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 Blood, 30 April 2009, Vol. 113, No. 18, pp. 4197-4205.
Prepublished online as a Blood First Edition Paper on November 25, 2008; DOI 10.1182/blood-2008-09-176198.

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Submitted September 10, 2008
Accepted November 2, 2008

Concentration dependent inhibition of angiogenesis by mesenchymal stem cells

Keishi Otsu, Shonit Das, Sandra D. Houser, Sadiqa K Quadri, Sunita Bhattacharya, and Jahar Bhattacharya*

Lung Biology Laboratory, College of Physicians & Surgeons, Columbia University, St. Luke's Roosevelt Hospital Center, New York, NY, United States

* Corresponding author; email: jb39{at}columbia.edu.

Mesenchymal stem cells (MSC), which potentially transdifferentiate into multiple cell types, are increasingly reported to be beneficial in models of organ system injury. However, the molecular mechanisms underlying interactions between MSC and host cells, in particular endothelial cells (EC) remain unclear. We show here in a Matrigel angiogenesis assay, that MSC are capable of inhibiting capillary growth. Following addition of MSC to EC-derived capillaries in Matrigel at EC:MSC ratio of 1:1, MSC migrated towards the capillaries, intercalated between EC, established Cx43-based gap junctional intercellular communication (GJC) with EC and increased production of reactive oxygen species (ROS). These events led to EC apoptosis and capillary degeneration. In an in vivo tumor model, direct MSC inoculation into subcutaneous melanomas induced apoptosis and abrogated tumor growth. Thus, our findings show for the first time that at high numbers, MSC are potentially cytotoxic and that injected locally in tumor tissue they might be effective anti-angiogenesis agents suitable for cancer therapy.


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Related Article in Blood Online:

Mesenchymally "stemming" angiogenesis
Michael A. Matthay
Blood 2009 113: 4131-4132. [Full Text] [PDF]



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M. A. Matthay
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Blood, April 30, 2009; 113(18): 4131 - 4132.
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