Impact of age on the efficacy of bone marrow mononuclear cell transplantation in experimental stroke

Cerebral ischemia is one of the leading causes for mortality and disability in industrialized countries, and its treatment is seriously restricted by a tight therapeutic time frame. Less than 5% of stroke patients receive thrombolysis, primarily due to delayed clinical presentation [1]. Consequently, one of the main goals of modern stroke research is an extension of the therapeutic time window. Cell based therapies might fulfil this expectation, since cells are suspected to modulate protective and restorative effects even days after the onset of brain ischemia [2]. Bone marrow derived mononuclear cells (BM MNC) are promising candidates for acute stroke treatment, since these cells can be harvested and re-transplanted acutely in an autologous fashion [3]. An open-label prospective study just recently showed that bone marrow harvest and reinfusion of autologous MNCs in patients with acute middle cerebral artery ischemic stroke is safe and feasible [4].BM MNC transplantation in experimental models of brain ischemia and spinal cord injury resulted in a significantly improved functional recovery [5-7], and the therapeutic time window for these effects seems to be between 3 h-72 h after stroke onset [8]. However, most of the preclinical trials have been performed in young or middle-aged, healthy laboratory animals - even though age and hypertension are crucial risk factors for stroke [9], and the susceptibility of the ischemic brain for cell-based therapies might be altered with age. Beyond that, age and comorbidities have to be particularly considered if autologous approaches are intended, since not only the receiving tissue but also the donor tissue (i.e. the bone marrow) is subjected to aging processes and might be altered in its functionality. In the present study we aimed to analyze the effect of age on the efficacy of BM MNC transplantation for cerebral ischemia. For this, we investigated the therapeutic efficacy of human BM MNCs obtained from aged or young donors i