Diabetes impairs stem cell and proangiogenic cell mobilization in humans.
Diabetes impairs stem cell and proangiogenic cell mobilization in humans.
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DOI：
10.2337/dc12-1084
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发表时间：
2013-04
期刊：
影响因子：
16.2
通讯作者：
Avogaro A
中科院分区：
文献类型：
--
作者：
Fadini GP;Albiero M;Vigili de Kreutzenberg S;Boscaro E;Cappellari R;Marescotti M;Poncina N;Agostini C;Avogaro A
糖尿病（DM）增加心血管风险，至少部分是由于缺乏来自骨髓（BM）的血管再生细胞。在实验模型中，DM引起形态和功能BM改变，但人类DM中BM功能的信息缺失。在此，我们试图测定患有和不患有DM的受试者中干细胞和促血管生成细胞的动员。在一项前瞻性试验（NCT 01102699）中，我们在24例DM患者（10例1型和14例2型）和14例非DM患者中检测了BM对5 μg/kg人重组粒细胞集落刺激因子（hrG-CSF）的反应性。在hrG-CSF之前和之后24小时，我们定量循环干/祖细胞和总的和分类的白色血细胞计数。我们还评估了在体内的促血管生成能力的外周血单核细胞使用基质胶塞测定。作为对hrG-CSF的响应，在无DM的受试者中，CD 34+细胞和其他祖细胞表型的水平增加。DM患者的CD 34+、CD 133+、CD 34 + CD 133+造血干细胞和CD 133 +KDR+内皮祖细胞的动员显著受损，与潜在的混杂因素无关。在无DM的对照受试者中，给予hrG-CSF后，外周血单核细胞的体内血管生成能力显著增加，但在DM患者中没有增加。DM还与不能上调CD 34+细胞上的CD 26/DPP-4相关，这是粒细胞集落刺激因子的动员作用所必需的。干细胞和促血管生成细胞动员对hrG-CSF的反应在DM中受损，可能是因为不适应的CD 26/DPP-4调节。这些改变可能会阻碍组织修复，并有利于心血管并发症的发展。
Diabetes mellitus (DM) increases cardiovascular risk, at least in part, through shortage of vascular regenerative cells derived from the bone marrow (BM). In experimental models, DM causes morphological and functional BM alterations, but information on BM function in human DM is missing. Herein, we sought to assay mobilization of stem and proangiogenic cells in subjects with and without DM. In a prospective trial (NCT01102699), we tested BM responsiveness to 5 μg/kg human recombinant granulocyte colony–stimulating factor (hrG-CSF) in 24 individuals with DM (10 type 1 and 14 type 2) and 14 individuals without DM. Before and 24 h after hrG-CSF, we quantified circulating stem/progenitor cells and total and differential white blood cell counts. We also evaluated in vivo the proangiogenic capacity of peripheral blood mononuclear cells using the Matrigel plug assay. In response to hrG-CSF, levels of CD34+ cells and other progenitor cell phenotypes increased in subjects without DM. Patients with DM had significantly impaired mobilization of CD34+, CD133+, and CD34+CD133+ hematopoietic stem cells and CD133+KDR+ endothelial progenitors, independently of potential confounders. The in vivo angiogenic capacity of peripheral blood mononuclear cells significantly increased after hrG-CSF in control subjects without DM, but not in patients with DM. DM was also associated with the inability to upregulate CD26/DPP-4 on CD34+ cells, which is required for the mobilizing effect of granulocyte colony–stimulating factor. Stem and proangiogenic cell mobilization in response to hrG-CSF is impaired in DM, possibly because of maladaptive CD26/DPP-4 regulation. These alterations may hamper tissue repair and favor the development of cardiovascular complications.
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影响因子：
3.7
作者：
Fadini, Gian Paolo;Maruyama, Shoichi;Werner, Nikos
通讯作者：
Werner, Nikos
影响因子：
5.8
作者：
Fadini, G. P.;Albiero, M.;Avogaro, A.
通讯作者：
Avogaro, A.
影响因子：
16.2
作者：
Fadini, Gian Paolo;Boscaro, Elisa;Avogaro, Angelo
通讯作者：
Avogaro, Angelo
影响因子：
39.3
作者：
Fadini, Gian Paolo;Vigili de Kreutzenberg, Saula;Avogaro, Angelo
通讯作者：
Avogaro, Angelo
影响因子：
82.9
作者：
Aicher, A;Heeschen, C;Dimmeler, S
通讯作者：
Dimmeler, S