優化細胞外囊泡生成和治療潛力的多方面策略

Abstract

細胞外囊泡 (EV) 的治療潛力已引起廣泛關注，應用於包括傷口癒合和再生醫學在內的一系列臨床領域。然而，在優化 EV 的產量和治療品質方面仍面臨挑戰。在此背景下，出現了兩種截然不同但又互相補充的策略。第一種策略是透過使用獨特的細胞形態來增強 EV 的產生，例如人類脂肪幹細胞 (hASC) 的細胞球體培養。這些 3D 培養物已被證明能夠顯著增加 EV 的分泌，同時改善所產生 EV 的血管生成特性，這對於傷口癒合至關重要。在糖尿病大鼠模型中的體內研究表明，EV 治療後膠原蛋白生成、上皮再生和血管生成增強，凸顯了該方法的治療前景。第二種策略著重於將生物電子界面 (BEI) 與奈米結構基底結合，以調節細胞行為並增加 EV 的產生。此方法採用基於暈苯的奈米纖維陣列，並以膠原蛋白等生物相容性層進行改質，從而增強細胞黏附和增殖。在這些細胞奈米結構系統中施加持續電刺激，可使永生化骨髓基質細胞 (IBMSC) 的胞外囊泡 (EV) 釋放量顯著增加 300%，且對 EV 大小和細胞活力無不良影響。這些發現凸顯了 BEI 和奈米結構材料在增強 EV 生成的同時保持細胞完整性的潛力。細胞形態和生物電子介面這兩種策略都代表著優化 EV 生成和療效的有希望的途徑。兩者結合，可提供一種強大而多層面的方法來提高 EV 的產量和質量，從而增強其在再生醫學、傷口癒合等領域的應用潛力。

The therapeutic potential of extracellular vesicles (EVs) has garnered significant interest for a range of clinical applications, including wound healing and regenerative medicine. However, challenges persist in optimizing both the yield and therapeutic quality of EVs. In this context, two distinct yet complementary strategies have emerged. The first involves enhancing EV production through the use of unique cellular morphologies, such as cell spheroid cultures of human adipose-derived stem cells (hASCs). These 3D cultures have been shown to significantly increase EV secretion while improving the angiogenic properties of the produced EVs, which are critical for wound healing. In vivo studies in diabetic rat models demonstrated enhanced collagen production, re-epithelization, and angiogenesis following EV treatment, underlining the therapeutic promise of this approach. The second strategy focuses on the integration of bioelectronic interfaces (BEIs) with nanostructured substrates to modulate cell behavior and increase EV production. By employing coronene-based nanofiber arrays and modifying them with biocompatible layers like collagen, this approach promotes stronger cell adhesion and proliferation. The addition of continuous electrical stimulation to these cell-nanostructure systems led to a significant 300% increase in EV release from Immortalized Bone Marrow Stromal Cells (IBMSCs), with no adverse effects on EV size or cell viability.These findings highlight the potential of BEIs and nanostructured materials to enhance EV production while maintaining cell integrity. Both strategies—cellular morphologies and bioelectronic interfaces—represent promising avenues for optimizing EV production and therapeutic efficacy. When combined, they offer a powerful, multifaceted approach to improving the yield and quality of EVs, enhancing their potential for applications in regenerative medicine, wound healing, and beyond.