Advances in mesenchymal stem cell research in sepsis.
BACKGROUND
Sepsis remains a source of morbidity and mortality in the postoperative patient despite appropriate resuscitative and antimicrobial approaches. Recent research has focused upon additional interventions such as exogenous cell-based therapy. Mesenchymal stem cells (MSCs) exhibit multiple beneficial properties through their capacity for homing, attenuating the inflammatory response, modulating immune cells, and promoting tissue healing. Recent animal trials have provided evidence that MSCs may be useful therapeutic adjuncts.


METHODS
A directed search of recent medical literature was performed utilizing PubMed to examine the pathophysiology of sepsis, mechanisms of mesenchymal stem cell interaction with host cells, sepsis animal models, and recent trials utilizing stem cells in sepsis.


RESULTS
MSCs continue to show promise in the treatment of sepsis by their intrinsic ability to home to injured tissue, secrete paracrine signals to limit systemic and local inflammation, decrease apoptosis in threatened tissues, stimulate neoangiogenesis, activate resident stem cells, beneficially modulate immune cells, and exhibit direct antimicrobial activity. These effects are associated with reduced organ dysfunction and improved survival in animal models.


CONCLUSIONS
Research utilizing animal models of sepsis has provided a greater understanding of the beneficial properties of MSCs. Their capacity to home to sites of injury and use paracrine mechanisms to change the local environment to ultimately improve organ function and survival make MSCs attractive in the treatment of sepsis. Future studies are needed to further evaluate the complex interactions between MSCs and host tissues.
Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. dmeldrum@iupui.edu
Todd J
TJ
Wannemuehler
Mariuxi C
MC
Manukyan
Benjamin D
BD
Brewster
Joshua
J
Rouch
Jeffrey A
JA
Poynter
Yue
Y
Wang
Daniel R
DR
Meldrum
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D035843:Biomedical Research / Q000639:trends*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004195:Disease Models, Animal; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology / Q000628:therapy*