Mesenchymal Stromal Cells Isolated from Irradiated Human Skin Have Diminished Capacity for Proliferation, Differentiation, Colony Formation, and Paracrine Stimulation

Abstract

Ionizing radiation, commonly used in the treatment of solid tumors, has unintended but deleterious effects on overlying skin and is associated with chronic nonhealing wounds. Skin‐derived mesenchymal stromal cells (SMSCs) are a pluripotent population of cells that are critically involved in skin homeostasis and wound healing. The aim of this study was to isolate and functionally characterize SMSCs from human skin that was previously irradiated as part of neoadjuvant or adjuvant cancer therapy. To this end, SMSCs were isolated from paired irradiated and nonirradiated human skin samples. Irradiated SMSCs expressed characteristic SMSC markers at lower levels, had disorganized cytoskeletal structure, and had disordered morphology. Functionally, these cells had diminished proliferative capacity and substantial defects in colony‐forming capacity and differentiation in vitro. These changes were associated with significant differential expression of genes known to be involved in skin physiology and wound healing. Conditioned media obtained from irradiated SMSCs affected fibroblast but not endothelial cell proliferation and migration. These results suggest that in situ damage to SMSCs during neoadjuvant or adjuvant radiation may play a critical role in the pathogenesis of slow or nonhealing radiation wounds. stem cells translational medicine 2019;8:925&934

Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems

“…The multipotency of MSCs are dysregulated after TBI, in which a preferable differentiation toward adipocytes, along with an imbalanced activation between osteogenic and osteoclastic differentiation, occurs in BM [ 7 ]. TBI diminishes proliferation of osteoblastic progenitor cells with cell cycle arrest, and decreases the production of bone-consisting components [ 29 ]. ROS accumulation and subsequent oxidative stress are also closely associated with osteoclastogenesis, skeletal aging, and bone diseases [ 30 ].…”

Therapeutic Potential of Mesenchymal Stromal Cells and Extracellular Vesicles in the Treatment of Radiation Lesions—A Review

“…Like other cells, irradiation of MSCs induces senescence and/or apoptosis [ 49 ]. This has been shown in MSCs isolated from irradiated human skin, where colony formation, proliferation, and differentiation capacity are reduced [ 50 ].…”

Synergistic Effects of Icariin and Extracellular Vesicles Derived from Rabbit Synovial Membrane‐Derived Mesenchymal Stem Cells on Osteochondral Repair via the Wnt/β‐Catenin Pathway

“…Recently, synovial-derived MSCs (SMSCs) have been suggested as an alternative source of MSCs. SMSCs are not only highly pluripotent but are also independent of donor age, capable of passage to the 10th generation, and can be cryopreserved [ 16 , 17 , 18 , 19 , 20 ]. SMSCs also have a superior chondrogenic capability when compared with bone marrow MSCs (BM-MSCs) [ 21 ].…”