Chronic low back pain is a prevalent disability, often caused by intervertebral disc (IVD) degeneration. Mesenchymal stem cell (MSC) therapy could be a safe and feasible option for repairing the degenerated disc. However, for successful translation to the clinic, various challenges need to be overcome including unwanted adverse effects due to acidic pH, hypoxia, and limited nutrition. Matrilin-3 is an essential extracellular matrix (ECM) component during cartilage development and ossification and exerts chondrocyte protective effects. This study evaluated the effects of matrilin-3-primed adipose-derived MSCs (Ad-MSCs) on the repair of the degenerated disc in vitro and in vivo. We determined the optimal priming concentration and duration and developed an optimal protocol for Ad-MSC spheroid generation. Priming with 10 ng/ml matrilin-3 for 5 days resulted in the highest mRNA expression of type 2 collagen and aggrecan in vitro. Furthermore, Ad-MSC spheroids with a density of 250 cells/microwell showed the increased secretion of favorable growth factors such as transforming growth factor beta (TGF-β1), TGF-β2, interleukin-10 (IL-10), granulocyte colony-stimulating factor (G-CSF), and matrix metalloproteinase 1 (MMP1) and decreased secretion of hypertrophic ECM components. In addition, matrilin-3-primed Ad-MSC spheroid implantation was associated with optimal repair in a rabbit model. Our results suggest that priming MSCs with matrilin-3 and spheroid formation could be an effective strategy to overcome the challenges associated with the use of MSCs for the treatment of IVD degeneration.

中文翻译：

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Matrilin-3引发的脂肪间充质干细胞球体在兔椎间盘退变模型中的功效。

慢性下腰痛是一种普遍的残疾，通常是由椎间盘（IVD）变性引起的。间充质干细胞（MSC）治疗可能是修复变性椎间盘的一种安全可行的选择。然而，为了成功地翻译到临床，需要克服各种挑战，包括由于酸性pH值，缺氧和营养有限而引起的不良副作用。Matrilin-3是软骨发育和骨化过程中必不可少的细胞外基质（ECM）成分，并发挥软骨细胞保护作用。这项研究评估了基质胶3引发的脂肪间充质干细胞（Ad-MSC）在体外和体内对变性椎间盘的修复作用。我们确定了最佳的启动浓度和持续时间，并开发了Ad-MSC球体生成的最佳方案。用10 ng / ml matrilin-3引发5天后，体外2型胶原蛋白和聚集蛋白聚糖的mRNA表达最高。此外，密度为250个细胞/微孔的Ad-MSC球状体显示出有利生长因子的分泌增加，例如转化生长因子β（TGF-β1），TGF-β2，白介素10（IL-10），粒细胞集落-刺激因子（G-CSF）和基质金属蛋白酶1（MMP1）和肥厚性ECM成分的分泌减少。另外，在兔模型中，基质胶3引发的Ad-MSC球体植入与最佳修复相关。我们的结果表明，用基质胶3和球体形成引发MSCs可能是克服与使用MSCs治疗IVD变性相关的挑战的有效策略。