Mr Imaging Evaluation of Stem Cell/ Magnetic Nanoparticle Composite in the Target Therapy against Focal Cerebral Ischemia in Rat

Cerebrovascular disease is ranked the third leading cause of death in Taiwan and is the most common cause of disability in the world. Until now the only documented effective treatment for acute ischemic stroke is intravenous injection of recombinant tissue plasminogen activator (rt-PA). Although intravenous administration of rt-PA is reported effective, the narrow therapeutic time window and its limited treatment in less than 10% stroke patients restrict its application. At present, there is no other effective treatment to improve clinical outcome after acute stroke. The cardinal features of stem cells are multipotency and self-renewal. They can be derived from many human tissues and can differentiate into various types of mature cells, including neuron, cardiomyocyte under appropriate condition. Transplantation of stem cell has been reported to improve neurological deficits in ischemic animal model. However, there is challenge to trace the donor cells and determine the effectiveness of stem cell in the target region. Magnetic resonance (MR) imaging can offer a effective image window, good temporal and spatial resolution and fine signal intensity contrast, and can be used as a good tracing tool to monitor stem cells in vivo. The application of nanotechnology in life sciences offers the potential to study biological systems and to solve medical problems that affect patients. Significant progress has been achieved over the past decades leading to, for example, the approval of nanoformulations for delivering drugs to tumors and other diseased sites. In the present study, we wish to create a stem cell tracking and targeting system by conjugating umbilical cord-derived mesenchymal stem cell, bone marrow mesenchymal stem cell and induced pluripotent stem cell with magnetic nanoparticles to produce different stem cell/ magnetic nanoparticle composite and compare their effectiveness against ischemic injury. Extracorporeal magnetic field will be manipulated to target these composites to the ischemic site, and magnetic nanoparticle will be used as a contrast agent for MR imaging to study its body distribution and biocompatibility. We will also produce thermo-responsive stem cell/ magnetic nanoparticle composite and conjugate with neurotrophic factor, statin or other anti-thrombotic medications. The release of neurotrophic factor, statin or other drugs from the thermo-responsive composite can be controlled using a high radio frequency induced heating machine at the ischemic lesion to reinforce the effect of stem cell. To evaluate the feasibility of the present study, we will use serial MR imaging to trace the stem cell/ magnetic nanoparticle composites for its local distribution and analyze the MR parameters of cerebral blood flow (CBF), apparent diffusion coefficient (ADC), susceptibility-weighted imaging (SWI) and T2-weighted imaging in ischemic lesion. We will also use immunohistochemistry to detect the pathological change of brain cells, to insure the targeting effect of the composites and to study the possible protective mechanism of these composites against ischemic injury. The present study will investigate the effect of target treatment of stem cell/ magnetic nanoparticle against ischemic injury in animal model and evaluate the future applicability in human stroke.

Project ID:PC10107-0055
External Project ID:NSC101-2314-B182A-100