Harnessing Mesenchymal Aggregation for Engineered Organ-Level Regeneration: Recent Progress and Perspective

The document reviews the principles and mechanisms of mesenchymal stem cell (MSC) aggregation and its application in organ-level regeneration. MSC aggregates, which naturally form spheroid-like assemblies, exhibit enhanced regenerative capacities, including differentiation, vascularization, and organogenesis. These engineered aggregates, termed "cytocondensoids," can integrate with host tissues and initiate regenerative processes, showing promise for organ replacement therapies. The review highlights the use of MSCs from various sources and the incorporation of biomaterials to enhance translational potential. Challenges include understanding the physiological mechanisms of aggregation, heterogeneity of MSCs, and integration behavior in vivo. Advances in single-cell and spatial multi-omics technologies are expected to optimize these regenerative techniques for clinical applications.