(W1097) ANGIOGENESIS PROVIDES A FUNDAMENTAL SUPPORT FOR HOMING OF EXOGENOUSLY INFUSED ALLOGENEIC AD-MSCS TO THE INJURED BRAIN TISSUE POST ACUTE ISCHEMIC STROKE
Abstract: Mesenchymal stromal cells (MSCs) are mainstay of cell therapy for currently unmet disease conditions. MSCs need homing to the injured tissue in order to promote tissue regeneration. However, the mechanism by which MSCs home to their action site remains elusive. This study was undertaken to specifically address this fundamental issue for MSCs clinical application. Rats were subjected to a permanent middle cerebral artery occlusion (pMCAO) surgery to produce an acute ischemic brain iry. Allogeneic AD-MSCs were infused via tail vein at 6, 24, or 36 hrs post the pMCAO surgery. The best recovery of brain structure and function, as judged by balance beam test, left forelimb placement test and 2,3,5-triphenyltetrazolium chloride (TTC) staining of injured brain tissue, from the acute ischemia was found at the time of AD-MSCs administration at 24 or 36 hrs, not 6 hrs, post the surgery. This time period was well correlated with the peak time period of self-defense motivated angiogenesis in the injured brain tissue, as determined by co-staining of CD31 and BrdU. The infused AD-MSCs were found to be condensed in the highly angiogenesis area. In this area, AD-MSCs were colocalized with newly generated vascular endothelial cells. Prevention of endothelial cell regeneration blocked the homing of AD-MSCs to the injured brain tissue and diminished the therapeutic effect of AD-MSCs on acute ischemic stroke. This study thus confirmed that the therapeutic efficacy of MSCs depends on the homing of these cells to the injured site, and found that MSCs homing is angiogenesis-dependent. Therefore, promotion of angiogenesis prior to MSCs administration would significantly enhance the efficacy of MSC therapy.
