Journal of Zhejiang University SCIENCE B 2026 Vol.27 No.6 P.628-644

http://doi.org/10.1631/jzus.B2400611


Regenerative potential of Schneiderian membrane-derived mesenchymal stem cells in sinus floor elevation model and calvarial defect model


Author(s):  Yuxin ZHAO, Jia WANG, Dongqi YOU, Yifan LU, Mengfei YU, Misi SI

Affiliation(s):  1. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China

Corresponding email(s):   misi_si@zju.edu.cn, yumengfei@zju.edu.cn

Key Words:  Schneiderian membrane-derived mesenchymal stem cells (SMMSCs), Single-cell RNA sequencing, Osteogenesis, Maxillary sinus floor elevation (MSFE), Calvarial defect


Yuxin ZHAO, Jia WANG, Dongqi YOU, Yifan LU, Mengfei YU, Misi SI. Regenerative potential of Schneiderian membrane-derived mesenchymal stem cells in sinus floor elevation model and calvarial defect model[J]. Journal of Zhejiang University Science B, 2026, 27(6): 628-644.

@article{title="Regenerative potential of Schneiderian membrane-derived mesenchymal stem cells in sinus floor elevation model and calvarial defect model",
author="Yuxin ZHAO, Jia WANG, Dongqi YOU, Yifan LU, Mengfei YU, Misi SI",
journal="Journal of Zhejiang University Science B",
volume="27",
number="6",
pages="628-644",
year="2026",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2400611"
}

%0 Journal Article
%T Regenerative potential of Schneiderian membrane-derived mesenchymal stem cells in sinus floor elevation model and calvarial defect model
%A Yuxin ZHAO
%A Jia WANG
%A Dongqi YOU
%A Yifan LU
%A Mengfei YU
%A Misi SI
%J Journal of Zhejiang University SCIENCE B
%V 27
%N 6
%P 628-644
%@ 1673-1581
%D 2026
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2400611

TY - JOUR
T1 - Regenerative potential of Schneiderian membrane-derived mesenchymal stem cells in sinus floor elevation model and calvarial defect model
A1 - Yuxin ZHAO
A1 - Jia WANG
A1 - Dongqi YOU
A1 - Yifan LU
A1 - Mengfei YU
A1 - Misi SI
J0 - Journal of Zhejiang University Science B
VL - 27
IS - 6
SP - 628
EP - 644
%@ 1673-1581
Y1 - 2026
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2400611


Abstract: 
Objectivesschneiderian membrane-derived mesenchymal stem cells (SMMSCs) have been reported to be osteogenic progenitor cells in vitro. However, there is controversy regarding the intrinsic osteogenic capacity of the Schneiderian membrane, and the bone formation potential of SMMSCs in vivo has never been reported. Therefore, in this study, we aimed to evaluate the contribution of the Schneiderian membrane to sinus floor elevation and to verify the function of SMMSCs in cranial bone defects.
Materials and methodsBilateral sinus floor elevation with chloromethyl-benzamidodialkylcarbocyanine (CM-Dil) labeling was performed in rabbits to assess Schneiderian membrane osteogenesis. single-cell RNA sequencing was used to characterize human Schneiderian membrane cellular subsets. SMMSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were transplanted into rabbit cranial defects with gelatin methacryloyl (GelMA) scaffolds and analyzed via micro-computed tomography (micro-CT) and histology.
ResultsSpontaneous bone formation adjacent to the Schneiderian membrane was observed. Single-cell analysis identified paired-related homeobox 1 (PRRX1) progenitor clusters driving endosinus osteogenesis. SMMSCs exhibited earlier and superior bone regeneration compared with BMSCs, with higher tissue volume and bone volume/total volume (BV/TV) ratios at four weeks after surgery.
ConclusionsThe Schneiderian membrane likely contributes to osteogenesis via PRRX1+ progenitor lineages. SMMSCs promote accelerated early bone regeneration in cranial defects. This study provides the first in vivo validation of the osteogenic capacity of SMMSCs and defines their molecular identity at single-cell resolution.

