Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease

Journal of Translational Medicine

Antonio Gasbarrini³  Luigi Maria Larocca⁴  Giovanni Cammarota³  Tonia Cenci⁴  Giuseppina Bonanno⁵  Luca Di Maurizio³  Federico Barbaro³  Gianluca Ianiro³  Immacolata Alessia Cazzato²  Mariachiara Campanale³  Valentina Cesario³  Lucrezia Laterza³  Sergio Rutella¹  Anna Chiara Piscaglia³ 

[1] Division of Translational Medicine, Clinical Research Centre, Sidra Medical and Research Centre, Burj Doha, 8th Floor, Doha, Qatar;Endoscopy and Gastroenterology Unit, “S. Caterina Novella” Hospital, Galatina, Lecce, Italy;Institute of Internal Medicine and Gastroenterology, “A. Gemelli” Hospital, Catholic University, Rome, Italy;Institute of Pathology, “A. Gemelli” Hospital, Catholic University, Rome, Italy;Institute of Gynecology, “A. Gemelli” Hospital, Catholic University, Rome, Italy

关键词: Lgr5;    CD133;    CD34;    Mucosal repair;    Intestinal stem cells;    Coeliac disease;    Stem cells;   

Others  :  1221468
DOI  :  10.1186/s12967-015-0591-0

 received in 2015-05-27, accepted in 2015-06-30,  发布年份 2015

【 摘 要 】

Background

The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD.

Methods

Thirty-one CD patients and 7 controls were enrolled. Circulating CD133 ⁺and CD34 ⁺HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3 ⁺lymphoid cells) and the putative ISC compartment (CD133 ⁺and Lgr5 ⁺epithelial cells).

Results

At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal.

Conclusions

In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission.

【 授权许可】

   
2015 Piscaglia et al.

【 图 表 】

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