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Related Concept Videos

Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

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Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
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Related Experiment Video

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Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
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Human mesenchymal stromal cells decrease mortality after intestinal ischemia and reperfusion injury.

Troy A Markel1, Trevor D Crafts1, Amanda R Jensen1

  • 1Section of Pediatric Surgery, Department of Surgery, Riley Hospital for Children at Indiana University Health, The Indiana University School of Medicine, Indianapolis, Indiana.

The Journal of Surgical Research
|July 30, 2015
PubMed
Summary
This summary is machine-generated.

Human bone marrow-derived mesenchymal stromal cells (BMSCs) significantly reduced mortality in intestinal ischemia/reperfusion (I/R) injury. This cellular therapy enhanced survival by modulating the systemic inflammatory response, not by improving tissue histology.

Keywords:
InflammationIntestinal ischemiaMesenchymal stem cellsMortalitySurvival

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Stem Cell Transplantation in an in vitro Simulated Ischemia/Reperfusion Model
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Area of Science:

  • Regenerative Medicine
  • Gastroenterology
  • Immunology

Background:

  • Intestinal ischemia/reperfusion (I/R) injury poses a significant clinical challenge.
  • Cellular therapy, particularly using bone marrow-derived mesenchymal stromal cells (BMSCs), is a promising therapeutic strategy.
  • Previous studies suggest BMSCs can mitigate I/R injury, but the underlying mechanisms require further elucidation.

Purpose of the Study:

  • To investigate the therapeutic potential of human BMSCs (hBMSCs) in a murine model of intestinal I/R injury.
  • To compare the effects of hBMSCs versus keratinocytes on mortality, inflammation, and tissue repair.
  • To determine if hBMSC therapy alters the expression of growth factors and inflammatory mediators in the intestine and liver.

Main Methods:

  • In vitro analysis of hBMSCs and keratinocytes stimulated with inflammatory agents or hypoxia.
  • In vivo study using a murine model of superior mesenteric artery occlusion for intestinal I/R.
  • Administration of hBMSCs or keratinocytes via intraperitoneal injection immediately post-ischemia.
  • Assessment of mortality, intestinal and hepatic inflammatory markers, growth factors, and histology at 6 hours and 7 days post-reperfusion.

Main Results:

  • hBMSCs produced higher levels of beneficial growth factors (e.g., VEGF) and lower pro-inflammatory mediators compared to stimulated keratinocytes in vitro.
  • Intraperitoneal administration of hBMSCs significantly reduced mortality from 70% to 10% in the I/R model (P=0.004), while keratinocytes showed no benefit.
  • hBMSC therapy led to decreased pro-inflammatory mediators (e.g., MIG, IP-10, G-CSF) in the liver and altered chemokine profiles in the intestine, despite no significant improvement in histologic damage.

Conclusions:

  • Human BMSCs possess inherent properties that promote survival following intestinal I/R injury.
  • Direct application of hBMSCs post-ischemia markedly decreases mortality, suggesting a potent therapeutic effect.
  • The survival benefit of hBMSC therapy appears to be mediated by modulation of the systemic inflammatory response rather than direct tissue repair.