Mesenchymal Stem Cells Augmented by Estrogen

Indianapolis, Indiana -

Mesenchymal stem cells, have very potent therapeutic potential because they can be used in an allogeneic manner, they can differentiate into many new types of tissue, and they produce numerous growth factors.  Mesenchymal stem cells have been demonstrated in non-clinical systems to be effect in regenerating injured vertebral discs,  treatment of diabetes, and reversing liver failure.

It is known that mesenchymal stem cells from women generally work better than from men when it comes to regenerative functions.  Additionally, estrogen has interesting properties that may provide rationale for assessing stem cell activating activities.  For example, it is capable of augmenting telomerase activity.  In a recent study (Erwin et al. Estradiol-Treated Mesenchymal Stem Cells Improve Myocardial Recovery After Ischemia. J Surg Res. 2008 Mar 13) the effect of estrogen treatment of mesenchymal stem cells before administration was assessed.  As output the investigators sought to determin whether the treated mesenchymal stem cells had better ability to stimulate therapeutic angiogenesis in an infarct model as compared to control treated mesenchymal stem cells.

Estrogen-treated or control treatment male mesenchymal stem cells (1 million) were assessed for growth factor production in vitro, as well as for therapeutic activity in vivo be injection via the transcoronary route into rats subsequent to induction of ischemia.  In investigators observed that estrogen pretreatment induced almost a doubling in VEGF production, as well exerted a potent therapeutic effect in vivo.  

These data are very relevant since clinically mesenchymal stem cells are being used for treatment of post infarct remodelling in clinical trials.  A recently completed trial demonstrated statistically significant improvement in left ventricular ejection fraction by intravenous allogeneic mesenchymal stem cell administration.  The issue is how to actually optimize activity of the stem cells either before injection by pretreatment with agents, as performed in this study, or after the injection by providing proper nutrients or adding systemic growth factors to recipients.  While on the topic of mixing stem cell therapy with other agents, it may be of interest to know that even some cancer drugs such as Velcade, alter activity of stem cells administered in vivo.