Tissue Engineering

The In Vitro Systems/Tissue Engineering Program

Space-age methods of advanced tissue culture for cell interaction studies in normal and tumor tissue is leading to new ideas in the development of organ regeneration technology and improvement in cancer therapies.

The In Vitro Systems/Tissue Engineering program employs established and emerging cell and tissue culture methods for both in-house and collaborative research in medically significant areas. Previous work included design of clinical trials of implantation immunotherapy and production of stimulated autologous immune cells used to treat patients with recurrent malignant brain tumors or cancer of the urinary bladder.

Current emphasis is on the generation of realistic human tumor models that contain both stromal fibroblasts and malignant epithelial cells or stromal, epithelial and endothelial cells. The cells interact spontaneously under special culture conditions to form three-dimensional structures that have a remarkably tissue-like architecture. Because they are so like tissue, we refer to them as “histoids.” Each histoid particle is a few tenths of a millimeter in diameter. They can be reproducibly generated in multiple batches each of which contains hundreds of histoid particles. It was recently shown that individual histoid particles can be analyzed by flow cytometry and sorted into receptacles such as multiwell plates. The HMRI histoid bioreactor, designed in-house, is used in producing histoids.

 

Tumor histoids containing (a) prostate cancer and (b) pancreatic cancer cells. Fibroblast cores have been invaded by the cancer cells (dark stain) to produce the tissue-like architecture.

Potential uses of histoids include but are not limited to:

  • experimental studies of cell-cell interactions in realistic tumor models
  • invasive properties of cells
  • pre-screening anti-solid tumor pharmaceutical agents
  • use as reference specimens for immunostaining in the surgical pathology laboratory
  • histoids containing non-malignant cells as “seeds” in various tissue engineering applications