An Introduction to Tissue Print Technologies with Dr. Sandra Gaston

Question and Answer with Dr. Sandra Gaston of Tufts Medical Center

As a featured speaker for the Biorepositories and Sample Management Summit on October 12-14th, 2015, in Boston, Massachusetts, Dr. Sandra Gaston has presented on “Tissue Print Technologies: An Innovative and Practice Approach to Obtaining High Quality Research Samples from Biopsies and Other Challenging Biospecimens.”

As an attendee and sponsor of the event, I was deeply honored to have the chance to interview Dr. Gaston about about her research techniques, novel approaches to specimen management, and the use of these techniques in precision medicine. Her answers to our interview questions are below.

Question and Answers about Tissue Print Technology

Question 1: What are you speaking about at the “Biorepositories and Sample Management Summit” in Boston?

Dr. Gaston: I'm focusing my talk on the use of innovative tissue print technologies that my laboratory has developed in order to obtain high quality samples from biospecimens like tissue biopsies that are too small to be sampled by conventional methods.

Question 2: What are tissue prints and how would you define them?

Dr. Gaston: Tissue prints are in some ways similar to touch preps, but we use nitrocellulose instead of glass slides to blot the fresh tissue surface and obtain a thin layer of cells and extracellular matrix for molecular biomarker analysis. The tissue print collection technique results in a nitrocellulose blot that can be immediately snap frozen to preserve RNA and DNA quality, and we have used this approach to study gene expression and mutation patterns in needle biopsies without compromising these critical specimens for diagnosis.

Question 3: What is the value of using tissue print technologies?

Dr. Gaston: Tissue print technologies can be readily adapted for collecting high-value samples from biospecimens that can’t be readily sampled by conventional slice or shave methods. Key advantages of tissue print technologies include:
• The collection technique is easily learned by support staff
• The nitrocellulose is inexpensive and widely available
• Tissue prints can be collected quickly both in outpatient and surgical pathology settings
• Tissue prints take up very little space in the freezer
• The “imprint” can be directly aligned with the tissue histology to facilitate biomarker-pathology correlations.

Question 4: What impact is tissue print technology having on the biobanking community?

Dr. Gaston: The major scientific impact of the tissue print technology approach is that it expands the range and representation of biospecimens that are available for analysis.

Question 5: What is your current role at Tufts Medical Center Biorepository?

Dr. Gaston: The Tufts Medical Center Biorepository is a service of the Department of Pathology and Laboratory Medicine. We are accredited by the College of American Pathology (CAP) and affiliated with the NCI Cooperative Human Tissue Network (CHTN). We are a core research resource for Tufts affiliated investigators and for investigators from the larger research community, including scientists from pharma and biotech companies.

Author: This post was written by Cade Hildreth, President/CEO of BioInformant Worldwide, LLC, a market research firm specializing in the stem cell industry. For more conference updates, follow Cade on Twitter (@StemCellMarket) or LinkedIn.

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Challenges in Setting Up a Breast Cancer Oriented Biorepository in Latin America Fully Integrated with an US-based Academic Institution

Translational cancer research is largely made possible through access to large patient clinical databases and high-quality biological samples collected, processed and annotated in a systematic fashion according to international standards.

We thus set out to jointly to establish an Argentinean breast cancer oriented biobank between Baylor College of Medicine (BCM) Cancer Center and the Breast Center in Buenos Aires (BCBA) as a fully integrated and shareable data management system with regards to bio-specimen (blood, non-tumoral breast tissue, breast cancer tissue), pathological, epidemiological and clinical data sets. Of particular interest to us was investigating new breast cancer screening biomarkers and the ability to carry out breast cancer population-science epidemiological studies.

Since variability in bio-specimen collection and processing, as well as in the recording of associated data, are known to potentially affect analytical results, particular attention was paid to the standardization of all such processes in accordance with ISBER’s Best Practice Guidelines for Biorepositories.

Consented individuals at the BCBA were allocated by the treating physician to one of four categories: 

1. 1. Breast cancer
2. 2. Benign breast disease by biopsy
3. 3. High breast cancer risk according to the Gail Model 
4. 4. Healthy controls. 

In breast cancer patients, blood was collected at several stages during their clinical course (pre-surgical, pre-systemic treatment, and, if applicable, in the metastatic stage).  Blood and tissue specimens as well as clinical data from patients with benign lesions and healthy controls (mammoplasty) were also collected and incorporated into the system. All subjects were followed-up at yearly intervals.

We also set out to develop a bilingual (English and Spanish) web-based tool for bio-specimen management, inventory and clinical data registries in full compliance with international standards for data security and quality assurance.

