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Treating Sepsis with Wharton’s Jelly MSCs

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Review of “Treatment with Human Wharton’s Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction” from Stem Cells Translational Medicine by Stuart P. Atkinson

Bacterial infection of wounds, or sepsis, is currently the leading cause of death in intensive care units [1]. As the pathophysiology of sepsis involves complex cytokine and inflammatory responses, treatment with mesenchymal stem cells (MSCs) may provide a tissue protective role [2].

To study this potential protective effect, researchers from the laboratory of Lúcia Andrade (University of São Paulo School of Medicine, Brazil) have applied human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) [3, 4] in a rat model of sepsis. Excitingly, in their new Stem Cells Translational Medicine study, the group shows that WJ-MSCs preserve renal, hepatic, and endothelial function, and so may represent an exciting new treatment option [5].

The authors used cecal ligation and puncture (CLP) to model sepsis in rats, and following administration of WJ-MSCs, survival increased in treated rats (87.5% at 5 days) as compared to untreated mice (55.6%). Increased survival correlated to the preservation of renal function, lower renal injury, lower macrophage infiltration, and lower levels of apoptosis. Furthermore, levels of proinflammatory cytokines and NF-K returned to levels similar to control following WJ-MSC treatment, and endothelial marker expression increased. WJ-MSC also attenuated the loss of Klotho expression, a key marker of sepsis-induced acute kidney injury [6], to a level higher that observed for human adipose-derived MSC treatment.

Meanwhile, the WJ-MSC treatment also preserved liver function, as assessed by the measurement of liver enzyme levels (ALT and AST) and glycogen deposition. These assessments found that WJ-MSC treatment helped to reduce enzyme levels towards that observed in control mice and promoted the deposition of glycogen in the liver (See figure), all suggesting an improvement in liver function.

These exciting findings suggest that WJ-MSCs may be especially suitable for the protection of renal and hepatic function and so may be highly important in the fight against sepsis. Furthermore, the authors posit that Klotho may be an important marker for kidney injury and that Klotho expression may preserve kidney function during sepsis.

References

  1. Jawad I, Luksic I, and Rafnsson SB Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality. J Glob Health 2012;2:010404.
  2. Xu J, Woods CR, Mora AL, et al. Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. Am J Physiol Lung Cell Mol Physiol 2007;293:L131-141.
  3. Romanov YA, Svintsitskaya VA, and Smirnov VN Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells 2003;21:105-110.
  4. Watson N, Divers R, Kedar R, et al. Discarded Wharton jelly of the human umbilical cord: a viable source for mesenchymal stromal cells. Cytotherapy 2015;17:18-24.
  5. Condor JM, Rodrigues CE, Sousa Moreira R, et al. Treatment With Human Wharton's Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction. Stem Cells Transl Med 2016;5:1048-1057.
  6. Hu MC, Shi M, Zhang J, et al. Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective. Kidney Int 2010;78:1240-1251.