Fighting sepsis with stem cells

Stem cells are usually thought of as possible
treatments for diseases like spinal cord injuries or type I diabetes, in which cells need to
be replaced. But increasing evidence suggests they may
be able to help with sepsis — a life-threatening complication of infection. Sepsis is one of the most deadly and expensive
syndromes, killing a quarter of a million people and incurring 20 billion dollars in
hospital costs every year in the United States alone. Classically, sepsis has been thought of as
a problem of an overactive immune system. As immune cells respond to infection, they
unleash a torrent of inflammatory cytokines, or what’s called a cytokine storm, which
can lead to organ failure. But recently, doctors have discovered that
sepsis is more complicated, and if someone survives this early hyper-inflammatory stage,
they are still at risk of succumbing later, when the syndrome switches over to being immune
suppressive. Currently, there are no treatments beyond
antibiotics, which need to be given early to be fully effective. Multipotent stromal, or connective tissue,
cells known as mesenchymal stem cells, may be ideally suited to fighting sepsis. Preclinical studies have found that they can
strengthen the immune response to pathogens while limiting host damage, and boosting tissue
repair. And because the cells have few antigen-presenting
molecules on their surface, they are less likely to be rejected. This means that they can be taken from a donor,
stored, and transplanted into another patient, much like we do with blood products today. In animal models of sepsis, researchers have
found that stem cells are protective and operate through a variety of mechanisms. The cells reduce bacterial growth with antimicrobial
peptides, and activate macrophages to phagocytose and kill pathogens. At the same time, stem cells keep the immune
response in check by promoting T regulatory cells, and producing the right mix of cytokines
and chemokines to keep neutrophils from spreading into healthy tissues. The cells also pass mitochondria on to the
epithelium to reduce injury in the lung. These studies demonstrate the potential for
stem cells to radically improve sepsis treatment, but substantial hurdles remain. Clinical trials are mostly just getting started,
and those in progress or completed for other diseases have struggled to replicate some
of the animal results, indicating the need for caution. Complicating things is the fact that no one
marker can identify mesenchymal stem cells, and they’re a heterogenous population anyway. We don’t yet know which sources may be better
at fighting sepsis, or what the best doses are and when to give them. Finally, while the cells appear mostly safe,
there are still concerns about infusional toxicity and whether they can contribute to
cancer. More work is needed to investigate what goes
on in the body during sepsis, and whether stem cells will ultimately be an effective
treatment for one or more subtypes of the condition.

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