Baker Kevin C, Fleischer Mackenzie, Newton Michael D, Galasso Lisa, Cavinatto Leonardo, Weisz Kevin M, Hartner Samantha, Maerz Tristan, Lammlin Lindsey, Baker Erin A, Allen Answorth A, Bedi Asheesh
Henry Ford Health + Michigan State University Health Sciences, Detroit, Michigan, USA.
Bone & Joint Center, Department of Orthopaedic Surgery, Henry Ford Health, Detroit, Michigan, USA.
Am J Sports Med. 2025 Jul;53(8):1806-1816. doi: 10.1177/03635465251341439. Epub 2025 May 30.
Mesenchymal stromal cell (MSC) techniques represent a promising method to enhance the surgical repair of rotator cuff tears. To eliminate the resource-intensive process of cell isolation and culture expansion, a method to recruit endogenous MSCs was investigated in an established rat model of rotator cuff repair.
MSCs can be pharmacologically mobilized from the peripheral blood and recruited to the operative rotator cuff to enhance tendon-bone healing.
Controlled laboratory study.
The rat model of supraspinatus tendon detachment and acute surgical repair was used to compare the ability of 3 different chemokines (SDF-1β, MIP-3α, and MCP-1) to recruit optically labeled MSCs to the operative shoulder from circulation. Additional experimentation was undertaken to assess the effects of pharmacological MSC mobilization using a combination of a β adrenoreceptor agonist (BRL37344) and a CXCR4 antagonist (AMD3100) on chemokine-directed recruitment to the shoulder. Finally, the effects of this therapeutic strategy on tendon-bone healing were assessed.
MCP-1-loaded hydrogels recruited the greatest number of MSCs from circulation. MCP-1-driven MSC recruitment was significantly enhanced by a regimen of subcutaneous BRL37344 and AMD3100. Postmortem micro-computed tomography imaging performed at a 6-week endpoint revealed that local MCP-1 delivery was associated with significant reductions in trabecular spacing and apparent mineral density, and a significant increase in trabecular number, while pharmacological MSC mobilization had no significant effects. MCP-1 delivery was associated with a lower tendon cross-sectional area and a significant increase in percent relaxation ( = .006). Pharmacological MSC mobilization was associated with significantly increased peak stress ( = .039), significantly increased elastic modulus ( = .037), and a nonsignificant increase in both equilibrium stress ( = .057) and ultimate stress ( = .058). Local MCP-1 delivery was associated with significant improvements in tenocyte morphology.
Endogenous MSCs can be pharmacologically mobilized into peripheral blood and recruited to the site of rotator cuff repair via local delivery of MCP-1. This therapeutic strategy was associated with improvements in the static and dynamic mechanical properties of the tendon-bone interface.
The healing of rotator cuff repairs represents an ongoing clinical challenge in orthopaedic surgery. This study demonstrates a method to use endogenous MSCs to enhance healing of the rotator cuff.
间充质基质细胞（MSC）技术是一种有望增强肩袖撕裂手术修复效果的方法。为消除细胞分离和培养扩增这一资源密集型过程，在已建立的肩袖修复大鼠模型中研究了一种募集内源性MSC的方法。
MSC可通过药物从外周血中动员出来，并募集到手术修复的肩袖部位，以增强腱骨愈合。
对照实验室研究。
采用冈上肌腱离断和急性手术修复的大鼠模型，比较3种不同趋化因子（SDF-1β、MIP-3α和MCP-1）从循环中募集光学标记的MSC至手术肩部的能力。进行了额外实验，以评估使用β肾上腺素能受体激动剂（BRL37344）和CXCR4拮抗剂（AMD3100）联合用药进行药物性MSC动员对趋化因子引导的向肩部募集的影响。最后，评估了该治疗策略对腱骨愈合的影响。
负载MCP-1的水凝胶从循环中募集的MSC数量最多。皮下注射BRL37344和AMD3100的方案显著增强了MCP-1驱动的MSC募集。在6周终点进行的死后微型计算机断层扫描成像显示，局部递送MCP-1与小梁间距和表观矿物质密度显著降低以及小梁数量显著增加有关，而药物性MSC动员没有显著影响。递送MCP-1与较低的肌腱横截面积和松弛百分比显著增加有关（P = 0.006）。药物性MSC动员与峰值应力显著增加（P = 0.039）、弹性模量显著增加（P = 0.037）以及平衡应力（P = 0.057）和极限应力（P = 0.058）均有非显著性增加有关。局部递送MCP-1与成纤维细胞形态显著改善有关。
内源性MSC可通过药物动员进入外周血，并通过局部递送MCP-1募集到肩袖修复部位。这种治疗策略与腱骨界面的静态和动态力学性能改善有关。
肩袖修复的愈合是骨科手术中一个持续存在的临床挑战。本研究展示了一种利用内源性MSC增强肩袖愈合的方法。
