Research Advances in Multi-tissue Organoid Models Based on PBMCs

Organoids, as three-dimensional in vitro culture models, closely recapitulate the architectural, cellular, and functional characteristics of their in vivo counterparts. Consequently, they play a pivotal role in diverse biomedical fields, including disease modeling, drug screening, and regenerative medicine. However, conventional organoid models often lack a complex native microenvironment, specifically the tumor microenvironment (TME), which limits their utility in studying immune-related pathologies and evaluating immunotherapeutic strategies. Peripheral blood mononuclear cells (PBMCs) offer distinct advantages, including accessibility, a heterogeneous composition of immune cells, and the capacity to mirror a patient's specific immune status. As a result, PBMCs have emerged as a predominant source of immune cells for engineering immune-integrated organoid models. This article reviews recent advancements in integrating PBMCs into various tissue organoid systems. It summarizes the key biological properties of PBMCs and their applications across multiple models, including cerebral, renal, pulmonary, and hepatic organoids. Furthermore, this study compares the advantages and limitations of current modeling methodologies and discusses future research directions and persistent challenges in leveraging PBMC-integrated organoids for personalized medicine and the elucidation of disease mechanisms.