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自体间充质基质细胞和胶原微载体治疗自然退变犬腰椎间盘：一项前瞻性临床研究。

Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study.

机构信息

1 Vetsuisse faculty of the University of Zurich, Zurich, Switzerland.

2 Swiss Paraplegic Research, Nottwil, Switzerland.

出版信息

Cell Transplant. 2019 Feb;28(2):201-211. doi: 10.1177/0963689718815459. Epub 2018 Nov 29.

DOI:10.1177/0963689718815459
PMID:30488736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6362527/
Abstract

Intervertebral disc (IVD) degeneration is a frequent disease in modern societies and at its later stages is likely to cause chronic low back pain. Although many studies have been published, the available treatments for IVD degeneration fail to promote regeneration or even marginal repair of the IVD structure. In this study, we aimed to establish veterinary canine patients as a translational large animal model that recapitulates IVD degeneration that occurs in humans, and to investigate the suitability of intradiscal application of mesenchymal stromal cells (MSC). Twenty client-owned dogs diagnosed with spontaneous degenerative lumbosacral IVD and low back pain were included in the study. Autologous MSC were isolated from bone marrow and cultured for 2 weeks. Prior to injection, MSC were attached on collagen microcarriers for delivery, with or without TGF-β1 crosslinking. After decompressive spinal surgery, dogs received an intradiscal injection of MSC-microcarriers ( n = 11), MSC-TGF-β1-microcarriers ( n = 6) or microcarriers only (control, n = 3). MSC-microcarriers were initially evaluated in vitro and ex vivo, to test cell chondrogenic potential and biomechanical properties of the microcarriers, respectively. Clinical performance and Pfirrmann grading were evaluated at 10 months after the injection by magnetic resonance imaging. MSC differentiated successfully in vitro towards chondrogenic phenotype and biomechanical tests showed no significant differences of IVD stiffness after microcarrier injection. In vivo injection was successful in all dogs, without any visible leakage, and clinical functioning was restored back to normality. However, postoperative Pfirrmann grade remained identical in all dogs, and formation of Schmorl's nodes was detected in 45% of dogs. This side effect was reduced by halving the injection volume, which was then observed only in 11% of dogs. In conclusion, we observed marked clinical improvement in all groups, despite the formation of Schmorl's nodes, but microcarriers and MSC failed to regenerate the structure of degenerated IVD.

摘要

椎间盘（IVD）退变是现代社会的常见疾病，在晚期阶段可能导致慢性下腰痛。尽管已经发表了许多研究，但现有的 IVD 退变治疗方法不能促进 IVD 结构的再生甚至是边缘修复。在这项研究中，我们旨在建立兽医犬患者作为一种翻译大动物模型，重现人类发生的 IVD 退变，并研究椎间盘内应用间充质基质细胞（MSC）的适宜性。 20 只被诊断为自发性退行性腰骶 IVD 和下腰痛的患犬被纳入研究。从骨髓中分离出自体 MSC 并培养 2 周。在注射前，MSC 被附着在胶原蛋白微载体上用于递送，有或没有 TGF-β1 交联。减压脊柱手术后，犬接受 MSC-微载体（n = 11）、MSC-TGF-β1-微载体（n = 6）或微载体（对照，n = 3）的椎间盘内注射。MSC-微载体首先在体外和体外进行评估，分别测试细胞软骨形成潜力和微载体的生物力学特性。注射后 10 个月通过磁共振成像评估临床性能和 Pfirrmann 分级。MSC 在体外成功分化为软骨形成表型，生物力学测试显示微载体注射后 IVD 刚度无明显差异。所有犬的体内注射均成功，无可见渗漏，临床功能恢复正常。然而，所有犬的 Pfirrmann 分级术后保持相同，45%的犬检测到 Schmorl 节点形成。将注射体积减半可减少这种副作用，仅在 11%的犬中观察到。总之，尽管形成了 Schmorl 节点，但我们观察到所有组的临床症状均明显改善，但微载体和 MSC 未能再生退变的 IVD 结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/13407a87cdab/10.1177_0963689718815459-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/0ea8b575fe75/10.1177_0963689718815459-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/aa2b6c5db408/10.1177_0963689718815459-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/efddd40fac61/10.1177_0963689718815459-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/13407a87cdab/10.1177_0963689718815459-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/0ea8b575fe75/10.1177_0963689718815459-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/aa2b6c5db408/10.1177_0963689718815459-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/efddd40fac61/10.1177_0963689718815459-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a5/6362527/13407a87cdab/10.1177_0963689718815459-fig4.jpg

相似文献

[1]
Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study.

Cell Transplant. 2018-11-29

[2]
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[3]
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Vet Res Commun. 2025-8-28

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JOR Spine. 2025-8-13

[3]
Tissue engineering strategies for treating intervertebral disc degeneration.

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[4]
Current Advances in Mesenchymal Stem Cell Therapies Applied to Wounds and Skin, Eye, and Neuromuscular Diseases in Companion Animals.

Animals (Basel). 2024-4-30

[5]
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Bioengineering (Basel). 2023-6-12

[6]
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[7]
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[8]
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[9]
Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy.

Front Cell Dev Biol. 2021-3-19

[10]
Cell-based strategies for IVD repair: clinical progress and translational obstacles.

Nat Rev Rheumatol. 2021-3

本文引用的文献

[1]
Bone Marrow-Derived Mesenchymal Stem Cells as Autologous Therapy in Dogs with Naturally Occurring Intervertebral Disc Disease: Feasibility, Safety, and Preliminary Results.

Tissue Eng Part C Methods. 2017-6-22

[2]
Multipotent Mesenchymal Stem Cell Treatment for Discogenic Low Back Pain and Disc Degeneration.

Stem Cells Int. 2016

[3]
Growth Factors Cross-Linked to Collagen Microcarriers Promote Expansion and Chondrogenic Differentiation of Human Mesenchymal Stem Cells.

Tissue Eng Part A. 2015-10

[4]
Injectable microcarriers as human mesenchymal stem cell support and their application for cartilage and degenerated intervertebral disc repair.

Eur Cell Mater. 2015-1-12

[5]
Canine Mesenchymal Stem Cell Potential and the Importance of Dog Breed: Implication for Cell-Based Therapies.

Cell Transplant. 2015

[6]
Delivering mesenchymal stem cells in collagen microsphere carriers to rabbit degenerative disc: reduced risk of osteophyte formation.

Tissue Eng Part A. 2014-5

[7]
Schmorl's nodes: current pathophysiological, diagnostic, and therapeutic paradigms.

Neurosurg Rev. 2013-8-18

[8]
Comparing the osteogenic potential of canine mesenchymal stem cells derived from adipose tissues, bone marrow, umbilical cord blood, and Wharton's jelly for treating bone defects.

J Vet Sci. 2012-9

[9]
Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs.

J Vet Med Sci. 2012-12

[10]
Isolation, characterization, and in vitro proliferation of canine mesenchymal stem cells derived from bone marrow, adipose tissue, muscle, and periosteum.

Am J Vet Res. 2012-8

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