Therapeutic Regeneration of Lymphatic and Immune Cell Functions upon Lympho-organoid Transplantation

Lymph nodes (LNs) are secondary lymphoid tissues that play a critical role in filtering the lymph and promoting adaptive immune responses. Surgical resection of LNs, radiation therapy, or infections may damage lymphatic vasculature and compromise immune functions. Here, we describe the generation of functional synthetic lympho-organoids (LOs) using LN stromal progenitors and decellularized extracellular matrix-based scaffolds, two basic constituents of secondary lymphoid tissues. We show that upon transplantation at the site of resected LNs, LOs become integrated into the endogenous lymphatic vasculature and efficiently restore lymphatic drainage and perfusion. Upon immunization, LOs support the activation of antigen-specific immune responses, thus acquiring properties of native lymphoid tissues. These findings provide a proof-of-concept strategy for the development of functional lympho-organoids suitable for restoring lymphatic and immune cell functions. In this article, Lenti and colleagues show the generation of functional lympho-organoids using basic constituents of the lymph node. Their findings indicate that transplantation of lympho-organoids may represent a therapeutic approach to restore lymphatic and immune cell functions in lymphedema and other diseases in which lymph nodes have been removed or are dysfunctional.