PMID- 33318310 OWN - NLM STAT- MEDLINE DCOM- 20210510 LR - 20210510 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 13 IP - 2 DP - 2020 Dec 9 TI - Matrix stiffness regulates myocardial differentiation of human umbilical cord mesenchymal stem cells. PG - 2231-2250 LID - 10.18632/aging.202244 [doi] AB - Myocardial infarction is a cardiovascular disease with high mortality. Human umbilical cord mesenchymal stem cells (hUC-MSCs) with strong self-renewal capacity and multipotency, provide the possibility of replacing injured cardiomyocytes. hUC-MSCs were cultured on polyacrylamide hydrogels with stiffnesses corresponding to Young's modulus of 13-16kPa and 62-68kPa which mimic the stiffnesses of healthy heart tissue and fibrotic myocardium. The expression of early myocardial markers Nkx2.5, GATA4, Mesp1 and the mature myocardial markers cTnT, cTnI, alpha-actin were detected by RT-PCR and Western Blot, which showed that soft matrix (13-16 kPa) tended to induce the differentiation of hUC-MSCs into myocardium, compared with stiff matrix (62-68 kPa). Piezos are mechanically sensitive non-selective cation channels. The expression of Piezo1 increased with the stiffness gradient of 1-10kPa, 13-16kPa, 35-38kPa and 62-68kPa on the 1(st) day, but Piezo2 expression was irregular. The expression of integrin beta1 and calcium ions were also higher on stiff substrate than on soft substrate. hUC-MSCs tend to differentiate into myocardium on the matrix stiffness of 13-16 kPa. The relationship among matrix stiffness, Piezo1 and myocardial differentiation needs further validation. FAU - Sun, Yingying AU - Sun Y AD - Department of Stomatology, The First Hospital of Jilin University, Jilin University, Changchun, China. AD - The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China. FAU - Liu, Jingwei AU - Liu J AD - College of Clinical Medicine, Jilin University, Changchun, China. FAU - Xu, Ziran AU - Xu Z AD - The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China. FAU - Lin, Xiaoxuan AU - Lin X AD - The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China. FAU - Zhang, Xiaoling AU - Zhang X AD - Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital, Jilin University, Changchun, China. AD - National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China. FAU - Li, Lisha AU - Li L AD - The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China. FAU - Li, Yulin AU - Li Y AD - The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201209 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (Hydrogels) SB - IM MH - Cell Differentiation/*physiology MH - Cells, Cultured MH - Elastic Modulus MH - Extracellular Matrix/*metabolism MH - Female MH - Humans MH - Hydrogels MH - Mesenchymal Stem Cells/*cytology/metabolism MH - Myocardial Infarction/metabolism MH - Myocardium/*cytology/metabolism MH - Myocytes, Cardiac/*metabolism MH - Umbilical Cord/*cytology/metabolism PMC - PMC7880396 OTO - NOTNLM OT - Piezo1 OT - human umbilical cord mesenchymal stem cells OT - integrin beta1 OT - matrix stiffness OT - myocardial differentiation COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest. EDAT- 2020/12/16 06:00 MHDA- 2021/05/11 06:00 PMCR- 2021/01/31 CRDT- 2020/12/15 05:55 PHST- 2020/04/30 00:00 [received] PHST- 2020/10/20 00:00 [accepted] PHST- 2020/12/16 06:00 [pubmed] PHST- 2021/05/11 06:00 [medline] PHST- 2020/12/15 05:55 [entrez] PHST- 2021/01/31 00:00 [pmc-release] AID - 202244 [pii] AID - 10.18632/aging.202244 [doi] PST - ppublish SO - Aging (Albany NY). 2020 Dec 9;13(2):2231-2250. doi: 10.18632/aging.202244. Epub 2020 Dec 9.