Foubert Philippe, Gonzalez Andreina D, Teodosescu Stephan, Berard Felipe, Doyle-Eisele Melanie, Yekkala Krishna, Tenenhaus Mayer, Fraser John K
Cytori Therapeutics, Inc. , San Diego, California.
Lovelace Respiratory Research Institute , Albuquerque, New Mexico.
Adv Wound Care (New Rochelle). 2016 Jul 1;5(7):288-298. doi: 10.1089/wound.2015.0672.
The use of noncultured autologous stromal vascular fraction or clinical grade adipose-derived regenerative cells (ADRCs) is a promising strategy to promote wound healing and tissue repair. Nevertheless, issues regarding the optimal mode of administration remain unclear. The purpose of this study was to compare the effects of local injection and topical spray delivery of ADRCs in a porcine model of thermal burns. Full-thickness thermal burns were created on the dorsum of 10 Gottingen minipigs. Two days following injury, wounds underwent fascial excision and were randomized to receive control vehicle or freshly isolated autologous ADRCs delivered by either multiple injections into or surrounding the wound bed, or by spray onto the wound surface (0.25 × 10 viable cells/cm). Healing was evaluated by planimetry, histopathology, and immunohistochemistry at day 7, 12, 16, 21, and 28 posttreatment. analysis demonstrated that there was no substantial loss of cell number or viability attributable to the spray procedure. Planimetric assessment revealed that delivery of ADRCs by either local injection or topical spray increased wound reepithelialization relative to control at day 14. No significant difference in wound reepithelialization was observed between both delivery approaches. In addition, on day 7 posttreatment, blood vessel density was greater in wounds receiving local or topical spray ADRCs than in the wounds treated with vehicle control. Histopathologic analysis suggests that ADRC treatment may modulate the inflammatory response by reducing neutrophil infiltration at day 7 and 12 posttreatment, irrespective of the route of administration. These data demonstrate that local injection and spray delivery of ADRCs modulate inflammation and improve wound angiogenesis and epithelialization. Importantly, both delivery routes exhibited similar effects on wound healing. Given the greater ease-of-use associated with topical spray delivery, these data support the use of a spray system for autologous ADRC delivery.
使用非培养的自体基质血管成分或临床级脂肪源性再生细胞（ADRCs）是促进伤口愈合和组织修复的一种有前景的策略。然而，关于最佳给药方式的问题仍不明确。本研究的目的是比较ADRCs局部注射和局部喷雾给药在猪热烧伤模型中的效果。在10只哥廷根小型猪的背部造成全层热烧伤。受伤两天后，对伤口进行筋膜切除，并随机分为接受对照载体或新鲜分离的自体ADRCs，通过多次注射到伤口床内或周围，或喷雾到伤口表面（0.25×10个活细胞/cm）。在治疗后第7、12、16、21和28天，通过平面测量、组织病理学和免疫组织化学评估愈合情况。分析表明，喷雾过程不会导致细胞数量或活力的大量损失。平面测量评估显示，在第14天，相对于对照组，通过局部注射或局部喷雾递送ADRCs可增加伤口再上皮化。两种给药方式之间在伤口再上皮化方面未观察到显著差异。此外，在治疗后第7天，接受局部或局部喷雾ADRCs的伤口中的血管密度高于接受载体对照治疗的伤口。组织病理学分析表明，无论给药途径如何，ADRCs治疗可能通过在治疗后第7天和第12天减少中性粒细胞浸润来调节炎症反应。这些数据表明，ADRCs的局部注射和喷雾给药可调节炎症并改善伤口血管生成和上皮化。重要的是，两种给药途径对伤口愈合表现出相似的效果。鉴于局部喷雾给药具有更高的易用性，这些数据支持使用喷雾系统进行自体ADRCs的递送。
