Table 1.

Cellular models: advantages and disadvantages.

Cell Culture Models	Advantages	Disadvantages
Primary microglial cultures	Study of the effect of genetic or toxic alterations associated with PD Controlled conditions, isolated effect	Does not replicate the complexity of the environment or the interaction with other cells of PD
IPSCs microglial-derived cells	Less invasive than primary cultures	It is unknown whether it replicates the phenotype of resident microglia
Culture of peripheral immune cells	The study of the phenotype of peripheral immune cells Transplantation from PD models to controls or vice versa (in vivo effects)	Require in vitro stimuli to induce cellular activation (e.g., LPS, oxidative stress, etc.)
Co-culture models:	They allow for the study of cellular interactions between CNS cells and IS cells under controlled conditions	The structural and environmental complexity is not replicated
Microglial + Astrocites + Neurons
Peripheral IS cells + Brain cells
IPSCs neurons + IS cells (microglial and macrophages)
Ex vivo brain slice cultures + immune cells	Better replicate structural complexity and can be co-cultured with immune cells to study their interaction	Does not allow for the study of long-term effects
Organoids	Mimic the complexity of brain and cellular interactions Reproduces the genetic background of the animal model or the patient	Does not contain some types of glial or immune cells, needs co-culture with them Requires a long time for proper organoid maturation