施耐德膜来源间充质干细胞在上颌窦底提升模型与颅骨缺损模型中的再生潜能

赵雨馨, 王佳, 游东奇, 陆怡凡, 俞梦飞, 姒蜜思
浙江大学医学院附属口腔医院,浙江大学口腔医学院,浙江省口腔疾病临床医学研究中心, 浙江省口腔生物医学研究重点实验室,浙江大学癌症研究院,口腔生物材料与器械浙江省工程研究中心, 中国杭州, 310000
摘要:目的:施耐德膜来源间充质干细胞(SMMSCs)曾被报道具有体外成骨分化潜能,但其在体内的骨形成能力尚不明确。本研究旨在评估施耐德膜在上颌窦底提升中的成骨作用,并验证SMMSCs在颅骨缺损修复中的功能。材料与方法:通过兔双侧上颌窦底提升术结合氯甲基苯甲酰胺二烷基碳菁荧光素(CM-Dil)标记技术评估施耐德膜的原位成骨能力;利用单细胞RNA测序技术解析人施耐德膜的细胞亚群特征;将SMMSCs与骨髓间充质干细胞(BMSCs)联合明胶甲基丙烯酰(GelMA)支架移植于兔颅骨缺损区,通过显微CT与组织学分析评估骨再生效果。结果:上颌窦底提升模型中,施耐德膜邻近区域观察到自发性骨形成;单细胞测序分析鉴定出成对相关同源框1(PRRX1)阳性祖细胞群主导了窦腔内成骨过程;颅骨缺损模型中,SMMSCs较BMSCs在移植后4周表现出更显著的早期骨再生能力,展现出更高的骨体积分数(BV/TV)。结论:施耐德膜可能通过PRRX1+祖细胞谱系参与成骨调控;SMMSCs可加速颅骨缺损的早期修复。本研究首次在体内验证了SMMSCs的成骨潜能,并在单细胞分辨率下阐明其分子机制。

关键词:施耐德膜来源间充质干细胞(SMMSCs);单细胞RNA测序;骨再生;上颌窦底提升;颅骨缺损

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Al-DajaniM, 2016. Recent trends in sinus lift surgery and their clinical implications. Clin Implant Dent Relat Res, 18(1):204-212.

[2]AnkrumJA, OngJF, KarpJM, 2014. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol, 32(3):252-260.

[3]AsaiS, ShimizuY, OoyaK, 2002. Maxillary sinus augmentation model in rabbits: effect of occluded nasal ostium on new bone formation. Clin Oral Implants Res, 13(4):405-409.

[4]ChenJM, HuangQY, ZhaoYX, et al., 2021. The latest developments in immunomodulation of mesenchymal stem cells in the treatment of intrauterine adhesions, both allogeneic and autologous. Front Immunol, 12:785717.

[5]ChenPH, TsaiWB, 2025. Development of a photocrosslinkable collagen-bone matrix hydrogel for bone tissue engineering. Polymers, 17(7):935.

[6]de Carvalho Silva Leocádio A, SilvaM, deOliveira GJPL, et al., 2021. Osseointegration of different implant surfaces in areas grafted with deproteinized bovine bone associated or not with fresh bone marrow—preclinical study in rabbits. Clin Oral Implants Res, 32(6):767-775.

[7]DengQ, LiP, CheMJ, et al., 2019. Activation of hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt/β-Catenin. eLife, 8:e50208.

[8]Derjac-AramăAI, SarafoleanuC, ManeaCM, et al., 2015. Regenerative potential of human Schneiderian membrane: progenitor cells and epithelial-mesenchymal transition. Anat Rec, 298(12):2132-2140.

[9]di PietroL, BarbaM, PrampoliniC, et al., 2020. GLI1 and AXIN2 are distinctive markers of human calvarial mesenchymal stromal cells in nonsyndromic craniosynostosis. Int J Mol Sci, 21(12):4356.

[10]DragonasP, KatsarosT, SchiavoJ, et al., 2020. Osteogenic capacity of the sinus membrane following maxillary sinus augmentation procedures: a systematic review. Int J Oral Implantol, 13(3):213-232.

[11]FalahM, SohnDS, SroujiS, 2016. Graftless sinus augmentation with simultaneous dental implant placement: clinical results and biological perspectives. Int J Oral Maxillofac Surg, 45(9):1147-1153.

[12]FriedensteinAJ, ChailakhjanRK, LalykinaKS, 1970. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Proliferat, 3(4):393-403.

[13]FujiiS, TakebeH, MizoguchiT, et al., 2023. Bone formation ability of Gli1+ cells in the periodontal ligament after tooth extraction. Bone, 173:116786.

[14]GranchiD, DevescoviV, BaglioSR, et al., 2010. Biological basis for the use of autologous bone marrow stromal cells in the treatment of congenital pseudarthrosis of the tibia. Bone, 46(3):780-788.

[15]GuoJB, WengJQ, RongQ, et al., 2015. Investigation of multipotent postnatal stem cells from human maxillary sinus membrane. Sci Rep, 5:11660.

