title: Sox10+adult stem cells contribute to biomaterial encapsulation and microvascularization.
abstract: Implanted biomaterials and biomedical devices generally induce foreign body reaction and end up with encapsulation by a dense avascular fibrous layer enriched in extracellular matrix. Fibroblasts/myofibroblasts are thought to be the major cell type involved in encapsulation, but it is unclear whether and how stem cells contribute to this process. Here we show, for the first time, that Sox10+adult stem cells contribute to both encapsulation and microvessel formation. Sox10+adult stem cells were found sparsely in the stroma of subcutaneous loose connective tissues. Upon subcutaneous biomaterial implantation, Sox10+stem cells were activated and recruited to the biomaterial scaffold, and differentiated into fibroblasts and then myofibroblasts. This differentiation process from Sox10+stem cells to myofibroblasts could be recapitulated in vitro. On the other hand, Sox10+stem cells could differentiate into perivascular cells to stabilize newly formed microvessels. Sox10+stem cells and endothelial cells in three-dimensional co-culture self-assembled into microvessels, and platelet-derived growth factor had chemotactic effect on Sox10+stem cells. Transplanted Sox10+stem cells differentiated into smooth muscle cells to stabilize functional microvessels. These findings demonstrate the critical role of adult stem cells in tissue remodeling and unravel the complexity of stem cell fate determination.
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|School of Optometry and Vision Science Program, University of California, Berkeley, California 94720, USA.|Department of Bioengineering, University of California, Los Angeles, California 90095, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|Department of Surgery, University of California, Davis, Sacramento, California 95817, USA.
authors.forename: Aijun
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|Department of Bioengineering, University of California, Los Angeles, California 90095, USA.|Department of Cardiovascular Surgery, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.|Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|Department of Bioengineering, University of California, Los Angeles, California 90095, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Xu
authors.affiliation: School of Optometry and Vision Science Program, University of California, Berkeley, California 94720, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California 94720, USA.|Department of Bioengineering, University of California, Los Angeles, California 90095, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000187:drug effects; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D055806:Microvessels / Q000254:growth & development* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D051381:Rats; D055757:SOXE Transcription Factors / Q000235:genetics*; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D055757:SOXE Transcription Factors; C527925:Sox10 protein, rat