We believe this constitutes a unique approach to breast cancer biobanking including the availability of healthy control and non-cancerous breast tissue subject’s bio-specimen and datasets which can be made seamlessly accessible among two or more institutions.

At this year’s Biorepositories and Sample Management conference, I’ll be presenting on the cultural and regulatory aspects on setting up a biobank in Latin America, expanding from USA/Argentina to Mexico and Brazil as a breast center’s biobank networking.

Hear more from Astrid as this year’s Biorepositories and Sample Management conference.  Download the agenda to see what’s on tap. Save $100 when you register here and use code XP1998BLOG.

About The Author: Astrid Margossian, MD, PhD, is a breast cancer surgeon focused on biobanking. She is the Scientific and Executive Director of the Argentinean Breast Center Buenos Aires Biobank, a branch of the Baylor College of Medicine (BCM) Cancer Center Biorepository, where she holds a position since 2008 engaged in tumor banking and tumor bank management efforts at the Lester and Sue Smith Breast Center, Houston Texas. She also has contributed to the establishment of the Population Sciences Biorepository at BCM’s Dan Duncan Cancer Center.

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1: Biopreserv Biobank. 2014 Apr;12(2):148-50. doi: 10.1089/bio.2013.0091.National Cancer Institute Biospecimen Evidence-Based Practices: a novel approach to pre-analytical standardization.Engel KB1, Vaught J, Moore HM. 

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Top Three Biobanking Challenges Today

The Memorial Sloan Kettering Center is known as the premier cancer research institute in the world.  Needless to say, their research team is well acquainted with some of the challenges the biobanking industry currently faces today.  Who better to provide the latest on the challenges in the field than Vinagolu Rajasekhar, a Senior Research Scientist working on live tissue banking with the Memorial Sloan Kettering Cancer Center and a speaker at this year’s Biorepositories and Sample Management Conference.  He filled us in on what he sees as the three biggest hurdles in the industry today as well as a couple of other minor obstacles. 

What are some of the challenges that you’re experiencing in your industry today?

Raj: I am glad that you brought up this very important point of the present context regarding functional biospecimens and biorepositories. In fact, this is not only the challenge that we face but it is also a challenge for all those striving to succeed in clinical translation studies all over the world.  Particularly as a team member of the Memorial Sloan-Kettering Cancer Center, which you all know as the world premier cancer research institute and also the cancer clinic, my perspective to this query is different from what one may normally expect from industries.

Developing durable and functional therapies against human cancers is the prime challenge for all of us. This is very difficult task to accomplish unless we have set up faithful pre-clinical experimental models that closely mimic that of real time patients’ situations.

Human tumors are generally composed of heterogeneous tissues, I mean multiple cell types within a single tumor mass.  So, it becomes important to comprehend well with the science behind the biospecimens we obtain. Present cancer cell line models and also genetically engineered mouse tumor models would never recapitulate the original patient tumor heterogeneity that we all have to deal with during the real time treatment situations. Particularly, as a Working Group Member of Biospecimen Science in the International Society for Biological and Environmental Repositories (ISBER), and also collaborating with Dr. Fay Betsou at the Integrated Biobank of Luxembourg (IBBL), I must also bring to the light that the most cancer therapeutics developed to date all over the world have also relied on the data obtained from conventional bio-repositories of flash frozen bulk tumor specimens, which might not represent the real time clinical situations.

First, human tumors are also dynamic organs.  Thus, they manifest variability in their tissue heterogeneity during cancer development within an organ. These also add up to inter- and intra- tumor heterogeneities among different foci of the same cancer within the same organ and within the same tumor lesion across the radius or from the center to the margins of the tumor. Therefore, flash frozen tissues are not harmonized specimens.  Studies based on these biospecimens would not reflect the real time patient situation. We are increasingly convinced of the significance of patient specific treatments for cancers from our personal experience with the laboratory bench and at the patient bedside.

Second, the conventional biorepositories are exhaustible and cannot be replenished. So now the prime challenge is to aim at developing live tumor banks that are continuously available, which is a sort of renewable or replenishable as harmonized biospecimens.

Towards this goal, I and Dr. John Healey, the Chief of Orthopedic Surgical Oncology are together developing various live banks of human tumors as viable biorepositories. These live bio-repositories are nothing but patient derived xenograft (PDX) models of human cancers. Here upon our internal review board approved consenting of the cancer patients, we utilize their surgically resected tumor specimens. We transplant the fresh tumor specimens into immunocompromised rodents (mice for example) and follow the development of tumor growth.

