Mobilization of Stem and Progenitor Cells in Septic Shock Patients

Urszula Zielińska-Borkowska,Małgorzata Mikaszewska-Sokolewicz,Barbara Dołęgowska,Jerzy Kawiak,Grażyna Hoser,Tomasz Skirecki,Jarosław Czubak,Marlena Godlewska

doi:10.1038/s41598-019-39772-4

Abstract

Septic shock is associated with multiple injuries to organs and tissues. These events may induce the regenerative response of adult stem cells. However, little is known about how endogenous stem cells are modulated by sepsis. This study analyzed the circulation of hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs) and very small embryonic-like stem cells (VSELs) in the peripheral blood of patients with septic shock. Thirty-three patients with septic shock and twenty-two healthy control subjects were enrolled in this prospective observational study. Blood samples were collected on the first, third and seventh days of septic shock. Populations of stem cells were analyzed by flow cytometry. Chemotactic mediators were analyzed by HPLC and ELISA. Populations of early HSCs (Lin-CD133+CD45+ and CD34+CD38−) were mobilized to the peripheral blood after an initial decrease. Mobilized HSCs showed significantly increased expression of Ki-67, a marker of cell proliferation. Circulating EPCs and VSELs were mobilized to the blood circulation upon the first day of sepsis. Patients with a greater number of Lin-CD133+CD45+ HSCs and Lin-CD34+CD45− VSELs had a significantly lower probability of 60-day survival. The concentration of CXCL12 was elevated in the blood of septic patients, while the concentration of sphingosine-1-phosphate was significantly decreased. As an emergency early response to sepsis, VSELs and EPCs were mobilized to the peripheral blood, while the HSCs showed delayed mobilization. Differential mobilization of stem cell subsets reflected changes in the concentration of chemoattractants in the blood. The relationship between the probability of death and a large number of HSCs and VSELs in septic shock patients can be used as a novel prognostic marker and may provide new therapeutic approaches.

Highlights

Adult organisms contain a variety of stem and progenitor cells that are responsible for the continuous renewal and regeneration of damaged tissues
The frequency of circulating CD34+CD38− hematopoietic stem cells (HSCs) was significantly decreased on the days 1 and 7 of sepsis compared to the healthy controls (Supplemental Table 2)
The proper identification of very small embryonic-like stem cells (VSELs) stem cells requires strict gating criteria, which results in the ability to observe and analyze this rare population of CD45-negative stem cells that are smaller than the CD45+ HSCs (Fig. 1A–D)[23]

Summary

Introduction

Adult organisms contain a variety of stem and progenitor cells that are responsible for the continuous renewal and regeneration of damaged tissues. Bone marrow hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are responsible for maintaining adult hematopoiesis[3]. Aside from HSCs, bone marrow contains other stem cell populations, such as endothelial progenitor cells (EPCs) and primitive very small embryonic-like stem cells (VSELs), which have the potential to differentiate into multiple cell types, including hematopoietic cells[10,11,12]. Due to the specific imprinting pattern of the insulin growth factor signaling genes, these cells are activated in a strictly regulated manner and have been hypothesized to contribute to the tissue renewal and regeneration[13]. We conducted a study aimed at evaluating the circulation of different stem cell populations during septic shock

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Discussion

Conclusion