[16]HameedS, BakhshalianN, AlwazanE, et al., 2019. Maxillary sinus floor and alveolar crest alterations following extraction of single maxillary molars: a retrospective cbct analysis. Int J Periodontics Restorative Dent, 39(4):545-551.

[17]HuW, FeiTY, LiuZC, et al., 2025. Single-cell RNA-sequencing-guided reactive oxygen species-scavenging hydrogel design for regeneration of osteoporotic bone. J Zhejiang Univ-Sci B, 26(12):1172-1191.

[18]JungnerM, CricchioG, SalataLA, et al., 2015. On the early mechanisms of bone formation after maxillary sinus membrane elevation: an experimental histological and immunohistochemical study. Clin Implant Dent Relat Res, 17(6):1092-1102.

[19]LeeE, EpanomeritakisIE, LuV, et al., 2023. Bone marrow-derived mesenchymal stem cell implants for the treatment of focal chondral defects of the knee in animal models: a systematic review and meta-analysis. Int J Mol Sci, 24(4):3227.

[20]LeeJY, KimS, ShinSY, et al., 2022. Effectiveness of hydraulic pressure-assisted sinus augmentation in a rabbit sinus model: a preclinical study. Clin Oral Investig, 26(2):1581-1591.

[21]LemosDR, EisnerC, HopkinsCI, et al., 2015. Skeletal muscle-resident MSCs and bone formation. Bone, 80:19-23.

[22]LimST, KusanoK, TaniyamaT, et al., 2022. Contribution to bone formation of the Schneiderian membrane after sinus augmentation: a histological study in rabbits. Materials (Basel), 15(22):8077.

[23]LiuJQ, KangJ, ZouT, et al., 2025. Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis. J Nanobiotechnol, 23:179.

[24]LiuYN, WangHF, DouHX, et al., 2020. Bone regeneration capacities of alveolar bone mesenchymal stem cells sheet in rabbit calvarial bone defect. J Tissue Eng, 11:1-12.

[25]LvHX, XuJ, WangYH, et al., 2024. Isolation, identification and osteogenic capability analysis of mesenchymal stem cells derived from different layers of human maxillary sinus membrane. J Clin Periodontol, 51(6):754-765.

[26]MaZJ, JiaWD, WangXY, et al., 2025. Novel multi-component synergistic bioink that balances biocompatibility and mechanical strength for cartilage regeneration. J Zhejiang Univ-Sci B, 26(12):1156-1171.

[27]MakaryC, RebaudiA, MenhallA, et al., 2016. Changes in sinus membrane thickness after lateral sinus floor elevation: a radiographic study. Int J Oral Maxillofac Implants, 31(2):331-337.

[28]MaruyamaT, JiangM, AbbottA, et al., 2017. Rap1b is an effector of Axin2 regulating crosstalk of signaling pathways during skeletal development. J Bone Miner Res, 32(9):1816-1828.

[29]MaurerT, StoffelMH, BelyaevY, et al., 2018. Structural characterization of four different naturally occurring porcine collagen membranes suitable for medical applications. PLoS One, 13(10):e0205027.

[30]MoonYS, SohnDS, MoonJW, et al., 2014. Comparative histomorphometric analysis of maxillary sinus augmentation with absorbable collagen membrane and osteoinductive replaceable bony window in rabbits. Implant Dent, 23(1):29-36.

[31]PalmaVC, Magro-FilhoO, de OliveriaJA, et al., 2006. Bone reformation and implant integration following maxillary sinus membrane elevation: an experimental study in primates. Clin Implant Dent Relat Res, 8(1):11-24.

[32]PereiraRDS, deCarvalho MVNB, Hochuli-VieiraE, et al., 2024. Histomorphometric and micro-CT evaluation of cerabone and Bio-Oss in maxillary sinus lifting: a randomized clinical trial. Medicina, 60(11):1834.

[33]PjeturssonBE, LangNP, 2014. Sinus floor elevation utilizing the transalveolar approach. Periodontol 2000, 66(1):59-71.

[34]QianSJ, MoJJ, ShiJY, et al., 2018. Endo-sinus bone formation after transalveolar sinus floor elevation without grafting with simultaneous implant placement: histological and histomorphometric assessment in a dog model. J Clin Periodontol, 45(9):1118-1127.

[35]ReindersMEJ, de FijterJW, RoelofsH, et al., 2013. Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med, 2:107-111.

[36]RongQ, LiX, ChenSL, et al., 2015. Effect of the Schneiderian membrane on the formation of bone after lifting the floor of the maxillary sinus: an experimental study in dogs. Br J Oral Maxillofac Surg, 53(7):607-612.

