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Stem Cells Transl Med. 2019 Apr 24. doi: 10.1002/sctm.18-0112. [Epub ahead of print]

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

Author information

1
Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA.
2
Department of Surgery, Keck School of Medicine of USC, Los Angeles, California, USA.
3
Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, California, USA.
4
Department of Biochemistry and Molecular Biology, Keck School of Medicine of USC, Los Angeles, California, USA.
5
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry of USC, Los Angeles, California, USA.
6
Center for Genomics, Loma Linda University, Loma Linda, California, USA.
7
Department of Dermatology, Keck School of Medicine of USC, Los Angeles, California, USA.

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.

KEYWORDS:

Differentiation; Human; Ionizing radiation; Mesenchymal; Migration; Proliferation; Radiotherapy; Skin; Stem cells; Stromal cell; Wound healing

PMID:
31020798
DOI:
10.1002/sctm.18-0112
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