A Senomorphic-Conjugated Scaffold for Application of Senescent Cells in Regenerative Medicine

Procuring a sufficient amount of cells is essential for cell-based regenerative therapy. However, the application of senescent cells replicated using cell culture is limited because the cells have lost their regenerative ability or produce deleterious senescence-associated secretory phenotypes (SASPs). In this study, using a senomorphic (epigallocatechin gallate [EGCG]), which could modulate SASP secretion from senescent cells, nonsenescent and senescent dedifferentiated fat cells from rats (rDFAT cells), and congenital cleft-jaw defects in rats, the authors show that the senomorphic (EGCG)-conjugated cellular scaffold restores the bone regenerative ability of senescent multipotent progenitor cells, even in vivo. In this osteogenic process, the EGCG-conjugated scaffold attenuates the production of representative SASPs (i.e., interleukin [IL]-6 and tumor necrosis factor-alpha) and reactive oxygen species in vivo and in vitro. In polymerase chain reaction arrays in vitro, the EGCG-conjugated cellular scaffold suppresses the expression of genes associated with deleterious SASP factors for bone formation (e.g., Csf2, IL-1a, and others) from senescent rDFAT cells and elevates the expression of potential osteogenesis- and bone remodeling- related gene (e.g., Cxcl13 and Spp1). These results provide insights to expand the application of senomorphics and senescent stem/multipotent progenitor cells in cell-based regenerative medicine.