Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells
Abstract Background Smooth muscle progenitor cells (pSMCs) differentiated from human pluripotent stem cells (hPSCs) hold great promise for treating diseases or degenerative conditions involving smooth muscle pathologies. However, the therapeutic potential of pSMCs derived from men and women may be v...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-017-0606-2 |
| _version_ | 1818584368219684864 |
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| author | Yanhui Li Yan Wen Morgaine Green Elise K. Cabral Prachi Wani Fan Zhang Yi Wei Thomas M. Baer Bertha Chen |
| author_facet | Yanhui Li Yan Wen Morgaine Green Elise K. Cabral Prachi Wani Fan Zhang Yi Wei Thomas M. Baer Bertha Chen |
| author_sort | Yanhui Li |
| collection | DOAJ |
| description | Abstract Background Smooth muscle progenitor cells (pSMCs) differentiated from human pluripotent stem cells (hPSCs) hold great promise for treating diseases or degenerative conditions involving smooth muscle pathologies. However, the therapeutic potential of pSMCs derived from men and women may be very different. Cell sex can exert a profound impact on the differentiation process of stem cells into somatic cells. In spite of advances in translation of stem cell technologies, the role of cell sex and the effect of sex hormones on the differentiation towards mesenchymal lineage pSMCs remain largely unexplored. Methods Using a standard differentiation protocol, two human embryonic stem cell lines (one male line and one female line) and three induced pluripotent stem cell lines (one male line and two female lines) were differentiated into pSMCs. We examined differences in the differentiation of male and female hPSCs into pSMCs, and investigated the effect of 17β-estradiol (E2) on the extracellular matrix (ECM) metabolisms and cell proliferation rates of the pSMCs. Statistical analyses were performed by using Student’s t test or two-way ANOVA, p < 0.05. Results Male and female hPSCs had similar differentiation efficiencies and generated morphologically comparable pSMCs under a standard differentiation protocol, but the derived pSMCs showed sex differences in expression of ECM proteins, such as MMP-2 and TIMP-1, and cell proliferation rates. E2 treatment induced the expression of myogenic gene markers and suppressed ECM degradation activities through reduction of MMP activity and increased expression of TIMP-1 in female pSMCs, but not in male pSMCs. Conclusions hPSC-derived pSMCs from different sexes show differential expression of ECM proteins and proliferation rates. Estrogen appears to promote maturation and ECM protein expression in female pSMCs, but not in male pSMCs. These data suggest that intrinsic cell-sex differences may influence progenitor cell biology. |
| first_indexed | 2024-12-16T08:20:04Z |
| format | Article |
| id | doaj.art-630c20aca5044be093f3e02fe970d50b |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-16T08:20:04Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-630c20aca5044be093f3e02fe970d50b2022-12-21T22:38:09ZengBMCStem Cell Research & Therapy1757-65122017-07-018111610.1186/s13287-017-0606-2Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cellsYanhui Li0Yan Wen1Morgaine Green2Elise K. Cabral3Prachi Wani4Fan Zhang5Yi Wei6Thomas M. Baer7Bertha Chen8Department of Obstetrics/Gynecology, Stanford University School of MedicineDepartment of Obstetrics/Gynecology, Stanford University School of MedicineDepartment of Obstetrics/Gynecology, Stanford University School of MedicineDepartment of Obstetrics/Gynecology, Stanford University School of MedicineDepartment of Obstetrics/Gynecology, Stanford University School of MedicineDepartment of Obstetrics/Gynecology, Stanford University School of MedicineDepartment of Obstetrics/Gynecology, Stanford University School of MedicineStanford Photonics Research Center, Department of Applied Physics, Stanford UniversityDepartment of Obstetrics/Gynecology, Stanford University School of MedicineAbstract Background Smooth muscle progenitor cells (pSMCs) differentiated from human pluripotent stem cells (hPSCs) hold great promise for treating diseases or degenerative conditions involving smooth muscle pathologies. However, the therapeutic potential of pSMCs derived from men and women may be very different. Cell sex can exert a profound impact on the differentiation process of stem cells into somatic cells. In spite of advances in translation of stem cell technologies, the role of cell sex and the effect of sex hormones on the differentiation towards mesenchymal lineage pSMCs remain largely unexplored. Methods Using a standard differentiation protocol, two human embryonic stem cell lines (one male line and one female line) and three induced pluripotent stem cell lines (one male line and two female lines) were differentiated into pSMCs. We examined differences in the differentiation of male and female hPSCs into pSMCs, and investigated the effect of 17β-estradiol (E2) on the extracellular matrix (ECM) metabolisms and cell proliferation rates of the pSMCs. Statistical analyses were performed by using Student’s t test or two-way ANOVA, p < 0.05. Results Male and female hPSCs had similar differentiation efficiencies and generated morphologically comparable pSMCs under a standard differentiation protocol, but the derived pSMCs showed sex differences in expression of ECM proteins, such as MMP-2 and TIMP-1, and cell proliferation rates. E2 treatment induced the expression of myogenic gene markers and suppressed ECM degradation activities through reduction of MMP activity and increased expression of TIMP-1 in female pSMCs, but not in male pSMCs. Conclusions hPSC-derived pSMCs from different sexes show differential expression of ECM proteins and proliferation rates. Estrogen appears to promote maturation and ECM protein expression in female pSMCs, but not in male pSMCs. These data suggest that intrinsic cell-sex differences may influence progenitor cell biology.http://link.springer.com/article/10.1186/s13287-017-0606-2Sex differencesSmooth muscle progenitor cellPluripotent stem cellEstrogenExtracellular matrixCell proliferation |
| spellingShingle | Yanhui Li Yan Wen Morgaine Green Elise K. Cabral Prachi Wani Fan Zhang Yi Wei Thomas M. Baer Bertha Chen Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells Stem Cell Research & Therapy Sex differences Smooth muscle progenitor cell Pluripotent stem cell Estrogen Extracellular matrix Cell proliferation |
| title | Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells |
| title_full | Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells |
| title_fullStr | Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells |
| title_full_unstemmed | Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells |
| title_short | Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells |
| title_sort | cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells |
| topic | Sex differences Smooth muscle progenitor cell Pluripotent stem cell Estrogen Extracellular matrix Cell proliferation |
| url | http://link.springer.com/article/10.1186/s13287-017-0606-2 |
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