Development of Extracellular Matrix-Retaining Mesenchymal Stromal Cell Fibers for Novel Endovascular Regenerative Therapy for Aortic Disease

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Abstract

Postoperative aneurysm sac enlargement is a significant clinical issue in endovascular aortic aneurysm repair that is potentially associated with impaired microcirculation in the aneurysmal wall. We developed centimeter-long, fiber-shaped aggregates of human bone marrow-derived mesenchymal stromal cells (HMSC fiber) to function as a scaffold-free cellular construct applicable to endovascular treatment. HMSC fibers were fabricated using a cell self-aggregation technique and optimized by controlling the cell number per unit length to preserve cellular viability and mechanical stability. The resulting fibers retained mesenchymal stromal cell characteristics and endogenous extracellular matrix, facilitating smooth handling and intraluminal delivery without structural collapse. After transcatheter administration into a swine aortic aneurysm model, HMSC fiber-induced fibroconnective tissue formation stimulated neovascularization within the aneurysm cavity. These findings demonstrate the feasibility of HMSC fiber as a controllable and stable platform for localized endovascular cell delivery. Furthermore, this study established their potential utility as a regenerative adjunct to current endovascular treatment for aortic disease.

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