Veronesi Francesca, Della Bella Elena, Torricelli Paola, Pagani Stefania, Fini Milena
Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy.
Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
Cytotherapy. 2015 Nov;17(11):1536-44. doi: 10.1016/j.jcyt.2015.07.007. Epub 2015 Aug 21.
Aging and estrogen deficiency play a pivotal role in reducing tenocyte proliferation, collagen turnover and extracellular matrix remodeling. Mesenchymal stromal cells are being studied as an alternative for tendon regeneration, but little is known about the molecular events of adipose-derived mesenchymal stromal cells (ADSCs) on tenocytes in tendons compromised by aging and estrogen deficiency. The present in vitro study aims to compare the potential therapeutic effects of ADSCs, harvested from healthy young (sham) and aged estrogen-deficient (OVX) subjects, for tendon healing.
An indirect co-culture system was set up with ADSCs, isolated from OVX or sham rats, and tenocytes from OVX rats. Cell proliferation, healing rate and gene expression were evaluated in both a standard culture condition and a microwound-healing model.
It was observed that tenocyte proliferation, healing rate and collagen expression improved after the addition of sham ADSCs in both culture situations. OVX ADSCs also increased tenocyte proliferation and healing rate but less compared with sham ADSCs. Decorin and Tenascin C expression increased in the presence of OVX ADSCs.
Findings suggest that ADSCs might be a promising treatment for tendon regeneration in advanced age and estrogen deficiency. However, some differences between allogenic and autologous cells were found and should be investigated in further in vivo studies. It appears that allogenic ADSCs improve tenocyte proliferation, collagen expression and the healing rate more than autologous cells. Autologous cells increase collagen expression only in the absence of an injury and increase Decorin and Tenascin C more than allogenic cells.
衰老和雌激素缺乏在降低肌腱细胞增殖、胶原蛋白更新及细胞外基质重塑方面起关键作用。间充质基质细胞正作为肌腱再生的替代方法进行研究,但对于脂肪来源的间充质基质细胞(ADSCs)在因衰老和雌激素缺乏而受损的肌腱中对肌腱细胞的分子作用知之甚少。本体外研究旨在比较从健康年轻(假手术)和老年雌激素缺乏(卵巢切除)受试者获取的ADSCs对肌腱愈合的潜在治疗效果。
建立间接共培养系统,将从卵巢切除或假手术大鼠分离的ADSCs与卵巢切除大鼠的肌腱细胞共培养。在标准培养条件和微创伤愈合模型中评估细胞增殖、愈合率及基因表达。
观察到在两种培养情况下添加假手术ADSCs后,肌腱细胞增殖、愈合率及胶原蛋白表达均得到改善。卵巢切除ADSCs也增加了肌腱细胞增殖和愈合率,但与假手术ADSCs相比增幅较小。在卵巢切除ADSCs存在的情况下,核心蛋白聚糖和腱生蛋白C表达增加。
研究结果表明,ADSCs可能是治疗高龄和雌激素缺乏状态下肌腱再生的一种有前景的方法。然而,发现同种异体细胞和自体细胞之间存在一些差异,应在进一步的体内研究中进行调查。似乎同种异体ADSCs比自体细胞更能提高肌腱细胞增殖、胶原蛋白表达和愈合率。自体细胞仅在无损伤时增加胶原蛋白表达,且比同种异体细胞更多地增加核心蛋白聚糖和腱生蛋白C的表达。