Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons
Abstract Background Phenotypically unstable Schwann cell-like cells (SCLCs), derived from mesenchymal stem cells (MSCs) require intercellular contact-mediated cues for Schwann cell (SCs)-fate commitment. Although rat dorsal root ganglion (DRG) neurons provide contact-mediated signals for the convers...
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BMC
2025-03-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04217-5 |
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| author | Yu Pan Haohui Lin Manhon Chung Yi Yang Li Zhang Xiaohua Pan Sa Cai |
| author_facet | Yu Pan Haohui Lin Manhon Chung Yi Yang Li Zhang Xiaohua Pan Sa Cai |
| author_sort | Yu Pan |
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| description | Abstract Background Phenotypically unstable Schwann cell-like cells (SCLCs), derived from mesenchymal stem cells (MSCs) require intercellular contact-mediated cues for Schwann cell (SCs)-fate commitment. Although rat dorsal root ganglion (DRG) neurons provide contact-mediated signals for the conversion of SCLCs into fate-committed SCs, the use of animal cells is clinically unacceptable. To overcome this problem, we previously acquired human induced pluripotent stem cell-derived sensory neurons (hiPSC-dSNs) as surrogates of rat DRG neurons that committed rat bone marrow SCLCs to the SC fate. In this study, we explored whether hiPSC-dSNs could mimic rat DRG neuron effects to obtain fate-committed SCs from hBMSC-derived SCLCs. Methods hiPSCs were induced into hiPSC-dSNs using a specific chemical small molecule combination. hBMSCs were induced into hBMSC-derived SCLCs in a specific culture medium and then co-cultured with hiPSC-dSNs to generate SCs. The identity of hBMSC-derived SCs (hBMSC-dSCs) was examined by immunofluorescence, western bolt, electronic microscopy, and RNA-seq. Immunofluorescence was also used to detect the myelination capacity. Enzyme-linked immunosorbent assay and neurite outgrowth analysis were used to test the secretion of neurotrophic factors. Results The hBMSC-dSCs exhibited bi-/tri-polar morphology of SCs and maintained the expression of the SC markers S100, p75NTR, p0, GFAP, and Sox10, even after withdrawing the glia-inducing factors or hiPSC-dSNs. Electronic microscopy and RNA-seq analysis provided evidence that hBMSC-dSCs were similar to the original human SCs in terms of their function and a variety of characteristics. Furthermore, these cells formed MBP-positive segments and secreted neurotrophic factors to facilitate the neurite outgrowth of Neuro2A. Conclusions These results demonstrated that phenotypically stable and functionally mature hBMSC-dSCs were generated efficiently via the co-culture of hiPSC-dSNs and hBMSC-derived SCLCs. Our findings may provide a promising protocol through which stable and fully developed hBMSC-dSCs can be used for transplantation to regenerate myelin sheath. Graphical abstract |
| format | Article |
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| spelling | doaj-art-dea5d2c704064ee09c6df04a8bbb06ca2025-08-20T02:16:54ZengBMCStem Cell Research & Therapy1757-65122025-03-0116111610.1186/s13287-025-04217-5Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neuronsYu Pan0Haohui Lin1Manhon Chung2Yi Yang3Li Zhang4Xiaohua Pan5Sa Cai6Laboratory of Regenerative Medicine, Medical School, The 2nd Affiliated Hospital of Shenzhen University, Shenzhen UniversityLaboratory of Regenerative Medicine, Medical School, The 2nd Affiliated Hospital of Shenzhen University, Shenzhen UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineLaboratory of Regenerative Medicine, Medical School, The 2nd Affiliated Hospital of Shenzhen University, Shenzhen UniversityLaboratory of Regenerative Medicine, Medical School, The 2nd Affiliated Hospital of Shenzhen University, Shenzhen UniversityLaboratory of Regenerative Medicine, Medical School, The 2nd Affiliated Hospital of Shenzhen University, Shenzhen UniversityLaboratory of Regenerative Medicine, Medical School, The 2nd Affiliated Hospital of Shenzhen University, Shenzhen UniversityAbstract Background Phenotypically unstable Schwann cell-like cells (SCLCs), derived from mesenchymal stem cells (MSCs) require intercellular contact-mediated cues for Schwann cell (SCs)-fate commitment. Although rat dorsal root ganglion (DRG) neurons provide contact-mediated signals for the conversion of SCLCs into fate-committed SCs, the use of animal cells is clinically unacceptable. To overcome this problem, we previously acquired human induced pluripotent stem cell-derived sensory neurons (hiPSC-dSNs) as surrogates of rat DRG neurons that committed rat bone marrow SCLCs to the SC fate. In this study, we explored whether hiPSC-dSNs could mimic rat DRG neuron effects to obtain fate-committed SCs from hBMSC-derived SCLCs. Methods hiPSCs were induced into hiPSC-dSNs using a specific chemical small molecule combination. hBMSCs were induced into hBMSC-derived SCLCs in a specific culture medium and then co-cultured with hiPSC-dSNs to generate SCs. The identity of hBMSC-derived SCs (hBMSC-dSCs) was examined by immunofluorescence, western bolt, electronic microscopy, and RNA-seq. Immunofluorescence was also used to detect the myelination capacity. Enzyme-linked immunosorbent assay and neurite outgrowth analysis were used to test the secretion of neurotrophic factors. Results The hBMSC-dSCs exhibited bi-/tri-polar morphology of SCs and maintained the expression of the SC markers S100, p75NTR, p0, GFAP, and Sox10, even after withdrawing the glia-inducing factors or hiPSC-dSNs. Electronic microscopy and RNA-seq analysis provided evidence that hBMSC-dSCs were similar to the original human SCs in terms of their function and a variety of characteristics. Furthermore, these cells formed MBP-positive segments and secreted neurotrophic factors to facilitate the neurite outgrowth of Neuro2A. Conclusions These results demonstrated that phenotypically stable and functionally mature hBMSC-dSCs were generated efficiently via the co-culture of hiPSC-dSNs and hBMSC-derived SCLCs. Our findings may provide a promising protocol through which stable and fully developed hBMSC-dSCs can be used for transplantation to regenerate myelin sheath. Graphical abstracthttps://doi.org/10.1186/s13287-025-04217-5Human induced pluripotent stem cellsHuman bone marrow mesenchymal stem cellsSensory neuronsFate commitmentSchwann cellsMyelination |
| spellingShingle | Yu Pan Haohui Lin Manhon Chung Yi Yang Li Zhang Xiaohua Pan Sa Cai Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons Stem Cell Research & Therapy Human induced pluripotent stem cells Human bone marrow mesenchymal stem cells Sensory neurons Fate commitment Schwann cells Myelination |
| title | Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons |
| title_full | Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons |
| title_fullStr | Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons |
| title_full_unstemmed | Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons |
| title_short | Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons |
| title_sort | generation of phenotypically stable and functionally mature human bone marrow mscs derived schwann cells via the induction of human ipscs derived sensory neurons |
| topic | Human induced pluripotent stem cells Human bone marrow mesenchymal stem cells Sensory neurons Fate commitment Schwann cells Myelination |
| url | https://doi.org/10.1186/s13287-025-04217-5 |
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