Organotypic culture as a research and preclinical model to study uterine leiomyomas

Sci Rep. 2020 Mar 23;10(1):5212. doi: 10.1038/s41598-020-62158-w.

Abstract

Organotypic cultures of tissue slices have been successfully established in lung, prostate, colon, gastric and breast cancer among other malignancies, but until now an ex vivo model based on tissue slices has not been established for uterine leiomyoma. In the present study, we describe a method for culturing tumour slides onto an alginate scaffold. Morphological integrity of tissue slices was maintained for up to 7 days of culture, with cells expressing desmin, estrogen and progesterone receptors. Driver mutations were present in the ex vivo slices at all-time points analyzed. Cultivated tumour slices responded to ovarian hormones stimulation upregulating the expression of genes involved in leiomyoma pathogenesis. This tissue model preserves extracellular matrix, cellular diversity and genetic background simulating more in-vivo-like situations. As a novelty, this platform allows encapsulation of microspheres containing drugs that can be tested on the ex vivo tumour slices. After optimizing drug release rates, microspheres would then be directly tested in animal models through local injection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates
  • Animals
  • Antineoplastic Agents / pharmacology
  • DNA Mutational Analysis
  • Drug Compounding
  • Drug Screening Assays, Antitumor
  • Estradiol* / pharmacology
  • Exons / genetics
  • Extracellular Matrix
  • Female
  • Leiomyoma / drug therapy
  • Leiomyoma / genetics
  • Leiomyoma / metabolism
  • Leiomyoma / pathology*
  • Mediator Complex / genetics
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology
  • Progesterone* / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Tissue Culture Techniques*
  • Tissue Scaffolds
  • Uterine Neoplasms / drug therapy
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology*

Substances

  • Alginates
  • Antineoplastic Agents
  • MED12 protein, human
  • Mediator Complex
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Progesterone
  • Estradiol