Transplantation of iPSC-derived vascular wall-like tissue for improved embolization and reconstruction of aneurysm sac in endovascular aneurysm repair.

Objective: Endoleaks are major complications of endovascular aneurysm repair (EVAR) for treating abdominal aortic aneurysms. Sac embolization is a crucial therapeutic method, in which cell transplantation offers advantages. To attain improved survivability and adaptability, vascular wall-like tissues derived from human induced pluripotent stem cells (iPSCs) were fabricated, and the feasibility of their transplantation for the treatment of endoleaks following EVAR was investigated. Methods: Human iPSCs were cultured in suspension to generate embryoid bodies, which were subsequently differentiated into smooth muscle cell-lineage-associated cells. Cell aggregates were embedded within Matrigel and cultured to form vascular wall-like tissues (VWTs). VWTs were subsequently transplanted into a rat model of aneurysm with endoleak. Histological analyses, including hematoxylin and eosin staining, Masson's trichrome staining, and immunofluorescence, were performed to evaluate the embolization effects and tissue regeneration in the aneurysm sac. Results: Our study successfully established VWTs and a novel rat aneurysm model with endoleak. The transplantation of VWTs resulted in near-complete histological filling of the aneurysm sac over a period of 4 weeks. During this time, the proportions of both solid filling area and nucleated cells increased, while the proportion of acellular structure correspondingly decreased. Intriguingly, the regenerated tissue was predominantly composed of α-SMA Conclusion: Transplantation of VWTs into the aneurysm sac elicited favorable embolization effects and facilitated tissue regeneration and structural reconstruction of the aneurysm sac, which holds potential for long-term embolization of the aneurysm sac in EVAR.