Pharmacologic Mobilization and Chemokine-Directed Recruitment of Mesenchymal Stromal Cells to the Surgically Repaired Rotator Cuff

Document Type

Article

Publication Date

7-1-2025

Publication Title

The American journal of sports medicine

Abstract

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 β(3) 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.

Medical Subject Headings

Animals; Rotator Cuff Injuries; Mesenchymal Stem Cells; Rats; Male; Chemokine CXCL12; Rotator Cuff; Rats, Sprague-Dawley; Cyclams; Heterocyclic Compounds; Chemokine CCL2; Wound Healing; Mesenchymal Stem Cell Transplantation; Disease Models, Animal; Chemokine CCL3; Chemokines; X-Ray Microtomography; Benzylamines

PubMed ID

40444728

ePublication

ePub ahead of print

Volume

53

Issue

8

First Page

1806

Last Page

1816

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