers. A new addition to this meeting is the Langmuir Student Awards presentation session with application details given on the conference website.

Abstract submission is now open and the deadline is February 7, 2012. Up-to-date information on the meeting can be found at the website: www.colloids2012.org.

For further details about this meeting please contact the symposium co-organizers Mike Bevan (mabevan@jhu.edu) and Joelle Frechette (jfrechette@jhu.edu). Bevan and Frechette are affiliated faculty members of Johns Hopkins Institute for NanoBioTechnology and members of the Department of Chemical and Biomolecular Engineering.

Download the symposium flyer here.

 

Agenda set for Oct. 10 mini-symposium on cancer, nanotech

From the spring mini-symposium.

Johns Hopkins Physical Sciences-Oncology Center and Center of Cancer Nanotechnology Excellence will host a mini-symposium on Monday Oct., 10 in the Hackerman Hall Auditorium. Talks on topics related to cancer and nanotechnology begin at 9 a.m.

Speakers include:

  • 9:15 a.m.: The pulsating motion of breast cancer cell is regulated by surrounding epithelial cells. Speaker: Meng Horng Lee
  • 9:40 a.m.: Breast tumor extracellular matrix promotes vasculogenesis. Speaker: Abigail Hielscher
  • 10:00 a.m.: Attachment to growth substrate regulates expression of GDF15, an important molecule in metastatic cancer. Speaker: Koh Meng Aw Yong
  • 10:20 a.m.: Mucin 16 is a functional selectin ligand on pancreatic cancer cells. Speaker: Jack Chen
  • 10:40 a.m.: Particle tracking in vivo. Speaker: Pei-Hsun Wu

These talks are open to the entire Hopkins community. No RSVP is required. Refreshments will be served.

 

 

Breast cancer highlighted at Homewood mini-symposium

A tumor cell breaking free and entering the blood stream. (From animation by Ella McCrea, Nathan Weiss and Martin Rietveld)

Breast cancer will be topic of at least two of the talks planned for a mini-symposium October 10 on the Homewood campus.

UPDATED: Click here for updated list of talk titles.

Students from Johns Hopkins Physical Sciences-Oncology Center (PSOC) and Center of Cancer Nanotechnology Excellence (CCNE) will hold their second mini-symposium of the year on October 10 at 9 a.m. in Hackerman Hall Auditorium. The symposia, scheduled each spring and fall on the Homewood campus, encourage an exchange of ideas between PhD students and postdoctoral fellows associated with these centers. The entire Hopkins community is invited to attend, and no RSVP is required.

Some of the talk titles include, from the department of Chemical and Biomolecular Engineering, “The Pulsing Motion of Breast Cancer Cell is Regulated by Surrounding Epithelial Cells” presented by Meng Horng Lee, a PSOC postdoctoral fellow in the Denis Wirtz lab; “Breast Tumor Extracellular Matrix Promotes Vasculogenesis” presented by Abigail Hielscher, a postdoctoral fellow in the Sharon Gerecht lab; and “Mucin 16 is a Functional Selectin Ligand on Pancreatic Cancer Cells” given by Jack Chen, a pre-doctoral fellow in the lab of Konstantinos Konstantopoulos. Additional speakers include postdoctoral fellow Pei-Hsun Wu, PhD, a from the Wirtz Lab and Koh Meng Aw Yong, a pre-doctoral student affiliated with Princeton University’s Physical Sciences-Oncology Center.

The purpose of these twice a year, student run mini-symposia is to facilitate communication among researchers working in laboratories studying the mechanistic aspects of cancer spread (i.e., those affiliated with the PSOC) and those working on novel means of using nanotechnology for cancer diagnosis or treatment (i.e., those associated with the CCNE). Anjil Giri coordinated the fall mini-symposium, a PSOC pre-doctoral fellow in the Wirtz lab , with Erbil Abaci, a PSOC pre-doctoral fellow with in the Gerecht lab. Visit the INBT website (inbt.jhu.edu) for further details, as additional speakers and talk titles will be announced.

Hopkins Imaging Initiative to host first annual conference

The Johns Hopkins University Imaging Initiative will host the first annual Imaging Conference, October 6, 2011 at the Turner Auditorium on the medical campus. The conference features afternoon lectures from various Hopkins faculty followed by a research poster session and happy hour. Anyone interested in imaging is welcome to attend.

Speakers include Elliot McVeigh, director of the Department of Biomedical Engineering; Elliot Fishman, MD, director of diagnostic imaging at body CT at Johns Hopkins Hospital; Jerry Prince, the William B. Kouwenhoven Professor of Electrical and Computer Engineering at the Whiting School of Engineering; Xingde Li, associate professor of biomedical engineering and head of the Laboratory of Biophotonics Imaging and Therapy at the Whiting School; Peter van Zijl, professor of radiology at the school of medicine and director of the F.M. Kirby Research Center for Functional Brain Imaging; and several others to be announced.

Abstracts will be accepted until Sept 6 and conference registration will be accepted until October 1. For complete information about this event and to register, go to http://imaging.jhu.edu/conferences/imaging-conference-2011