Instant Stem Cell Labeling with a new Microfluidic Device Every year, osteoarthritis accounts for 44 million outpatient visits and 700,000 knee-replacement procedures. Early repair of cartilage defects can prevent further deterioration of the joint and the need for an artificial joint prosthesis. Adipose fat derived stem cells (ADSC) are increasingly being used for cartilage-repair. ADSC can be easily harvested from the patient's own fat depots and implanted into cartilage defects. However, cartilage repair outcomes of ADSC grafts vary greatly between different patients. We developed an imaging test for in vivo tracking of ADSC in order to diagnose successful or unsuccessful engraftment: We label ADSC with iron oxide nanoparticles, which can be detected with MRI. We have shown that an early loss of the iron signal in the cartilage defect correlates with loss of the therapeutic cells and incomplete cartilage repair outcomes. This new imaging test is in principle directly translatable to the clinic. However, we faced an organizational challenge: In a clinical setting, ADSC harvest and transplantation occur in one single surgery. This makes it impossible to label ADSC with nanoparticles through classical cell culture techniques in the laboratory. To solve this problem, we developed a novel microfluidic device, which provides highly efficient labeling of ADSC with nanoparticles through cell volume exchange for convective transfer (CEVT). The goal of our project is to test the ability of this new microfluidic device to label ADSC with ferumoxytol nanoparticles within 15 minutes or less such that the labeled cells can be detected with magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). We are uniquely positioned to pursue this goal because our team members combine decades of experience in microfluidic device fabrication, stem cell labeling with nanoparticles, in vivo stem cell tracking and clinical applications of ADSC for arthritis treatment. In a two-step approach, we will first optimize the cellular nanoparticle uptake and time-efficiency of the labeling process. Next, we will evaluate if ADSC, labeled with ferumoxytol in the new microfluidic device, will provide significant MRI and MPI signal. If successful, these studies will directly lead to clinical translation, accelerate the detection of ADSC grafts which are at risk for unsuccessful cartilage repair outcomes, and ultimately, improve morphological and functional reconstitution of arthritic joints.
Adipose fat derived stem cells (ADSC) are increasingly being used for repair of cartilage defects in arthritic joints. The goal of our project is to test the ability of a new microfluidic device to instantly label ADSC with iron oxide nanoparticles such that the labeled cells can be detected with medical imaging techniques. Instant stem cell labeling enables stem cell harvest, labeling and transplantation in one surgery and facilitates diagnoses of successful or unsuccessful ADSC engraftment on imaging exams.
