Cancer Center

The Tissue Engineering Core at the Tufts Medical Center Cancer Center provides the medical and academic community with experimental in vitro and in vivo three-dimensional (3D) human tissue models.

These tissue models mimic the tissue architecture and signaling networks in human cancers. Through these 3D human tissue models, the program’s services help to meet the growing needs of Cancer Center members and academic investigators to translate basic science discoveries made in rudimentary 2D cultures to more complex tissue models, giving those discoveries greater clinical relevance.

These tissue models offer a more reliable correlation between in vitro studies and in vivo outcomes, while providing a “pre-clinical” experimental setting to screen agents that can accelerate discovery and development of potential therapeutics for clinical application.

Through the fabrication and analysis of 3D tissues, we create novel experimental paradigms that will:

• Enable investigation into the complex interplay between multiple cell and tissue types in a 3D tissue context that are critical factors in cancer progression.
• Provide a more global picture of human disease-associated pathways and their local microenvironment that can be used for target identification, validation, and interrogation.
• Serve as human, “pre-clinical” or “surrogate” tissues to translate discoveries to the clinic.
• Significantly support programs in experimental therapeutics by enabling drug development and discovery by testing lead compounds in 3D tissues rather than in currently existing cell-based assays, prior to testing these compounds in human tissues in vivo.

We offer the following services to the medical community:

Fabrication of 3D tissues that mimic human cancer

• Construction of in vitro “surrogate” tissues comprised of epithelial and mesenchymal cells from a variety of cancer and normal sources
• Generation of 3D tissues with a broad variety of stromal matrices and scaffolds to mimic microenvironmental conditions that regulate tumorigenesis
• Transplantation of engineered 3D tissues to immunocompromised mice for long-term in vivo studies
• Fabrication of tissue platforms for pharmaceutical design and screening of drugs and small molecules in tissues at varying stages of cancer progression

Chemical and genetic modification of 3D tissues to identify and/or validate cellular targets

• Pharmacological manipulation of epithelial and/or mesenchymal cells in 3D tissues to test the effect of potentially-therapeutic bioactive compounds on cancer progression in these tissues
• Genetic manipulation of epithelial and/or mesenchymal cells in 3D tissues to modulate the expression or function of specific gene targets and to interrogate specific cancer-associated signaling pathways

Pharmacological manipulation of epithelial and/or mesenchymal cells in 3D tissues to test the effect of potentially-therapeutic bioactive compounds on cancer progression in these tissues

Screening potential cancer therapeutics and lead compounds for efficacy, safety and toxicity to accelerate the drug discovery in 3D tissue models that are predictive of human tissue response

• Screening and efficacy testing of novel candidate compounds that may have therapeutic potential in the treatment of human cancers in 3D tissues that will provide more reliable correlations between cell-based monolayer culture findings and in vivo outcomes in humans
• Validation of potential therapeutic targets identified in genomic/proteomic screens from either human clinical samples or from rudimentary 2D culture systems in engineered 3D tissues

Processing, Staining, Imaging, and Gene expression analysis of 3D engineered tissues

• Morphologic analysis of tissue architecture by Hematoxylin and Eosin staining
• Immunohistochemistry and immunofluorescence analysis of the expression and localization of target proteins in 3D tissues
• Tissue preparation for gene expression profiling as well as molecular and biochemical analysis
• Advanced optical imaging techniques are currently being developed and will shortly provide real time imaging capabilities in 3D tissues

Pricing will be determined on a case-by-case basis based on the scope of project and the tissue types involved.

What is the process to use the facility?

Please contact Dr. Addy Alt-Holland at 617-636-4072 to set up a meeting to discuss the specifics of the project you are interested in pursuing. At that time, a project plan will be designed and a budget generated to meet the needs of the specific application. You can also e-mail her at addy.alt_holland@tufts.edu to set up a meeting.

How should samples be prepared and delivered?

Culture or pellets of the cells of interest should be delivered to the Tissue Engineering Core with the medium and supplements that are needed for their growth and maintenance.

How long does it take from the time my cells are delivered until I can pick them up in the format of a 3D tissue?

Fabrication of engineered tissues usually requires three to four weeks, but this may vary with the cell type and scaffolds used. Tissue processing for histological analysis will take an additional seven days. For special stains, an additional seven to 10 days may be required.

How do I get my results?

After completion of the research work, Dr. Alt-Holland will prepare a final report recapitulating all the project findings and the interpretation of histologic findings. This will include captured images of all the stains that were performed.

Is all tissue processing done through the Tissue Engineering Core facility?

Yes, all tissue processing is performed in-house with the Core’s histology facilities in order to maintain high-quality of tissue analysis. The Tissue Engineering Core’s in-house processing and sectioning facilities ensures “one-stop shopping” for all tissue fabrication and analysis in an efficient and timely manner.

What is done with the tissue samples after the project has been completed?

All samples are returned to the investigator as blocks of formalin-fixed, paraffin-embedded tissues as well as sucrose-fixed, O.C.T. embedded tissues.

Can I learn techniques that will allow me to perform tissue fabrication in my own lab?

Fabrication of 3D tissue cultures is an extremely complex and multi-step process. Our expertise and experience allows it to optimize and streamline the fabrication, growth, processing and analysis of these tissues. For this reason, you are welcome to observe the fabrication and processing techniques. More active participation should be discussed with Dr. Garlick on a case-by-case basis.

Are there any cells or tissue types that would not be amenable to incorporation into 3D tissues?

No, we are able to fabricate a very broad range of 3D tissues and incorporate any cancer cell type into our 3D tissue constructs.

Can the Tissue Engineering Core perform genetic modification of cells to customize them before incorporation into 3D tissues?

Yes, we have extensive, in-house experience using viral vector systems for over-expressing or knocking down target genes. This includes cell manipulation by dominant negative strategies as well as shRNA and siRNA strategies. Bring your cells to our facility we will customize them for your experimental needs.

Addy Alt-Holland, PhD, Director

Tissue Engineering Core
55 Kneeland Street
Boston, MA 02111
Dr. Addy Alt-Holland
Phone: 617-636-4072
Fax: 617-636-6885
addy.alt_holland@tufts.edu