Mobilization of Stem and Progenitor Cells in Septic Shock Patients

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.

Spinal cord injury causes chronic bone marrow failure

“…Bone marrow failure develops within 72 h post-injury and persists until at least 1-month post-injury. To determine whether failed bone marrow in SCI mice is able to respond to physiologically relevant stimuli, mice with chronic SCI were challenged with endotoxin (1 mg kg −1 ; lipopolysaccharide (LPS)), a potent inducer of HSPC proliferation and mobilization 34 , 49 – 51 . Mito-luc transgenic and C57BL/6J (wild-type) mice were injected with LPS daily for 3 days beginning 6 weeks after T3 transection SCI or sham surgery (Fig.…”

Similar Population of CD133+ and DDX4+ VSEL-Like Stem Cells Sorted from Human Embryonic Stem Cell, Ovarian, and Ovarian Cancer Ascites Cell Cultures: The Real Embryonic Stem Cells?

“…These cells were first discovered by the research group of Ratajczak [1,2] and further explored by several other groups in bone marrow [3,4,5,6,7,8], umbilical cord blood [9,10,11,12], peripheral blood [13,14], uterine endometrium [15], testis [16], retina [17] and bone [18] in humans and rodents. VSELs are proposed to originate in the embryonic epiblast during development [19,20], mobilized into the peripheral blood under inappropriate conditions (e.g., stroke, myocardial ischaemia, skin burn injury, septic shock, brain injury, Crohn’s disease) to regenerate the tissues and organs [21,22,23,24,25,26], and proposed to be able to regenerate organs, such as the pancreas, brain, lung, liver or heart, by transplantation [27,28,29,30,31]. Under inappropriate conditions in the body, these cells may form tumours [32] and are involved in the manifestation of ovarian cancer.…”

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications

“…Sepsis syndrome and septic shock represent major health problems worldwide and they are leading causes of death in hospitalized patients due to their association with high rates of morbidity and mortality in the absence of effective therapy [48][49][50][51]. Sepsis is a potentially lethal syndrome that can develop following an infection in which a breakdown in the immune homeostasis results in both proinflammatory and anti-inflammatory mechanisms that become uncoupled from normal regulation [50].…”

“…The inflammatory-driven maladaptive response induces disruption of endothelial and epithelial barriers, thus resulting in organ dysfunction. However, the host responds to sepsis by stimulating the proliferation of HSCs in the BM or by activating emergency hematopoiesis in an attempt to counteract the effects of sepsis on the function of multiple body organs [51]. Septic shock is a devastating complication of uncontrolled bacterial infection that carries a mortality rate of 20-50% [50,52].…”