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骨向诱导和 BMP-4 预培养赋予了双相磷酸钙陶瓷递送的人脐带血间充质基质细胞成骨潜能。

Chondrogenic and BMP-4 primings confer osteogenesis potential to human cord blood mesenchymal stromal cells delivered with biphasic calcium phosphate ceramics.

机构信息

Inserm, UMR 1238, PHY-OS Laboratory, Bone Sarcomas and Remodelling of Calcified Tissues, Faculty of Medicine, University of Nantes, Nantes, France.

National University of Ireland (NUIG), Galway, Ireland.

出版信息

Sci Rep. 2021 Mar 24;11(1):6751. doi: 10.1038/s41598-021-86147-9.

DOI:10.1038/s41598-021-86147-9
PMID:33762629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7991626/
Abstract

Bone marrow mesenchymal stem/stromal cells (BMSCs) show great promise for bone repair, however they are isolated by an invasive bone marrow harvest and their regenerative potential decreases with age. Conversely, cord blood can be collected non-invasively after birth and contains MSCs (CBMSCs) that can be stored for future use. However, whether CBMSCs can replace BMSCs targeting bone repair is unknown. This study evaluates the in vitro osteogenic potential of unprimed, osteogenically primed, or chondrogenically primed CBMSCs and BMSCs and their in vivo bone forming capacity following ectopic implantation on biphasic calcium phosphate ceramics in nude mice. In vitro, alkaline phosphatase (intracellular, extracellular, and gene expression), and secretion of osteogenic cytokines (osteoprotegerin and osteocalcin) was significantly higher in BMSCs compared with CBMSCs, while CBMSCs demonstrated superior chondrogenic differentiation and secretion of interleukins IL-6 and IL-8. BMSCs yielded significantly more cell engraftment and ectopic bone formation compared to CBMSCs. However, priming of CBMSCs with either chondrogenic or BMP-4 supplements led to bone formation by CBMSCs. This study is the first direct quantification of the bone forming abilities of BMSCs and CBMSCs in vivo and, while revealing the innate superiority of BMSCs for bone repair, it provides avenues to induce osteogenesis by CBMSCs.

摘要

骨髓间充质干细胞(BMSCs)在骨修复方面具有巨大的应用潜力,但其分离需要进行有创的骨髓采集,且其再生能力会随年龄的增长而下降。相比之下,脐带血可以在出生后非侵入性地采集,并且其中含有可以储存以备将来使用的间充质干细胞(CBMSCs)。然而,CBMSCs 是否可以替代针对骨修复的 BMSCs 尚不清楚。本研究评估了未经诱导、成骨诱导或软骨诱导的 CBMSCs 和 BMSCs 的体外成骨潜能,以及它们在裸鼠中异位植入双相磷酸钙陶瓷后的体内成骨能力。体外实验结果显示,碱性磷酸酶(细胞内、细胞外和基因表达)和成骨细胞因子(骨保护素和骨钙素)的分泌在 BMSCs 中显著高于 CBMSCs,而 CBMSCs 则表现出更好的软骨分化和白细胞介素 IL-6 和 IL-8 的分泌。BMSCs 的细胞植入和异位骨形成明显多于 CBMSCs。然而,用软骨诱导剂或 BMP-4 对 CBMSCs 进行预诱导可导致 CBMSCs 形成骨。本研究首次直接定量评估了 BMSCs 和 CBMSCs 在体内的成骨能力,虽然揭示了 BMSCs 在骨修复方面的固有优势,但也为诱导 CBMSCs 成骨提供了途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/2975d8d70d11/41598_2021_86147_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/468fbc22ab47/41598_2021_86147_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/09907a5b6ee0/41598_2021_86147_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/2975d8d70d11/41598_2021_86147_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/468fbc22ab47/41598_2021_86147_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/da233b2537b0/41598_2021_86147_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/56a849e6d966/41598_2021_86147_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/d07ada7aba2a/41598_2021_86147_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/e21ed1bb895b/41598_2021_86147_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/09907a5b6ee0/41598_2021_86147_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/440b/7991626/2975d8d70d11/41598_2021_86147_Fig7_HTML.jpg

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