P88	Mesenchymal stem cells do not automatically participate in neovascularization processes: Indication of different subpopulations?
1K.Jaquet, 1J.Denschel, 1P.Faessler, 2C.Lange, 2A.Zander, 1K-H.Kuck, 1K.Krause
1St. Georg Hospital, Hamburg, DE; 2Bone Marrow Transplantation Center Eppendorf University Hospital, Hamburg, DE.

Background and purpose: The amount of circulating bone marrow (BM) stem cells is too small to give rise to a clinically relevant autoregeneration of heart tissue after myocardial infarction. Recently, BM-derived mesenchymal stem cells (MSC) were discovered which migrate into injured myocardium and participate in the neovascularization process. Among other stem cell subpopulations MSC may be potential candidates for repairing ischemic myocardium via enhancing angiogenesis. Methods: BM was isolated from tibia and femur of Wistar rats (n=13; 8 treated animals/5 controls) and incubated at 37°C and 5% CO<2sub> for 24h. Adherent cells were separated, expanded and transduced for expressing GFP. After a lateral (mini-) thoracotomy and the generation of a 3x6mm cryolesion 2x10<6sup> MSCs were injected into rat myocardium. 5 injections (50µl each) were applied into the borderzone of the ischemic area. Results: After a 10 week follow-up the hearts were excised and analyzed immunohistochemically. Transplanted rMSCs were viable and formed groups within the target tissue. A considerable proportion of Endorem-positive cells seemed to have migrated into the ischemic area. Compared to the control animals (n=5) treated rats (n=8) demonstrated smaller myocardial scars. But, the mechanism causing this effect is not the participation of rMSCs in a neovascularization process. The number of vessels in the ischemic areas of the control group was exactly the same as in the treated animals. But, compared to normal rat myocardium the amount of vessels was twice as high in the injection areas. This might add further substance to the notion that the injury of the myocardium caused by the syringe needle alone can be an adequate stimulus for the induction of angiogenesis. In addition, using an in-vitro angiogenesis assay rMSCs showed a totally different growth behaviour than endothelial cells. Conclusion: 1. Transplanted animals exhibit considerably smaller myocardial scars demonstrating that the remodeling process is reduced. 2. In contrast to others an increased neovascularization is not responsible for the reduction of the myocardial scar size. 3. The existence of different MSC subpopulations exhibiting different angiogenic potential might be the explanation for this finding.

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