Pharmacological mobilization of endogenous stem cells significantly promotes skin regeneration after full-thickness excision: the synergistic activity of AMD3100 and tacrolimus.

Pharmacological mobilization of endogenous stem cells significantly promotes skin regeneration after full-thickness excision: the synergistic activity of AMD3100 and tacrolimus.
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DOI:
10.1038/jid.2014.162
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发表时间:
2014-09
影响因子:
6.5
通讯作者:
Sun, Zhaoli
Sun, Zhaoli
中科院分区:
医学1区
文献类型:
--
作者:
Lin, Qing;Wesson, Russell N.;Maeda, Hiromichi;Wang, Yongchun;Cui, Zhu;Liu, Jun O.;Cameron, Andrew M.;Gao, Bin;Montgomery, Robert A.;Williams, George M.;Sun, Zhaoli

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干细胞疗法已在治疗包括皮肤伤口在内的多种病理方面显示出希望,但实际应用仍然难以捉摸。在这里,我们证明了由AMD 3100和低剂量他克莫司产生的内源性干细胞动员能够将手术切除产生的全层伤口的完全愈合时间缩短25%。同样重要的是,愈合伴随着减少疤痕和毛囊再生。在寻找机制时,我们发现AMD 3100联合低剂量他克莫司动员了更多的谱系阴性c-Kit+、CD 34+和CD 133+干细胞。低剂量他克莫司还增加了伤口部位中携带SDF-1的巨噬细胞的数量,放大了动员的干细胞进入伤口的“拉力”。谱系追踪证实了CD 133干细胞在促进毛细血管和毛囊新生中的关键作用,有助于更快速和完美的愈合。我们的发现为伤口愈合和组织再生提供了一种重要的治疗方法。
Stem cell therapy has shown promise in treating a variety of pathologies including skin wounds, but practical applications remain elusive. Here we demonstrate that endogenous stem cell mobilization produced by AMD3100 and low-dose Tacrolimus is able to reduce by 25% the time of complete healing of full-thickness wounds created by surgical excision. Equally important, healing was accompanied by reduced scar and regeneration of hair follicles. Searching for mechanisms, we found that AMD3100 combined with low-dose Tacrolimus mobilized increased number of lineage-negative c-Kit+, CD34+ and CD133+ stem cells. Low-dose Tacrolimus also increased the number of SDF-1 bearing macrophages in the wounds sites amplifying the “pull” of mobilized stem cells into the wound. Lineage tracing demonstrated the critical role of CD133 stem cells in enhanced capillary and hair follicle neogenesis contributing to more rapid and perfect healing. Our findings offer a significant therapeutic approach to wound healing and tissue regeneration.
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