bcl-2 tx: Long Live Mesenchymal Stem Cells

Rostock, Germany -

Anti-inflammatory and regenerative abilities of mesenchymal stem cells are well-known. In fact, the first non-hematopoietic clinically approved use of stem cells is most likely to occur with Osiris's mesenchymal stem cell products which are in Phase III of clinical trials.

The important question scientists have to ask themselves is what is the next stem in stem cell application? How can these cells be made more potent?

On the one hand, the combination of stem cells with exogenous drugs will gain interest. Drugs that synergize with stem cells will initially be various growth factors such as G-CSF, M-CSF, EPO, etc. Subsequently, small molecule drugs will be used in combination with stem cells for a wide variety of uses. For example, thalidomide has been demonstrated to selectively expand certain types of stem cells while inhibiting malignant angiogenesis.

In terms of increasing activity of stem cells, the other angle that will be investigated is various manipulations of the stem cells themselves. In a recent paper (Li et al. Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function. Stem Cells. 2007 May 3) the anti-apoptotic protein bcl-2 was transfected into mesenchymal stem cells in order to increase their life-span.

In vitro experiments demonstrated that the bcl-2 transfected mesenchymal stem cells had a reduced rate of basal apoptosis, which is to be expected. What was unexpected was that the cells produced much higher levels of VEGF under hypoxic conditions as compared to the non-transfected cells.

Administration of bcl-2 transfect mesenchymal stem cells in vivo after left anterior descending artery ligation resulted in approximately 20% reduction in infarct size as compared to animals recieving control mesenchymal stem cells. Angiogenesis in the peri-infarct area was higher in the animals recieving transfected mesenchymal stem cells.

Although these experiments suggest a possible benefit for utilization of transfected mesenchymal stem cells, the use of antiapoptotic genes is very dangerous and is not likely to enter clinical trials any time soon.