Am J Stem Cell 2012;1(2):138-145

Original Article
Prostaglandin E2: a putative potency indicator of the immunosuppressive activity of
human mesenchymal stem cells

Luis A Solchaga, Elizabeth A Zale

BioMimetic Therapeutics, Inc.; Franklin, TN, 37067, USA; University of Chicago, Chicago, IL, 60637, USA

Received March 26, 2012; accepted May 5, 2012; Epub May 18, 2012; Published June 30, 2012

Abstract: Mesenchymal stem cells (MSCs) are non-hematopoietic, pluripotent cells that give rise to stromal cells in the marrow. MSCs
have been shown to be immunsuppressive and have become an attractive therapeutic option for the modulation of undesired immune
responses. Currently, ex vivo expanded human (h)MSCs are being utilized in clinical trials both in the USA and in Europe to treat a variety
of immune disorders. hMSCs need to be harvested, isolated and expanded in culture. This necessary expansion may also result in
decrease or loss of the immunomodulatory potential of hMSCs. Ideally, the intrinsic immunomodulatory activity (potency) of an hMSC
preparation should be assessed prior to its administration. The goal of the experiments described here was to develop a simple potency
assay for the immunomodulatory properties of hMSCs. The immunosuppressive activity of hMSCs conditioned media was tested in
enzyme-linked immunosorbent spot assays (elispot) and the immunosuppressive activity of the conditioned media was correlated with
the concentration of several cytokines present in these conditioned media. The concentration of prostaglandin E2 in the media correlated
with their immunosuppressive activity. The concentration of the other cytokines measured did not correlate with theimmunosuppressive
activity of the media. The dose-response effect could be replicated by adding PGE2 to elispot assays. Furthermore, the
immunosuppressive activity of the conditioned media was inhibitable by a neutralizing anti-PGE2 antibody. These data suggest that
measurement of PGE2 in media conditioned by hMSCs exposed to inflammatory stimuli could be used as a surrogate measure of their
immunosuppressive capacity. These findings need to be confirmed in vitro using different assays of immune function and validated in
vivo to determine the level of correlation of these data with efficacy in pre-clinical models of immune disorders. (AJSC1203001).

Keywords: Mesenchymal stem cell, immunosuppression, prostaglandin E2, cellular therapy, cell culture

Address all correspondence to:
Dr. Luis A Solchaga
Principal Scientist, Research and Development
389 Nichol Mill Lane, Franklin, TN 37067, USA.
Tel: 615-236-4511
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