The American journal of sports medicine · 2025
Pharmacologic Mobilization and Chemokine-Directed Recruitment of Mesenchymal Stromal Cells to the Surgically Repaired Rotator Cuff.
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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
Аннотация
BACKGROUND: 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.
HYPOTHESIS: MSCs can be pharmacologically mobilized from the peripheral blood and recruited to the operative rotator cuff to enhance tendon-bone healing.
STUDY DESIGN: Controlled laboratory study.
METHODS: 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 β3 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.
RESULTS: 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 (P = .006). Pharmacological MSC mobilization was associated with significantly increased peak stress (P = .039), significantly increased elastic modulus (P = .037), and a nonsignificant increase in both equilibrium stress (P = .057) and ultimate stress (P = .058). Local MCP-1 delivery was associated with significant improvements in tenocyte morphology.
CONCLUSION: 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.
CLINICAL RELEVANCE: 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.
HYPOTHESIS: MSCs can be pharmacologically mobilized from the peripheral blood and recruited to the operative rotator cuff to enhance tendon-bone healing.
STUDY DESIGN: Controlled laboratory study.
METHODS: 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 β3 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.
RESULTS: 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 (P = .006). Pharmacological MSC mobilization was associated with significantly increased peak stress (P = .039), significantly increased elastic modulus (P = .037), and a nonsignificant increase in both equilibrium stress (P = .057) and ultimate stress (P = .058). Local MCP-1 delivery was associated with significant improvements in tenocyte morphology.
CONCLUSION: 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.
CLINICAL RELEVANCE: 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.