An improved organotypic cell culture system to study tissue-resident macrophages ex vivo

Cell Rep Methods. 2022 Jul 26;2(8):100260. doi: 10.1016/j.crmeth.2022.100260. eCollection 2022 Aug 22.

Abstract

Tissue-resident macrophages (TRMs) perform organ-specific functions that are dependent on factors such as hematopoietic origin, local environment, and biological influences. A diverse range of in vitro culture systems have been developed to decipher TRM functions, including bone marrow-derived macrophages (BMDMs), induced pluripotent stem cell (iPSC)-derived TRMs, or immortalized cell lines. However, despite the usefulness of such systems, there are notable limitations. Attempts to culture primary macrophages often require purification of cells and lack a high cell yield and consistent phenotype. Here, we aimed to address these limitations by establishing an organotypic primary cell culture protocol. We obtained long-term monocultures of macrophages derived from distinct organs without prior purification using specific growth factors and tissue normoxic conditions that largely conserved a TRM-like identity in vitro. Thus, this organotypic system offers an ideal screening platform for primary macrophages from different organs that can be used for a wide range of assays and readouts.

Keywords: Kupffer cells; alveolar macrophages; bone marrow-derived macrophages; macrophages; microglia; organotypic cell culture; peritoneal macrophages; tissue normoxia; tissue-resident macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics
  • Histiocytes
  • Induced Pluripotent Stem Cells*
  • Macrophages
  • Microphysiological Systems*