Culture Expansion Alters Human Bone Marrow Derived Mesenchymal Stem Cell Production of Osteoarthritis-relevant Cytokines and Growth Factors.

James E Voos, Andrew Moyal, Ryan Furdock, Arnold I Caplan, Tracey L Bonfield, Jacob G Calcei
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Abstract

Purpose: The purposes of this study were to characterize the human bone marrow derived mesenchymal stem cells (BM-MSCs) production of osteoarthritis-relevant cytokines and growth factors as they are purified and multiplied, a process termed culture expansion, and to compare the immunomodulatory potential of BM-MSCs based on source and medium used for culture expansion.

Methods: BM-MSCs were obtained from iliac crest bone marrow aspirates of four healthy donors. These four BM-MSC cell lines underwent four rounds, or "passages," of the institutional culture expansion protocol, using institutional culture media. The secretory molecules known to play a role in OA-related inflammatory immune response, cartilage degradation and patient symptoms, together called the BM-MSC "secretome," were measured at each passage. Three lines of commercially available BM-MSCs from healthy donors underwent culture expansion by the same protocol, using commercial culture media. The commercial BM-MSCs secretome and the institutional BM-MSCs secretome were compared at each passage. Significance was set at p<0.05.

Results: Institutional BM-MSCs produced less IL-6 at passages 3 (237±113 pg/mL) and 4 (237±113 pg/mL) compared to passages 1 (884±97 pg/mL) and 2 (1071±129 pg/mL; p<0.01). Institutional BM-MSCs produced more MIP-3α at passage 4 than at passage 1 (106±41 vs 32±7 pg/mL; p<0.01). Across passages of culture expansion, institutional BM-MSCs grown on institutional medium expressed more IL-6 (P<0.001), IL-10 (P<0.001), IL-1β (P<0.001), TNFα (P=0.004), and VEGF-C (P=0.003) than commercially available BM-MSCs grown on commercial medium.

Conclusion: Culture expansion alters key molecules within the BM-MSC secretome. Additionally, differences in BM-MSC source and culture medium alter the BM-MSC secretome and its immunomodulatory potential.

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培养扩增可改变人骨髓间充质干细胞产生骨关节炎相关细胞因子和生长因子的情况。
目的:本研究的目的是描述人骨髓间充质干细胞(BM-MSCs)在纯化和增殖过程中产生骨关节炎相关细胞因子和生长因子的特性,这一过程被称为培养扩增,并根据来源和培养扩增所用的培养基比较 BM-MSCs 的免疫调节潜力:方法:从四名健康捐献者的髂嵴骨髓抽吸物中获得 BM-间充质干细胞。这四种 BM-MSC 细胞系经过了四轮或 "传代 "的机构培养扩增方案,并使用了机构培养基。每次传代时,都会对已知在与 OA 相关的炎症免疫反应、软骨降解和患者症状中发挥作用的分泌分子(合称 BM-间充质干细胞 "分泌组")进行测定。来自健康捐献者的三系市售 BM-MSCs 按照相同的方案,使用商业培养基进行了培养扩增。在每个培养阶段,将商用骨髓造血干细胞的分泌组与机构骨髓造血干细胞的分泌组进行比较。显著性以 pResults 为标准:与第 1 期(884±97 pg/mL)和第 2 期(1071±129 pg/mL;p)相比,机构 BM-MSCs 在第 3 期(237±113 pg/mL)和第 4 期(237±113 pg/mL)产生的 IL-6 较少:培养扩增改变了间充质干细胞分泌组中的关键分子。此外,BM-间充质干细胞来源和培养基的不同也会改变BM-间充质干细胞分泌组及其免疫调节潜力。
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来源期刊
CiteScore
9.30
自引率
17.00%
发文量
555
审稿时长
58 days
期刊介绍: Nowhere is minimally invasive surgery explained better than in Arthroscopy, the leading peer-reviewed journal in the field. Every issue enables you to put into perspective the usefulness of the various emerging arthroscopic techniques. The advantages and disadvantages of these methods -- along with their applications in various situations -- are discussed in relation to their efficiency, efficacy and cost benefit. As a special incentive, paid subscribers also receive access to the journal expanded website.
期刊最新文献
Author Reply to Editorial Comment "Autologous Minced Repair of Knee Cartilage Is Safely and Effectively Performed Using Arthroscopic Techniques". Culture Expansion Alters Human Bone Marrow Derived Mesenchymal Stem Cell Production of Osteoarthritis-relevant Cytokines and Growth Factors. Steeper Slope of the Medial Tibial Plateau, Greater Varus Alignment, and Narrower Intercondylar Distance and Notch Width Increase Risk for Medial Meniscus Posterior Root Tears: A Systematic Review. Synthetic Medial Meniscus Implant Demonstrates High Reoperation Rates: Patients Who Retain Implant or Require Implant Exchange SHow Improvement For Post Meniscectomy Knee Pain Is Associated With Clinical Improvement But High Reoperation Rates At 2-Years Post-Operatively. The Knee Anterolateral Ligament is Present in 82% of North American and 65% of European But Only in 46% of Asian Studies: A Systematic Review of Frequency and Anatomy.
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