Design and development of in-vitro co-culture device for studying cellular crosstalk in varied tissue microenvironment

Biomater Adv. 2024 Oct:163:213952. doi: 10.1016/j.bioadv.2024.213952. Epub 2024 Jul 5.

Abstract

Despite of being in different microenvironment, breast cancer cells influence the bone cells and persuade cancer metastasis from breast to bone. Multiple co-culture approaches have been explored to study paracrine signaling between these cells and to study the progression of cancer. However, lack of native tissue microenvironment remains a major bottleneck in existing co-culture technologies. Therefore, in the present study, a tumorigenic and an osteogenic microenvironment have been sutured together to create a multi-cellular environment and has been appraised to study cancer progression in bone tissue. The PCL-polystyrene and PCL-collagen fibrous scaffolds were characterized for tumorigenic and osteogenic potential induction on MDA-MB-231 and MC3T3-E1 cells respectively. Diffusion ability of crystal violet, glucose, and bovine serum albumin across the membrane were used to access the potential paracrine interaction facilitated by device. While in co-cultured condition, MDA-MB-231 cells showed EMT phenotype along with secretion of TNFα and PTHrP which lower down the expression of osteogenic markers including alkaline phosphatase, RUNX2, Osteocalcin and Osteoprotegerin. The cancer progression in bone microenvironment demonstrated the role and necessity of creating multiple tissue microenvironment and its contribution in studying multicellular disease progression and therapeutics.

Keywords: Cancer; Co-culture; Nanofiber; Osteogenesis; Scaffold.

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cellular Microenvironment / physiology
  • Coculture Techniques*
  • Female
  • Humans
  • Mice
  • Osteogenesis* / physiology
  • Paracrine Communication
  • Parathyroid Hormone-Related Protein / metabolism
  • Tissue Scaffolds / chemistry
  • Tumor Microenvironment / physiology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Parathyroid Hormone-Related Protein