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犬间充质干细胞的骨再生能力受位点特异性多谱系分化的调节。

The bone regenerative capacity of canine mesenchymal stem cells is regulated by site-specific multilineage differentiation.

作者信息

Bugueño Juan, Li Weihua, Salat Pinky, Qin Ling, Akintoye Sunday O

机构信息

Department of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Department of Orthopedics School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Feb;123(2):163-172. doi: 10.1016/j.oooo.2016.09.011. Epub 2016 Sep 28.

Abstract

OBJECTIVES

Mesenchymal stem cells (MSCs) offer a promising therapy in dentistry because of their multipotent properties. Selecting donor MSCs is crucial because Beagle dogs (canines) commonly used in preclinical studies have shown variable outcomes, and it is unclear whether canine MSCs (cMSCs) are skeletal site specific. This study tested whether jaw and long bone cMSCs have disparate in vitro and in vivo multilineage differentiation capabilities.

STUDY DESIGN

Primary cMSCs were isolated from the mandible (M-cMSCs) and femur (F-cMSCs) of four healthy Beagle dogs. The femur served as the non-oral control. Clonogenic and proliferative abilities were assessed. In vitro osteogenic, chondrogenic, adipogenic, and neural multilineage differentiation were correlated with in vivo bone regeneration and potential for clinical applications.

RESULTS

M-cMSCs displayed two-fold increase in clonogenic and proliferative capacities relative to F-cMSCs (P = .006). M-cMSCs in vitro osteogenesis based on alkaline phosphatase (P = .04), bone sialoprotein (P = .05), and osteocalcin (P = .03), as well as adipogenesis (P = .007) and chondrogenesis (P = .009), were relatively higher and correlated with enhanced M-cMSC bone regenerative capacity. Neural expression markers, nestin and βIII-tubulin, were not significantly different.

CONCLUSIONS

The enhanced differentiation and bone regenerative capacity of mandible MSCs may make them favorable donor graft materials for site-specific jaw bone regeneration.

摘要

目的

间充质干细胞(MSCs)因其多能特性在牙科领域提供了一种有前景的治疗方法。选择供体间充质干细胞至关重要,因为临床前研究中常用的比格犬显示出不同的结果,并且尚不清楚犬间充质干细胞(cMSCs)是否具有骨骼部位特异性。本研究测试了颌骨和长骨的cMSCs在体外和体内的多谱系分化能力是否存在差异。

研究设计

从四只健康比格犬的下颌骨(M-cMSCs)和股骨(F-cMSCs)中分离出原代cMSCs。股骨作为非口腔对照。评估了克隆形成能力和增殖能力。体外成骨、成软骨、成脂和神经多谱系分化与体内骨再生及临床应用潜力相关。

结果

相对于F-cMSCs,M-cMSCs的克隆形成和增殖能力提高了两倍(P = 0.006)。基于碱性磷酸酶(P = 0.04)、骨唾液蛋白(P = 0.05)和骨钙素(P = 0.03)的M-cMSCs体外成骨,以及成脂(P = 0.007)和成软骨(P = 0.009)相对较高,并且与增强的M-cMSC骨再生能力相关。神经表达标志物巢蛋白和βIII-微管蛋白没有显著差异。

结论

下颌骨间充质干细胞增强的分化和骨再生能力可能使其成为用于特定部位颌骨再生的理想供体移植材料。

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