Le Wei, Cheah Andre Eu-Jin, Yao Jeffrey
* Robert A. Chase Hand & Upper Limb Center, Department of Orthopaedic Surgery, Stanford University Medical Center, Redwood City, CA, USA.
† Department of Hand & Reconstructive Microsurgery, National University Hospital, National University Health System, Singapore.
J Hand Surg Asian Pac Vol. 2018 Mar;23(1):47-57. doi: 10.1142/S2424835518500066.
To investigate the effect of myostatin (GDF-8) stimulation of bone marrow derived mesenchymal stem cells (BMSCs) on tenogenesis in the setting of tendon repair. GDF-8 has demonstrated the ability to augment tenogenesis and we sought to identify if this effect could lead to the focused differentiation of pluripotential stem cells down a tenocyte lineage ex vivo.
Cadaveric upper limb flexor tendons were harvested, decellularized and divided into 1 cm segments. Sutures seeded with stem cells were passed through tendon segments to simulate repair. The repaired tendons were then cultured either with or without myostatin for 3, 5, and 7 days. The experiment was also repeated with non-decellularized tendons for a total of 4 groups. The tendons were then evaluated for the expression of scleraxis and tenomodulin, two biomarkers for tendon.
Myostatin stimulation led to an increase in expression of tenomodulin and scleraxis at 5 and 7 days in both the decellularized and non-decellularized tendons. Myostatin increased the differentiation of BMSCs into tenocytes and/or led to the upregulation of tenomodulin and scleraxis production by the native tenocytes present within the non-decellularized tendons.
The addition of myostatin to BMSCs leads to tenocyte differentiation as evidenced by the expression of tenocyte biomarkers, scleraxis and tenomodulin. This effect is maintained in an ex vivo tendon repair model suggestive that these cells survive the passage through tendon tissue and remain metabolically active.
研究肌肉生长抑制素（GDF - 8）刺激骨髓间充质干细胞（BMSCs）对肌腱修复过程中腱生成的影响。GDF - 8已被证明具有增强腱生成的能力，我们试图确定这种作用是否能使多能干细胞在体外定向分化为肌腱细胞谱系。
获取尸体上肢屈肌腱，进行脱细胞处理并切成1厘米长的片段。将接种有干细胞的缝线穿过肌腱片段以模拟修复。然后将修复后的肌腱在有或无肌肉生长抑制素的条件下培养3天、5天和7天。该实验也对未脱细胞的肌腱重复进行，共4组。随后评估肌腱中肌腱蛋白和腱调蛋白这两种肌腱生物标志物的表达情况。
在脱细胞和未脱细胞的肌腱中，肌肉生长抑制素刺激均导致在第5天和第7天时肌腱蛋白和腱调蛋白的表达增加。肌肉生长抑制素增加了BMSCs向肌腱细胞的分化，和/或导致未脱细胞肌腱中原本存在的肌腱细胞上调肌腱蛋白和腱调蛋白的产生。
向BMSCs中添加肌肉生长抑制素会导致肌腱细胞分化，这由肌腱细胞生物标志物肌腱蛋白和腱调蛋白的表达所证实。在体外肌腱修复模型中这种作用得以维持，提示这些细胞在穿过肌腱组织的过程中存活并保持代谢活性。
