# Synthetic Cell‐Based Tissues for Bottom‐Up Assembly of Artificial Lymphatic Organs

## TL;DR

Researchers created synthetic cell-based tissues that mimic lymphatic organs and support immune cell integration and activation.

## Contribution

The study introduces self-assembling synthetic cells that form 3D lymphatic tissues capable of integrating with human immune cells.

## Key findings

- Synthetic cells self-assemble into 3D lymphatic tissues with mechanical adaptability and metabolic activity.
- Primary human immune cells infiltrate and functionally integrate into synthetic lymphatic tissues.
- Structured 3D organization of synthetic tissues enhances T cell activation and enables ex vivo expansion of regulatory CD8+ T cells.

## Abstract

Synthetic cells have emerged as a novel biomimetic approach for studying fundamental cellular functions and enabling new therapeutic interventions. However, the potential to program synthetic cells into self‐organized 3D collectives to replicate the structure and function of tissues has remained largely untapped. Here, self‐assembly properties are engineered into synthetic cells to form millimeter‐sized 3D lymphatic bottom‐up tissues (lymphBUTs) with mechanical adaptability, metabolic activity, and hierarchical microstructural organization. It is demonstrated that primary human immune cells spontaneously infiltrate and functionally integrate into these synthetic lymph nodes to form living tissue hybrids. Applying lymphBUTs, it is shown that structured 3D organization and mechanical support drives T cell activation and the application of lymphBUTs for ex vivo expansion of regulatory CD8+ T cells is demonstrated. The study highlights the functional integration of living and non‐living matter, advancing synthetic cell engineering toward 3D tissue structures.

Synthetic cells have emerged as a novel biomimetic approach for fundamental research and therapeutic interventions. T cell activating synthetic cells are able to form 3D tissue‐like structures by self‐assembly into lymphatic bottom‐up tissues (lymphBUT) with tunable biochemical and biomechanical functionalities as well as metabolic activity are presented. Synthetic cells and human T cells can functionally integrate and form living tissue hybrids.