Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process
Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) are a promising cell source for bone tissue engineering. However, iMSCs have less osteogenic potential than BMSCs, and the classical iPSC-EB-iMSC process to derive iMSCs from iPSCs is too laborious as it involves multiple in...
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| Format: | Article |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.841778/full |
| _version_ | 1828365544073461760 |
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| author | Ziyi Hua Shuang Li Qianzi Liu Minxuan Yu Mengling Liao Hongmei Zhang Xuerong Xiang Qingqing Wu |
| author_facet | Ziyi Hua Shuang Li Qianzi Liu Minxuan Yu Mengling Liao Hongmei Zhang Xuerong Xiang Qingqing Wu |
| author_sort | Ziyi Hua |
| collection | DOAJ |
| description | Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) are a promising cell source for bone tissue engineering. However, iMSCs have less osteogenic potential than BMSCs, and the classical iPSC-EB-iMSC process to derive iMSCs from iPSCs is too laborious as it involves multiple in vitro steps. Low-intensity pulsed ultrasound (LIPUS) is a safe therapeutic modality used to promote osteogenic differentiation of stem cells. Whether LIPUS can facilitate osteogenic differentiation of iMSCs and simplify the iPSC-EB-iMSC process is unknown. We stimulated iMSCs with LIPUS at different output intensities (20, 40, and 60 mW/cm2) and duty cycles (20, 50, and 80%). Results of ALP activity assay, osteogenic gene expression, and mineralization quantification demonstrated that LIPUS was able to promote osteogenic differentiation of iMSCs, and it worked best at the intensity of 40 mW/cm2 and the duty cycle of 50% (LIPUS40/50). The Wnt/β-catenin signaling pathway was involved in LIPUS40/50-mediated osteogenesis. When cranial bone defects were implanted with iMSCs, LIPUS40/50 stimulation resulted in a significant higher new bone filling rate (72.63 ± 17.04)% than the non-stimulated ones (34.85 ± 4.53)%. Daily exposure to LIPUS40/50 may accelerate embryoid body (EB)–MSC transition, but it failed to drive iPSCs or EB cells to an osteogenic lineage directly. This study is the first to demonstrate the pro-osteogenic effect of LIPUS on iMSCs. Although LIPUS40/50 failed to simplify the classical iPSC-EB-MSC differentiation process, our preliminary results suggest that LIPUS with a more suitable parameter set may achieve the goal. LIPUS is a promising method to establish an efficient model for iPSC application. |
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| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-14T05:33:32Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-16d33ac96946415db54ea1edbfa988fd2022-12-22T02:09:44ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-05-011010.3389/fbioe.2022.841778841778Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation ProcessZiyi HuaShuang LiQianzi LiuMinxuan YuMengling LiaoHongmei ZhangXuerong XiangQingqing WuInduced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) are a promising cell source for bone tissue engineering. However, iMSCs have less osteogenic potential than BMSCs, and the classical iPSC-EB-iMSC process to derive iMSCs from iPSCs is too laborious as it involves multiple in vitro steps. Low-intensity pulsed ultrasound (LIPUS) is a safe therapeutic modality used to promote osteogenic differentiation of stem cells. Whether LIPUS can facilitate osteogenic differentiation of iMSCs and simplify the iPSC-EB-iMSC process is unknown. We stimulated iMSCs with LIPUS at different output intensities (20, 40, and 60 mW/cm2) and duty cycles (20, 50, and 80%). Results of ALP activity assay, osteogenic gene expression, and mineralization quantification demonstrated that LIPUS was able to promote osteogenic differentiation of iMSCs, and it worked best at the intensity of 40 mW/cm2 and the duty cycle of 50% (LIPUS40/50). The Wnt/β-catenin signaling pathway was involved in LIPUS40/50-mediated osteogenesis. When cranial bone defects were implanted with iMSCs, LIPUS40/50 stimulation resulted in a significant higher new bone filling rate (72.63 ± 17.04)% than the non-stimulated ones (34.85 ± 4.53)%. Daily exposure to LIPUS40/50 may accelerate embryoid body (EB)–MSC transition, but it failed to drive iPSCs or EB cells to an osteogenic lineage directly. This study is the first to demonstrate the pro-osteogenic effect of LIPUS on iMSCs. Although LIPUS40/50 failed to simplify the classical iPSC-EB-MSC differentiation process, our preliminary results suggest that LIPUS with a more suitable parameter set may achieve the goal. LIPUS is a promising method to establish an efficient model for iPSC application.https://www.frontiersin.org/articles/10.3389/fbioe.2022.841778/fullLIPUSiPSCsMSCsEBsosteogenic differentiation |
| spellingShingle | Ziyi Hua Shuang Li Qianzi Liu Minxuan Yu Mengling Liao Hongmei Zhang Xuerong Xiang Qingqing Wu Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process Frontiers in Bioengineering and Biotechnology LIPUS iPSCs MSCs EBs osteogenic differentiation |
| title | Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process |
| title_full | Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process |
| title_fullStr | Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process |
| title_full_unstemmed | Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process |
| title_short | Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process |
| title_sort | low intensity pulsed ultrasound promotes osteogenic potential of ipsc derived mscs but fails to simplify the ipsc eb msc differentiation process |
| topic | LIPUS iPSCs MSCs EBs osteogenic differentiation |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.841778/full |
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