Microfluidic assembly of hydrogel-based immunogenic tumor spheroids for evaluation of anticancer therapies and biomarker release

Pooja Sabhachandani, Saheli Sarkar, Seamus Mckenney, Dashnamoorthy Ravi, Andrew M. Evens, Tania Konry

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Diffuse large B cell lymphoma (DLBCL), the most common subtype of Non-Hodgkin lymphoma, exhibits pathologic heterogeneity and a dynamic immunogenic tumor microenvironment (TME). However, the lack of preclinical in vitro models of DLBCL TME hinders optimal therapeutic screening. This study describes the development of an integrated droplet microfluidics-based platform for high-throughput generation of immunogenic DLBCL spheroids. The spheroids consist of three cell types (cancer, fibroblast and lymphocytes) in a novel hydrogel combination of alginate and puramatrix, which promoted cell adhesion and aggregation. This system facilitates dynamic analysis of cellular interaction, proliferation and therapeutic efficacy via spatiotemporal monitoring and secretome profiling. The immunomodulatory drug lenalidomide had direct anti-proliferative effect on activated B-cell like DLBCL spheroids and reduced several cytokines and other markers (e.g., CCL2, CCL3, CCL4, CD137 and ANG-1 levels) compared with untreated spheroids. Collectively, this novel spheroid platform will enable high-throughput anti-cancer therapeutic screening in a semi-automated manner.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalJournal of Controlled Release
Volume295
DOIs
StatePublished - Feb 10 2019

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • 3D culture
  • Alginate
  • Immunogenic spheroid
  • Microfluidics
  • Puramatrix

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