Side population hematopoietic stem cells promote wound healing in diabetic mice

Side population hematopoietic stem cells promote wound healing in diabetic mice
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DOI:
10.1097/01.prs.0000267696.98789.66
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发表时间:
2007-08-01
影响因子:
3.6
通讯作者:
Orgill, Dennis P.
Orgill, Dennis P.
中科院分区:
医学1区
文献类型:
--
作者:
Chan, Rodney K.;Garfein, Evan;Orgill, Dennis P.

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背景:早期证据表明干细胞在正常伤口愈合中发挥作用。各种受损的伤口愈合状态可能是由于干细胞谱系的缺陷造成的。作者试图证明一种新的淋巴祖细胞亚群将促进糖尿病小鼠伤口的愈合。方法:从C57B16/J股骨获取骨髓细胞,根据其排出活性染料Hoechst 33342的能力以及CD7和CD34标记的存在与否将其分为侧群和主群。Lepr db/db和野生型小鼠背部1 cm(2)全切伤创面伤后次日,分别用侧群或主群细胞和对照溶液1次局部涂抹,每组12只。伤口闭合后进行计算机平面测量。结果:局部局部群体治疗对糖尿病动物创面愈合有显著影响,术后第7天创面闭合率(35+/-7.2%)高于主要群体细胞治疗组(16+/-4.9%)或生理盐水对照组(14+/-6.7%)(p<0.05)。当给已经拥有正常干细胞库的野生型小鼠注射侧群细胞时,伤口有更好的愈合趋势,但没有发现显著差异。结论:侧群处理的糖尿病小鼠创面比主群或对照处理的创面愈合得更快,这表明一个干细胞亚群,而不是大多数干细胞亚群,具有改善愈合过程的潜力。需要进一步的研究来研究愈合的机制,并探索其作为治疗剂的潜力。
Background: Early evidence suggests that stem cells play a role in normal wound healing. Various impaired wound-healing states might be due to a deficiency in the stem cell repertoire. The authors sought to demonstrate that a new subset of lymphoid progenitor murine hematopoietic stem cells will accelerate wound healing in diabetic mice.Methods: Bone marrow cells were harvested from C57B16/J femurs and separated into side and main populations based on their ability to efflux the vital dye Hoechst 33342 and the presence or absence of CD7 and CD34 markers. Side or main population cells and control solution were applied once topically to 1-cm(2) full-thickness dorsal excisional wounds in lepr db/db and wild-type mice on the day after wounding (n = 12 in each group). Wound closure was followed by computer planimetry. Wounds were harvested after 7 and 25 days for histological analysis.Results: Topical side population treatment had a significant effect on wound closure in diabetic animals, with a higher percentage of wound closure (35 +/- 7.2 percent) in this group on postoperative day 7 compared with animals treated with either main population cells (16 +/- 4.9 percent) or a vehicle control using saline (14 +/- 6.7 percent) (p < 0.05). When side population cells were given to wild-type mice that already had a normal stem cell repertoire, there was a trend toward better wound closure, but no significant differences were found.Conclusions: Side population-treated wounds healed more quickly than main population-or control-treated wounds in diabetic mice, suggesting that one stem cell subpopulation, but not the majority, harbors the potential for improving the healing process. Further studies are needed to investigate the mechanism of healing and to explore its potential as a therapeutic agent.