PMID- 35255978 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20220324 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 13 IP - 1 DP - 2022 Mar 7 TI - Human umbilical cord mesenchymal stem cell promotes angiogenesis via integrin beta1/ERK1/2/HIF-1alpha/VEGF-A signaling pathway for off-the-shelf breast tissue engineering. PG - 99 LID - 10.1186/s13287-022-02770-x [doi] LID - 99 AB - BACKGROUND: Mesenchymal stem cells (MSC)-based tissue engineered breast represent the visible future for breast reconstruction after mastectomy. However, autologous MSCs might not be appropriate for the large graft construction due to cell senescence during excessive cell expansion, thus hindering its further off-the-shelf application. The human umbilical cord mesenchymal stem cells (hUCMSCs) have been found to induce low immune response and can be easily stored, making them ideal for off-the-shelf tissue engineering application. Here, we explored the feasibility of using umbilical cord mesenchymal stem cells as tissue-engineered breast seed cells. METHODS: The allogenic hUCMSCs were injected into transplanted fat tissue with or without breast scaffolds as an alternative for breast tissue engineering in vivo, and its potential mechanism of angiogenesis in vitro was explored. RESULTS: Transplantation of hUCMSCs promoted proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) through paracrine mechanism by activating the integrin beta1/ERK1/2/HIF-1alpha/VEGF-A signaling pathway. Histological examination of grafted fat revealed that the group which received hUCMSCs transplantation had more fat tissue [(93.60 +/- 2.40) %] and fewer MAC2(+)CD206(-) M1 macrophages [(0.50 +/- 0.47) cells/field] compared to the control group [fat tissue (45.42 +/- 5.96) and macrophage cells/field (5.00 +/- 2.23)]. Moreover, the hUCMSCs- labeled with a tracing dye differentiated into adipocytes and vascular endothelial cells in the adipose tissue. When applied to the tissue-engineered breast with a scaffold, the group treated with hUCMSCs had more adipose tissues and CD31(+) cells than the control group. CONCLUSIONS: These results demonstrate that allogeneic hUCMSCs promote the regeneration of adipose tissue and can be used to construct a tissue engineered breast. CI - (c) 2022. The Author(s). FAU - Wu, Mian AU - Wu M AD - Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. AD - Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People's Republic of China. FAU - Chen, Lifeng AU - Chen L AD - Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. AD - Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People's Republic of China. FAU - Qi, Yuhan AU - Qi Y AD - Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. FAU - Ci, Hai AU - Ci H AD - Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. AD - Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People's Republic of China. FAU - Mou, Shan AU - Mou S AD - Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. AD - Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People's Republic of China. FAU - Yang, Jie AU - Yang J AD - Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. AD - Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People's Republic of China. FAU - Yuan, Qiaoyu AU - Yuan Q AD - Wuhan Optics Valley Zhongyuan Concord Cell Gene Technology Co., Ltd, Wuhan, People's Republic of China. FAU - Yao, Weiqi AU - Yao W AD - National Industrial Base for Stem Cell Engineering Products, Tianjin, People's Republic of China. AD - Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People's Republic of China. FAU - Wang, Zhenxing AU - Wang Z AUID- ORCID: 0000-0002-2436-0372 AD - Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. benjamin.wzx@163.com. AD - Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People's Republic of China. benjamin.wzx@163.com. FAU - Sun, Jiaming AU - Sun J AD - Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. sunjm1592@sina.com. AD - Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People's Republic of China. sunjm1592@sina.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220307 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (Integrin beta1) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - *Breast Neoplasms/metabolism MH - Female MH - Human Umbilical Vein Endothelial Cells/metabolism MH - Humans MH - Integrin beta1/genetics/metabolism MH - MAP Kinase Signaling System MH - Mastectomy MH - *Mesenchymal Stem Cells/metabolism MH - Signal Transduction MH - Tissue Engineering MH - Umbilical Cord/metabolism MH - Vascular Endothelial Growth Factor A/metabolism PMC - PMC8900416 OTO - NOTNLM OT - Angiogenesis OT - Mesenchymal stem cells OT - Tissue engineering OT - Umbilical cord COIS- The authors declared that they have no conflicts of interest to this work. EDAT- 2022/03/09 06:00 MHDA- 2022/03/25 06:00 PMCR- 2022/03/07 CRDT- 2022/03/08 05:33 PHST- 2021/10/12 00:00 [received] PHST- 2022/01/24 00:00 [accepted] PHST- 2022/03/08 05:33 [entrez] PHST- 2022/03/09 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2022/03/07 00:00 [pmc-release] AID - 10.1186/s13287-022-02770-x [pii] AID - 2770 [pii] AID - 10.1186/s13287-022-02770-x [doi] PST - epublish SO - Stem Cell Res Ther. 2022 Mar 7;13(1):99. doi: 10.1186/s13287-022-02770-x.