Topical Lineage-Negative Progenitor-Cell Therapy for Diabetic Wounds
Topical Lineage-Negative Progenitor-Cell Therapy for Diabetic Wounds
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DOI：
10.1097/prs.0b013e318188217b
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发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Warren, Stephen M.
中科院分区：
文献类型：
--
作者：
Lin, Clarence D.;Allori, Alexander C.;Warren, Stephen M.
背景：糖尿病伤口愈合受损部分是由于间充质祖细胞追踪缺陷。理论上，这些缺陷可以通过将纯化的祖细胞直接施用到糖尿病伤口来克服。作者假设，这些祖细胞将分化成内皮细胞，增加伤口血管，并改善伤口愈合。方法：谱系阴性祖细胞分离野生型小鼠骨髓磁性细胞分选，悬浮在胶原蛋白基质，局部应用于全层切除背侧皮肤伤口糖尿病小鼠。应用谱系阳性造血细胞或脱细胞胶原基质作为比较对照（每组n = 16;总共n = 48）。通过形态测定法计算闭合时间和闭合百分比。在第7、14、21和28天收获伤口，然后处理、切片、染色（凝集素/DiI和CD 31），并定量血管分布。与谱系阳性细胞相比，用谱系阴性细胞治疗的伤口显示出显著缩短的闭合时间（14天）。与谱系阳性组（p <0.01）和胶原对照组（p <0.01）相比，在第14天的闭合百分比显著改善。标记的谱系阴性细胞在伤口中存活28天，而谱系阳性细胞在7天后不存在。谱系阴性而非谱系阳性的细胞分化为内皮细胞。血管密度和血管横截面积显着较高的谱系阴性wounds.Conclusion：局部祖细胞治疗成功地加速糖尿病伤口愈合，改善伤口血管。（Plast。重建122：1341，2008）。
Background: Impaired diabetic wound healing is due, in part, to defects in mesenchymal progenitor cell tracking. Theoretically, these defects may be overcome by administering purified progenitor cells directly to the diabetic wound. The authors hypothesize that these progenitor cells will differentiate into endothelial cells, increase wound vascularity, and improve wound healing.Methods: Lineage-negative progenitor cells were isolated from wild-type murine bone marrow by magnetic cell sorting, suspended in a collagen matrix, and applied topically to full-thickness excisional dorsal cutaneous wounds in diabetic mice. Application of lineage-positive hematopoietic cells or acellular collagen matrix served as comparative controls (n = 16 for each group; n = 48 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 7, 14, 21, and 28 days and then processed, sectioned, stained (lectin/DiI and CD31), and vascularity was quantified.Results: Wounds treated with lineage-negative cells demonstrated a significantly decreased time to closure (14 days) compared with lineage-positive (21 days, p = 0.013) and collagen controls (28 days, p = 0.004), and a significant improvement in percentage closure at 14 days compared with the lineage-positive group (p < 0.01) and the collagen control (p < 0.01). Fluorescently tagged lineage-negative cells remained viable in the wound for 28 days, whereas lineage-positive cells were not present after 7 days. Lineage-negative, but not lineage-positive, cells differentiated into endothelial cells. Vascular density and vessel cross-sectional area were significantly higher in lineage-negative wounds.Conclusion: Topical progenitor-cell therapy successfully accelerates diabetic wound closure and improves wound vascularity. (Plast. Reconstr. Surg. 122: 1341, 2008.)