Ageing attenuates bone healing by mesenchymal stem cells in a microribbon hydrogel with a murine long bone critical-size defect model.
Ageing attenuates bone healing by mesenchymal stem cells in a microribbon hydrogel with a murine long bone critical-size defect model.
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DOI：
10.1186/s12979-022-00272-1
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发表时间：
2022-03-12
期刊：
影响因子：
--
通讯作者：
Goodman SB
中科院分区：
文献类型：
--
作者：
Hirata H;Zhang N;Ueno M;Barati D;Kushioka J;Shen H;Tsubosaka M;Toya M;Lin T;Huang E;Yao Z;Wu JY;Zwingenberger S;Yang F;Goodman SB
尽管骨折和假关节在老年人群中的发病率很高，但使用间充质干细胞（MSC）治疗老年患者骨缺损的潜在作用尚未阐明。炎症和先天免疫系统，包括巨噬细胞，在MSC的分化和活化中起着至关重要的作用。我们已经开发了慢病毒转导的白细胞介素4（IL 4）过表达的骨髓间充质干细胞（IL 4-MSC），以使巨噬细胞转化为M2表型，以促进在建立的年轻小鼠临界尺寸骨缺损模型中的骨愈合。在本研究中，我们探索了IL 4-MSC在老年小鼠中的潜力。在15至17个月大的雄性和雌性BALB/c小鼠体内创建2 mm股骨骨干骨缺损，并用外固定装置固定。将具有或不具有MSC包封的微载体（μRB）支架（Sc）植入缺损部位。因此，将小鼠分为三个处理组：仅Sc、Sc + MSC和Sc + IL 4-MSC。手术后6周对小鼠实施安乐死;随后进行MicroCT（µCT）、组织化学和免疫组织化学分析。µCT分析显示，IL 4-MSC组的骨形成显著增强。与单纯Sc组相比，Sc + MSC组和Sc + IL 4-MSC组的新生骨量增加。然而，在所有组中均未观察到骨桥接。H&E染色显示所有组中缺损内的纤维组织。Sc + IL 4-MSC组碱性磷酸酶（ALP）染色增强。Sc + IL 4-MSC组M1巨噬细胞数量减少，M2巨噬细胞数量增加，M2/M1比值显著增加。IL 4促进巨噬细胞极化为M2表型，促进骨生成和血管生成。在µRB支架中添加IL 4-MSC使巨噬细胞极化为M2表型并增加骨形成;然而，在任何标本中均未观察到完全骨桥接。这些结果表明，与年轻动物相反，IL 4-MSC不足以治愈老年小鼠中的临界尺寸骨缺损。在这种具有挑战性的临床情况下，需要额外的治疗策略。
Despite the high incidence of fractures and pseudoarthrosis in the aged population, a potential role for the use of mesenchymal stem cells (MSCs) in the treatment of bone defects in elderly patients has not been elucidated. Inflammation and the innate immune system, including macrophages, play crucial roles in the differentiation and activation of MSCs. We have developed lentivirus-transduced interleukin 4 (IL4) over-expressing MSCs (IL4-MSCs) to polarize macrophages to an M2 phenotype to promote bone healing in an established young murine critical size bone defect model. In the current study, we explore the potential of IL4-MSCs in aged mice. A 2 mm femoral diaphyseal bone defect was created and fixed with an external fixation device in 15- to 17-month-old male and female BALB/c mice. Microribbon (µRB) scaffolds (Sc) with or without encapsulation of MSCs were implanted in the defect sites. Accordingly, the mice were divided into three treatment groups: Sc-only, Sc + MSCs, and Sc + IL4-MSCs. Mice were euthanized six weeks after the surgery; subsequently, MicroCT (µCT), histochemical and immunohistochemical analyses were performed. µCT analysis revealed that bone formation was markedly enhanced in the IL4-MSC group. Compared with the Sc-only, the amount of new bone increased in the Sc + MSCs and Sc + IL4-MSC groups. However, no bridging of bone was observed in all groups. H&E staining showed fibrous tissue within the defect in all groups. Alkaline phosphatase (ALP) staining was increased in the Sc + IL4-MSC group. The Sc + IL4-MSCs group showed a decrease in the number of M1 macrophages and an increase in the number of M2 macrophages, with a significant increase in the M2/M1 ratio. IL4 promotes macrophage polarization to an M2 phenotype, facilitating osteogenesis and vasculogenesis. The addition of IL4-MSCs in the µRB scaffold polarized macrophages to an M2 phenotype and increased bone formation; however, complete bone bridging was not observed in any specimens. These results suggest that IL4-MSCs are insufficient to heal a critical size bone defect in aged mice, as opposed to younger animals. Additional therapeutic strategies are needed in this challenging clinical scenario.
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将人类脂肪来源的间充质干细胞接种到胶原羟基磷灰石支架中，在植入小鼠体内后可促进骨增强。
影响因子：
4.6
作者：
Calabrese G;Giuffrida R;Forte S;Fabbi C;Figallo E;Salvatorelli L;Memeo L;Parenti R;Gulisano M;Gulino R
通讯作者：
Gulino R
影响因子：
20.3
作者：
Ferrucci, L;Corsi, A;Longo, DL
通讯作者：
Longo, DL
影响因子：
4.2
作者：
Hayashi, Ousuke;Katsube, Yoshihiro;Ito, Hiromoto
通讯作者：
Ito, Hiromoto
衰老会影响骨髓巨噬细胞极化：与骨愈合有关。
DOI：
10.1007/s40883-016-0016-5
发表时间：
2016-06
影响因子：
2.6
作者：
Gibon E;Loi F;Córdova LA;Pajarinen J;Lin T;Lu L;Nabeshima A;Yao Z;Goodman SB
通讯作者：
Goodman SB
影响因子：
4
作者：
Chung, Ping-Lin;Zhou, Shuanhu;Eslami, Behnam;Shen, Longxiang;LeBoff, Meryl S.;Glowacki, Julie
通讯作者：
Glowacki, Julie