Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis.
The cutaneous wound-healing process can lead to hypertrophic scar formation, during which exaggerated inflammation has been demonstrated to have an important role. Therefore, an exploration of strategies designed to regulate this inflammatory process is warranted. Mesenchymal stem cells (MSCs) have recently been demonstrated to regulate inflammation in various diseases. In this regard, using a rabbit model, we locally injected human mesenchymal stem cells (hMSCs) derived from bone marrow to treat hypertrophic scar formation, and explored their underlying mechanisms. We found that hMSC therapy efficiently regulated inflammation and prevented scar formation. We attributed the therapeutic effects of hMSCs to their secretion of an anti-inflammatory protein, TNF-alpha-stimulated gene/protein 6 (TSG-6). Unexpectedly, after injection, the number of surviving hMSCs decreased markedly and the hMSCs underwent extensive apoptosis, which was demonstrated to promote their secretion of TSG-6, partially through the activation of caspase-3. Moreover, H2O2-induced apoptotic hMSCs showed higher inflammatory regulatory abilities. The inhibition of caspase-3 decreased the inflammatory regulatory abilities of hMSCs and attenuated their therapeutic effects. Our results demonstrate that hMSCs can efficiently prevent hypertrophic scar formation via inflammatory regulation. In addition, we found that apoptosis has an important role in the activation of the inflammatory regulatory abilities of hMSCs.
Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China; These authors contributed equally to this work.
Shiyu
S
Liu
Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China; These authors contributed equally to this work.
Lan
L
Jiang
Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Haijian
H
Li
Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China.
Haigang
H
Shi
Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi, China.
Hailang
H
Luo
Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi, China.
Yongjie
Y
Zhang
Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: yucy2003@yahoo.com.cn.
Chunyan
C
Yu
Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: yanjinfmmu@vip.sina.com.
Yan
Y
Jin
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D023421:Models, Animal; D011817:Rabbits; D012867:Skin / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology
D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human; D053148:Caspase 3