Essentially, here patient tumor tissues are transplanted into the mice whose immune system is genetically shut down to facilitate the tumor take-in, and the growth of PDX as clinically relevant experimental models. This approach will facilitate us conveniently harvest sufficient tumor volumes and functionally characterize these tumors at different developmental stages in vivo and in the laboratories. These PDX models would, on the other hand, generate the original patient tumor-specific heterogeneity in real time comparable to that of patient situation. Thus, these models form clinically relevant experimental models for carrying out functional pre-clinical studies. For example, any drugs we identify by screening for the sensitive compounds that affect the growth of the at least early PDX models are expected to be functional in the real patient tumor microenvironment.

Finally, this live biobanking approach can be also utilized in co-clinical trials in terminally ill patients as well as for sharing among different clinical research groups worldwide for facilitating simultaneous global collaborations with relevant tumor types.

In this process, we also encounter some minor technical challenges as well.

For example:  

1. Isolating cells from human tumors present more complex hurdles than that of from the so far relied mouse tumors.  

2. Each organ human tumor type is different from the other organ tumors within the same patient. For instance, the tissue of human brain tumor cannot be the same as another human breast tumor or a liver tumor. So, even to disassociate and extract these cells in functional from, we need to have sound experimental skills and intellectual expertise and a few others of minor importance that we can deal another time.

You can download the full interview with Vinagolu here.

You can hear more from Vinagolu as well as other leaders in the biobanking at the Biorepositories and Sample Management Conference.  Download the agenda here to see what’s on tap.

SAVE $100. Register here and use code XP1998BLOG.

SEE ALSO: FREE WEBINAR- Optimizing Samples for Future Use: Innovative technology to improve the functional quality control of DNA samples

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Show me the (“Fit-for-purpose”) Biospecimen Evidence Based Practices (BEBP’s) Data

By Lisa B Miranda

The term Biospecimen Evidence Based Practices or BEBP’s appears to have been recently coined by colleagues from the United States National Institutes of Health National Cancer Institute Biorepositories and Biospecimen Research Branch.  Last month, Engel et al published an article in Biopreservation and Biobanking titled “National Cancer Institute Evidence Based Practices: A Novel Approach to Pre-Analytical Variability Standardization”. As many in the biobanking field are aware variance in sample management practices can affect biospecimen integrity and often alters quality.   Biobanks typically aim to address this issue via adherence to standard operating procedures and protocols, documentation of any inter-specimen variability for reference during analysis downstream, as well as implementation of automated sample processing technologies, which some believe may reduce technical inconsistencies often found in manual practice.  In Kelly et al’s article the cogent point is made that while internal standardization of biobanking sample management practices aides in optimizing pre-analytical variability of specimens at one’s own site, this does not address the equally important issue of managing variability across biobank sites.   Optimizing and understanding pre-analytical variability across sites is a common issue for an abounding number of biospecimen research collaborations (i.e. multi-center clinical trials) and network based biobanking activities (i.e. aggregation of and analysis samples across sites), etc.  

Looking back in retrospect from last year’s conference while looking prospectively to the 2014 conference, it is clear that quality-driven-collaboration is an ongoing theme echoed again this year by the theme of optimizing quality control and sample integrity.  In my opinion the one thing that ties these two themes together and addresses the issue of cross-site inter-variability is “fit for purpose” evidence based biobanking.   This approach advocates prospective development of BEBP’s, which regardless of site of origin should provide reproducible validated results.  Navigating “fit for purpose” evidence based protocol requirements requires a certain level of precision. Planning of which should be driven by the specimen, molecule and analyte of interest otherwise referred to as an SMA-approach. To increase the likelihood that a biospecimen collection is managed in a fit-for-purpose fashion, it is essential that biobanks and biospecimen resources prospectively define their procedures using an evidence based focus.  What isn’t so apparent is how to get there so that this idea can become a common reality. 

