Table 4.

Benefits and limitation of microglial in vitro culture models

Culture model	Benefits	Limitations
Cultured primary microglia	Moderately easy to culture Susceptible to HIV infection	Difficult to obtain fresh human brain tissue Limited number of viable cells Limited life span Transcriptomic deficiencies induced by in vitro culture
Microglial cell lines	Commercially available Easy to culture Mass production Long-term culture Genetic modifications: HIV latency	Transcriptomic profile does not cluster with adult or fetal primary microglia Not susceptible to HIV infection
Monocyte-derived microglia	Easy to obtain and culture Mass production Susceptible to HIV infection	Limited life span Transcriptomic profile does not cluster with adult or fetal primary microglia Expensive
iPSC-derived microglia	Mass production Long-term culture Genetic modifications Susceptible to HIV infection	Transcriptomic profile clusters more closely with fetal microglia Technically complex and time consuming Very expensive
3D organoids	Recapitulate in vivo CNS structure Cell–cell interaction with other CNS cell types Microglia developed in a 3D microenvironment Transcriptomic profile cluster with adult primary microglia Long-term culture	High inter- and intra-variability between organoids Variability in differentiation protocols; patterned and non-patterned Technically complex and time consuming Lack vasculature Ethical concerns Very expensive