Optimization of a pericyte therapy to improve muscle recovery after limb immobilization.
Optimization of a pericyte therapy to improve muscle recovery after limb immobilization.
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优化周细胞疗法以改善肢体固定后的肌肉恢复。
DOI：
10.1152/japplphysiol.00700.2021
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Boppart,MarniD
中科院分区：
文献类型：
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作者：
Wu,Yu-Fu;Lapp,Samuel;Dvoretskiy,Svyatoslav;Garcia,Gabriela;Kim,Michael;Tannehill,Amanda;Daniels,Laureen;Boppart,MarniD
长期卧床休息或肢体固定可显著降低骨骼肌质量和功能。恢复可能不完全，特别是在老年人中。本实验室最近报道，小鼠制动后血管壁细胞（周细胞）数量受损，在再动员前立即进行适当的更换可以有效地恢复肌纤维的大小。鉴定用于分离最具治疗性的周细胞的单细胞表面标志物将简化优化肌肉恢复的努力。本研究的目的是比较神经/神经胶质抗原2（Cspg 4/NG 2+）和黑色素瘤细胞粘附分子（Mcam/CD 146+）阳性周细胞独特地恢复废用后骨骼肌的能力。将来自成年C57 BL/6 J小鼠的单个后肢通过穿过足中心和腓肠肌体插入的外科缝合钉以完全背屈固定。固定后14天，取出吻合钉，将周细胞（NG 2 + CD 45 − CD 31 −[Lin−]、CD 146 + NG 2 −Lin−或CD 146 +Lin−周细胞）注射到萎缩的胫骨前肌（TA）中。移植和再动员后14天切除TA肌肉。再动员14天后，周细胞移植并没有显著改善肌肉质量或肌纤维横截面积（CSA）。与NG 2+周细胞相比，CD 146+周细胞可显著增加IIa型细胞数量、毛细血管化和胶原重塑（P< 0.05）。我们的研究结果表明，基于CD 146而不是NG 2选择周细胞导致分离出具有高能力的治疗性壁细胞，这些细胞在一段时间的固定后积极重塑骨骼肌。基于神经/神经胶质抗原2（NG 2）或黑素瘤细胞粘附分子的细胞表面标记表达，从小鼠骨骼肌分离周细胞（Mcam/CD 146），然后比较受体小鼠在固定一段时间后恢复骨骼肌的能力。我们报告说，CD 146 +Lin−周细胞比NG 2 +Lin−周细胞具有更高的恢复IIa型纤维数量、毛细血管含量和废用后胶原周转的能力。
Extended bed rest or limb immobilization can significantly reduce skeletal muscle mass and function. Recovery may be incomplete, particularly in older adults. Our laboratory recently reported that vascular mural cell (pericyte) quantity is compromised after immobilization and appropriate replacement immediately before remobilization can effectively recover myofiber size in mice. Identification of a single cell surface marker for isolation of the most therapeutic pericyte would streamline efforts to optimize muscle recovery. The purpose of this study was to compare the capacity for neural/glial antigen 2 (Cspg4/NG2+) and melanoma cell adhesion molecule (Mcam/CD146+) positive pericytes to uniquely recover skeletal muscle post-disuse. A single hindlimb from adult C57BL/6J mice was immobilized in full dorsiflexion via a surgical staple inserted through the center of the foot and body of the gastrocnemius. Fourteen days after immobilization, the staple was removed and pericytes, either NG2+CD45−CD31−[Lin−], CD146+NG2−Lin−, or CD146+Lin−pericytes, were injected into the atrophied tibialis anterior (TA) muscle. TA muscles were excised 14 days after transplantation and remobilization. Pericyte transplantation did not significantly improve muscle mass or myofiber cross-sectional area (CSA) after 14 days of remobilization. However, injection of CD146+pericytes significantly increased Type IIa quantity, capillarization, and collagen remodeling compared with NG2+pericytes (P< 0.05). Our results suggest that selection of pericytes based on CD146 rather than NG2 results in the isolation of therapeutic mural cells with high capacity to positively remodel skeletal muscle after a period of immobilization.NEW & NOTEWORTHYIn this study, pericytes were isolated from mouse skeletal muscle based on cell surface marker expression of neural/glial antigen 2 (NG2) or melanoma cell adhesion molecule (Mcam/CD146) and then compared for the capacity to recover skeletal muscle after a period of immobilization in recipient mice. We report that CD146+Lin−pericytes exhibit higher capacity than NG2+Lin−pericytes to recover Type IIa fiber quantity, capillary content, and collagen turnover after disuse.