Beckman Laser Institute Korea, Dankook University, Cheonan 31116, Republic of Korea.
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea.
Cells. 2023 Apr 13;12(8):1146. doi: 10.3390/cells12081146.
Diabetes mellitus contributes to 15-25% of all chronic foot ulcers. Peripheral vascular disease is a cause of ischemic ulcers and exacerbates diabetic foot disease. Cell-based therapies are viable options to restore damaged vessels and induce the formation of new vessels. Adipose-derived stem cells (ADSCs) have the potential for angiogenesis and regeneration because of their greater paracrine effect. Preclinical studies are currently using other forced enhancement techniques (e.g., genetic modification or biomaterials) to increase the efficacy of human ADSC (hADSC) autotransplantation. Unlike genetic modifications and biomaterials, many growth factors have been approved by the equivalent regulatory authorities. This study confirmed the effect of enhanced human ADSC (ehADSC)s with a cocktail of FGF and other pharmacological agents to promote wound healing in diabetic foot disease. In vitro, ehADSCs exhibited a long and slender spindle-shaped morphology and showed significantly increased proliferation. In addition, it was shown that ehADSCs have more functionalities in oxidative stress toleration, stem cell stemness, and mobility. In vivo, the local transplantation of 1.2 × 10 hADSCs or ehADSCs was performed in animals with diabetes induced by STZ. The ehADSC group showed a statistically decreased wound size and increased blood flow compared with the hADSC group and the sham group. Human Nucleus Antigen (HNA) positive cells were observed in some ADSC-transplanted animals. The ehADSC group showed a relatively higher portion of HNA-positive animals than the hADSC group. The blood glucose levels showed no significant difference among the groups. In conclusion, the ehADSCs showed a better performance in vitro, compared with conventional hADSCs. Additionally, a topical injection of ehADSCs into diabetic wounds enhanced wound healing and blood flow, while improving histological markers suggesting revascularization.
糖尿病导致 15-25%的慢性足部溃疡。周围血管疾病是缺血性溃疡的原因，并使糖尿病足病恶化。基于细胞的疗法是恢复受损血管并诱导新血管形成的可行选择。脂肪来源的干细胞 (ADSCs) 由于其更大的旁分泌作用，具有血管生成和再生的潜力。目前，临床前研究正在使用其他强制增强技术（例如基因修饰或生物材料）来提高人 ADSC（hADSC）自体移植的疗效。与基因修饰和生物材料不同，许多生长因子已被等效监管机构批准。这项研究证实了 FGF 和其他药理学制剂鸡尾酒增强的人 ADSC（ehADSC）对糖尿病足病伤口愈合的作用。在体外，ehADSCs 表现出长而细长的纺锤形形态，并显示出明显增加的增殖。此外，还表明 ehADSCs 在氧化应激耐受、干细胞干性和迁移能力方面具有更多功能。在体内，通过 STZ 诱导糖尿病动物进行局部移植 1.2×10 hADSCs 或 ehADSCs。与 hADSC 组和假手术组相比，ehADSC 组的伤口面积明显减小，血流量增加。在一些 ADSC 移植动物中观察到人类核抗原 (HNA) 阳性细胞。与 hADSC 组相比，ehADSC 组 HNA 阳性动物的比例相对较高。各组的血糖水平无显著差异。总之，与常规 hADSCs 相比，ehADSCs 在体外表现出更好的性能。此外，将 ehADSCs 局部注射到糖尿病伤口中可增强伤口愈合和血流，同时改善提示再血管化的组织学标志物。
