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糖尿病作为一种动员不佳的情况。

Diabetes mellitus as a poor mobilizer condition.

机构信息

Department of Medicine, University of Padova, 35128 Padova, Italy; Venetian Institute of Molecular Medicine, 35128 Padova, Italy.

Washington University School of Medicine, St Louis, MO, United States.

出版信息

Blood Rev. 2018 May;32(3):184-191. doi: 10.1016/j.blre.2017.11.002. Epub 2017 Nov 8.

Abstract

Hematopoietic stem cell (HSC) transplantation in an effective and curative therapy for numerous hematological malignancies. Mobilization of HSCs from bone marrow (BM) to peripheral blood (PB) followed by apheresis is the gold standard for obtaining HSCs for both autologous and allogeneic stem cell transplantation. After administration of granulocyte-colony stimulating factor (G-CSF), up to 30% of patients fail to mobilize "optimal" numbers of HSCs required for engraftment. This review summarizes the current experimental and clinical evidence that diabetes mellitus is a risk factor for poor mobilization. Diabetes causes a profound remodeling of the HSC niche, resulting in impaired release of HSCs. Experimental studies indicate that hyperglycemia hampers regulation of CXCL12 and clinical studies suggest that diabetes impairs HSC mobilization especially in response to G-CSF, but less to plerixafor. Understanding further the biochemical alterations in the diabetic BM will provide insights into future therapeutic strategies to reverse the so-called "diabetic stem cell mobilopathy".

摘要

造血干细胞(HSC)移植是治疗许多血液系统恶性肿瘤的有效方法。动员造血干细胞从骨髓(BM)到外周血(PB),然后通过单采术获得自体和异基因干细胞移植所需的 HSCs,这是金标准。在粒细胞集落刺激因子(G-CSF)给药后,多达 30%的患者未能动员出“最佳”数量的 HSCs 以进行植入。这篇综述总结了目前的实验和临床证据,表明糖尿病是动员不良的危险因素。糖尿病导致 HSC 龛的深刻重塑,导致 HSC 释放受损。实验研究表明,高血糖会干扰 CXCL12 的调节,临床研究表明,糖尿病会损害 HSC 的动员,尤其是对 G-CSF 的反应,但对plerixafor 的反应较少。进一步了解糖尿病 BM 中的生化改变将为未来的治疗策略提供深入了解,以逆转所谓的“糖尿病干细胞动员病”。

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