[37]SahaS, YangXB, WijayathungaN, et al., 2019. A biomimetic self-assembling peptide promotes bone regeneration in vivo: a rat cranial defect study. Bone, 127:602-611.

[38]SakumaS, FerriM, ImaiH, et al., 2020. Involvement of the maxillary sinus ostium (MSO) in the edematous processes after sinus floor augmentation: a cone-beam computed tomographic study. Int J Implant Dent, 6:35.

[39]ScalaA, BotticelliD, RangelIG, et al., 2010. Early healing after elevation of the maxillary sinus floor applying a lateral access: a histological study in monkeys. Clin Oral Implants Res, 21(12):1320-1326.

[40]ScalaA, BotticelliD, FaedaRS, et al., 2012. Lack of influence of the Schneiderian membrane in forming new bone apical to implants simultaneously installed with sinus floor elevation: an experimental study in monkeys. Clin Oral Implants Res, 23(2):175-181.

[41]SroujiS, KizhnerT, Ben DavidD, et al., 2009. The Schneiderian membrane contains osteoprogenitor cells: in vivo and in vitro study. Calcif Tissue Int, 84(2):138-145.

[42]SroujiS, Ben-DavidD, LotanR, et al., 2010. The innate osteogenic potential of the maxillary sinus (Schneiderian) membrane: an ectopic tissue transplant model simulating sinus lifting. Int J Oral Maxillofac Surg, 39(8):793-801.

[43]SuchaneckaM, GrzelakJ, FarzanehM, et al., 2025. Adipose derived stem cells ‒ sources, differentiation capacity and a new target for reconstructive and regenerative medicine. Biomed Pharmacother, 186:118036.

[44]SuiBD, HuCH, LiuAQ, et al., 2019. Stem cell-based bone regeneration in diseased microenvironments: challenges and solutions. Biomaterials, 196:18-30.

[45]SummersRB, 1994. A new concept in maxillary implant surgery: the osteotome technique. Compendium, 15(2):152, 154-156, 158.

[46]TatumH, 1986. Maxillary and sinus implant reconstructions. Dent Clin North Am, 30(2):207-229.

[47]ToozeRS, MillerKA, SwagemakersSMA, et al., 2023. Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance. Genet Med, 25(9):100883.

[48]WangJ, SunY, LiuYP, et al., 2022. Effects of platelet-rich fibrin on osteogenic differentiation of Schneiderian membrane derived mesenchymal stem cells and bone formation in maxillary sinus. Cell Commun Signal, 20:88.

[49]WengYT, WangHC, WuD, et al., 2022. A novel lineage of osteoprogenitor cells with dual epithelial and mesenchymal properties govern maxillofacial bone homeostasis and regeneration after MSFL. Cell Res, 32(9):814-830.

[50]XieC, LiangRJ, YeJC, et al., 2022. High-efficient engineering of osteo-callus organoids for rapid bone regeneration within one month. Biomaterials, 288:121741.

[51]YangCY, LiZS, LiuY, et al., 2022. Single-cell spatiotemporal analysis reveals cell fates and functions of transplanted mesenchymal stromal cells during bone repair. Stem Cell Rep, 17(10):2318-2333.

[52]YinL, ZhouZX, ShenM, et al., 2019. The human amniotic mesenchymal stem cells (hAMSCs) improve the implant osseointegration and bone regeneration in maxillary sinus floor elevation in rabbits. Stem Cells Int, 2019:9845497.

[53]YuMF, MaL, YuanY, et al., 2021. Cranial suture regeneration mitigates skull and neurocognitive defects in craniosynostosis. Cell, 184 (1):243-256.e18.

[54]YuanY, LohYHE, HanX, et al., 2020. Spatiotemporal cellular movement and fate decisions during first pharyngeal arch morphogenesis. Sci Adv, 6(51):eabb0119.

[55]ZhaoH, FengJF, HoTV, et al., 2015. The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat Cell Biol, 17(4):386-396.

[56]ZhuJX, XiongJB, JiW, 2023. A systematic review of bone marrow stromal cells and periosteum-derived cells for bone regeneration. Tissue Eng Part B Rev, 29(2):103-122.

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Full Text:   <3190>

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Suppl. Mater.: 

CLC number: 

On-line Access: 2026-06-23

Received: 2024-12-02

Revision Accepted: 2025-03-19

Crosschecked: 2026-06-23

Cited: 0

Clicked: 3224

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Misi SI

https://orcid.org/0000-0001-5352-2046

Mengfei YU

https://orcid.org/0000-0002-7700-4697

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