In 2012 I developed a fit-for-purpose evidence based protocol framework which was distributed in its early stages at when IIR’s conference was its 5^th year.  In September I’ll be giving a talk with a colleague at IIR’s 7^th Biorepositories and Sample Management Conference.  The talk will offer insight from a recent collaboration amongst pharmaceutical, academic and biotech colleagues with whom the fit- for- purpose evidence based protocol development framework has been vetted.  In this talk we plan to present a brief overview along with relevant lessons learned, feedback and take homes from presentation and peer based discussion amongst the broader biobanking community.  The technical and scientific framework is meant to function as a quality control instrument, consists of nine sections and is designed to offer utility in a two ways.  Firstly, it can be used as a guidance document (checklist and worksheet) and fit-for-purpose (FFP) planning exercise (to assist biobanks in understanding evidence based biobanking requirements) so that BEBP’s can be established in real time. Secondly, it can be utilized retrospectively as an internal audit tool (to ensure your biobank protocols, operations and equipment can support FFP sample management.)  The comprehensive document factors in best practices as well as relevant reporting guidelines (e.g. BRISQ).  With the advent of biospecimen science leading the way for evidence based biobanking practices, Biobankers have an amazing opportunity to impact both the biomedical research and clinical realms in a significant capacity.  This instrument if implemented across biobank sites could accelerate real time practice of evidence based biobanking and remedy the issue Engel et al raise regarding variability between multiple sites.  If all sites in an organization or collaboration incorporate this framework, they’d be more apt to increase proficiency of biospecimen collection quality and be more adept at ruling out variability between collections across sites.  If this topic and information interests you, we hope to see you at the conference September 8-10, 2014 in Boston.  Check out what we’ve got lined up.

Save your seat now and you could SAVE 15%. Use discount code XP1998BLOG. Register here.

About the Author:  Lisa Miranda is President and Chief Executive Officer of Biobusiness Consulting Incorporated, a biobanking and biotechnology commercialization advisory based in the Greater Boston Area.  She is known worldwide as a biobanking and clinical research subject matter expert.  Much of her work focuses on biobank strategic planning and/or development of biospecimen research applications and biotechnology commercialization.  She may be reached at: lisabmiranda@biobusinessconsulting.com

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Four Reasons "Smart Outsourcing" Biorepositories Can Work for You

This post was authored by Mike Madarasz of the Institute for International Research.  You can follow him on Twitter at @MikeMadarasz

We are at point where researchers from nearly every medical discipline have come to appreciate the importance of having a centralized biorepository and the technological framework to house the data associated with these samples.  Transitioning from a decentralized model of storing these samples to a more centralized method has proved to be difficult and has led many institutions to begin outsourcing this task.  Kristina Robson of BioStorage Technologies says outsourcing is a smart option for companies that don’t have the internal bandwidth or expertise to manage these assets.   “Outsourcing sample management with an experienced service-provider has both financial and operational benefits” explains Robson.    

The operational benefits of some of the sophisticated sample management systems are fairly obvious as these providers offer a high quality, consistent solution for handling samples.  On the financial side, Robson cited a number of drivers that make “smart outsourcing” approaches an attractive option:

Speed — It could take as long as a year to establish a biorepository that can adequately store physical specimens needed to maximize today’s clinical endeavors. Insourcing alleviates this difficulty, as appropriate infrastructure for data management and storage can be developed in a matter of months. 

Decreased Cost — Sample management “smart outsourcing” models reduce infrastructure cost, thereby decreasing the need for large operations teams to manage/map data, provide governance and build custom query application.

Scalability — Because large quantities of biological materials are generated during drug R&D, thousands of samples need to be properly stored and tracked throughout clinical trials and beyond. Through innovative outsourcing partnership models, companies gain the ability to move samples offsite seamlessly to add capacity.

Quality Assurance — By leveraging SOPs already developed and validated by an outsourced partner, risk of specimen degradation through handling and storage techniques can be mitigated. 

You can check out Kristina Robson’s article in its entirety here.

What can these data-rich biorepositories do for your research?  We have the answer.  Join our free webinar- 4/30, 2:00-3:00PM EST.

Register here. DISCOUNT CODE: XP1998BLOG

Need the latest biorepository research? Check out Biorepositories and Sample Management Conference.

September 8-10 | Boston, MA

Why wait? Register now.  DISCOUNT CODE: XP1998BLOG

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Biorepositories: An Interview with Tracie DeHart, Dow Agrosciences

Tracie DeHart, Dow Agrosciences, a speaker at this year's 2010 Biorepositories Conference, recently sat down with Courtney Leonard, the Biorepositories Conference Director to discuss some of the current trends in the biosciences industry..

They discussed:
-Tracie’s background in sample management
-Operating a biorepository in the biopharma industry versus the agrobio industry
-Setting up an in house biorepository
-And more!

Click here to download the transcript, and visit the Biorepositories 2010 webpage to download the podcast.

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New biorepository for Laboratory Corp of America

The Charlotte Business Journal is reporting that the Laboratory Corp of America is moving to a new biorepository in Kannapolis, North Carolina. This new biorepository will be one of the largest in the world with over 40,000 square feet. Read more here.

If you're interested in networking with other professinals in the biorepository field, join us here at the Biorepositories LinkedIn Group!

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