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

Abstract

AbstractProcuring 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‐α) 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.