Regenerative Repair of Volumetric Muscle Loss Injury is Sensitive to Age
Regenerative Repair of Volumetric Muscle Loss Injury is Sensitive to Age
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DOI：
10.1089/ten.tea.2019.0034
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发表时间：
2019-08-09
影响因子：
4.1
通讯作者：
Wolchok, Jeffrey C.
中科院分区：
文献类型：
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作者：
Kim, John T.;Kasukonis, Benjamin;Wolchok, Jeffrey C.
在这项研究中，探讨了年龄对治疗体积肌丢失（VML）损伤的再生修复效果的影响。使用辅以自体碎肌肉 (MM) 糊剂的同种异体脱细胞骨骼肌 (DSM) 支架修复 3 个月和 18 个月大动物模型（Fischer 344 大鼠）的胫骨前肌 (TA) VML 损伤。在 3 个月的动物组中，DSM+MM 修复后 TA 峰值收缩力显着改善（正常值的 79%）。然而，在 18 个月大的动物组中，修复后的肌肉力量（正常值的 57%）与未修复的 VML 对照组（正常值的 59%）没有显着差异。在 3 个月的动物组中，DSM+MM 修复通常减少了 VML 修复部位的疤痕，而在 18 个月的组中，修复部位的疤痕和收缩组织的损失很明显。在3个月大的动物中，生肌基因（MyoD、MyoG）、细胞外基质基因（Col I、Col III、TGF-β）和关键伤口愈合基因（TNF-α和IL-1β）的表达增加。或者，在 18 个月大的动物组中检查的所有基因的表达都没有变化。研究结果表明，随着年龄的增长，再生能力下降和纤维化增加可能会给针对 VML 损伤的再生医学策略带来障碍。影响声明 本研究比较了年轻（3 个月）和年老（18 个月）大鼠群体中使用碎肌肉糊和脱细胞肌肉细胞外基质载体的组合修复体积肌肉损失 (VML) 损伤后的恢复情况。目前，VML 修复研究正在针对年轻患者群体进行，但我们的团队是第一个研究年龄对 VML 修复功效影响的团队。我们的研究结果强调了在制定针对老年患者群体的修复策略时考虑 VML 引起的与年龄相关的变化的重要性。
In this study, the influence of age on effectiveness of regenerative repair for the treatment of volumetric muscle loss (VML) injury was explored. Tibialis anterior (TA) VML injuries were repaired in both 3- and 18-month-old animal models (Fischer 344 rat) using allogeneic decellularized skeletal muscle (DSM) scaffolds supplemented with autologous minced muscle (MM) paste. Within the 3-month animal group, TA peak contractile force was significantly improved (79% of normal) in response to DSM+MM repair. However, within the 18-month animal group, muscle force following repair (57% of normal) was not significantly different from unrepaired VML controls (59% of normal). Within the 3-month animal group, repair with DSM+MM generally reduced scarring at the site of VML repair, whereas scarring and a loss of contractile tissue was notable at the site of repair within the 18-month group. Within 3-month animals, expression of myogenic genes (MyoD, MyoG), extracellular matrix genes (Col I, Col III, TGF-beta), and key wound healing genes (TNF-alpha and IL-1 beta) were increased. Alternatively, expression was unchanged across all genes examined within the 18-month animal group. The findings suggest that a decline in regenerative capacity and increased fibrosis with age may present an obstacle to regenerative medicine strategies targeting VML injury. Impact Statement This study compared the recovery following volumetric muscle loss (VML) injury repair using a combination of minced muscle paste and decellularized muscle extracellular matrix carrier in both a younger (3 months) and older (18 months) rat population. Currently, VML repair research is being conducted with the young patient population in mind, but our group is the first to look at the effects of age on the efficacy of VML repair. Our findings highlight the importance of considering age-related changes in response to VML when developing repair strategies targeting an elderly patient population.