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人毛囊来源的间充质干细胞促进兔跟腱病变模型中的腱修复。

Human hair follicle-derived mesenchymal stem cells promote tendon repair in a rabbit Achilles tendinopathy model.

机构信息

Plastic and Reconstructive Surgery Center, Department of Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.

Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.

出版信息

Chin Med J (Engl). 2023 May 5;136(9):1089-1097. doi: 10.1097/CM9.0000000000002542.

DOI:10.1097/CM9.0000000000002542
PMID:37052142
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10228488/
Abstract

BACKGROUND

Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits.

METHODS

First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo . Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate.

RESULTS

Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P  < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation.

CONCLUSIONS

hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.

摘要

背景

毛囊易于获取,其中包含具有不同发育起源的干细胞,包括间充质干细胞(MSCs),这表明人毛囊(hHF)衍生的 MSCs 具有修复和再生的潜力。然而,hHF-MSCs 在跟腱病(AT)中的作用尚不清楚。本研究探讨了 hHF-MSCs 对兔跟腱修复的影响。

方法

首先,我们提取并鉴定了 hHF-MSCs。然后,构建了兔腱病模型,分析 hHF-MSCs 在体内促进修复的能力。进行解剖观察和病理及生物力学分析,以确定 hHF-MSCs 对 AT 的影响,并通过定量实时聚合酶链反应、酶联免疫吸附试验和免疫组织化学染色,探讨 hHF-MSCs 影响 AT 的分子机制。此外,适当采用独立样本 t 检验、单因素方差分析(ANOVA)和单因素重复测量多元方差分析进行统计分析。

结果

流式细胞术、三系诱导分化试验证实 hHF 来源的干细胞来源于 MSCs。hHF-MSCs 对 AT 的作用表明,跟腱在解剖学上是健康的,跟腱所能承受的最大负荷和羟脯氨酸蛋白质组水平增加。此外,与 AT 组相比,兔 AT 中 hHF-MSCs 处理组的胶原 I 和胶原 III 上调(P<0.05)。对分子机制的分析表明,hHF-MSCs 通过上调 Tenascin-C(TNC)和下调基质金属蛋白酶(MMP)-9 促进胶原纤维再生。

结论

hHF-MSCs 可通过上调胶原 I 和 III 成为促进兔 AT 修复的治疗方法。进一步分析表明,hHF-MSCs 治疗 AT 促进胶原纤维再生,可能是因为 TNC 上调和 MMP-9 下调,这表明 hHF-MSCs 对 AT 更有前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/abe906da1012/cm9-136-1089-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/2c3f6c8c5078/cm9-136-1089-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/305346883883/cm9-136-1089-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/96d0d774b5f7/cm9-136-1089-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/804235ae4f32/cm9-136-1089-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/5b11ae2c4df6/cm9-136-1089-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/c8fb962dbf32/cm9-136-1089-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/abe906da1012/cm9-136-1089-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/2c3f6c8c5078/cm9-136-1089-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/305346883883/cm9-136-1089-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/f62508b601fd/cm9-136-1089-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/e257173b2fdc/cm9-136-1089-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/96d0d774b5f7/cm9-136-1089-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/804235ae4f32/cm9-136-1089-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/5b11ae2c4df6/cm9-136-1089-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/c8fb962dbf32/cm9-136-1089-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdb/10228488/abe906da1012/cm9-136-1089-g009.jpg

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