Dual-modal magnetic resonance and photoacoustic tracking and outcome of transplanted tendon stem cells in the rat rotator cuff injury model

Abstract

Stem cells have been used to promote the repair of rotator cuff injury, but their fate after transplantation is not clear. Therefore, contrast agents with good biocompatibility for labeling cell and a reliable technique to track cell are necessary. Here, we developed a micron-sized PLGA/IO MPs to label tendon stem cells (TSCs) and demonstrated that PLGA/IO MPs were safe and efficient for longterm tracking of TSCs by using dual-modal MR and Photoacoustic (PA) imaging both in vitro and in rat rotator cuff injury. Moreover, TSCs improved the repair of injury and the therapeutic effect was not affected by PLGA/IO MPs labeling. We concluded that PLGA/IO particle was a promising dual-modal MR/PA contrast for noninvasive long-term stem cell tracking. Rotator cuff injury is one of the most common shoulder diseases, which occur most often in people who repeatedly perform overhead motions in their jobs or sports 1. The conventional therapies used for rotator cuff injury include analgesics, anti-inflammatory drugs, physiotherapy, steroids injection, and surgical repair 2. In fact, conservative treatments usually show short-term pain relief but lack long-term efficacy 3. Despite advances in surgical treatment options, the failure rates of rotator cuff repairs were still as high as 20% 4. In recent years, stem-cell-driven regeneration is gaining increased attention, and mesenchymal stromal cells (MSCs) have been widely applied for the treatment of rotator cuff tears on the basis of their self-renewal, clonogenicity, and multidifferentiation potential 5-12. But Mohammad et al. found that intra-synovial implantation of marrow-derived MSCs did not promote tendon healing in ovine deep digital flexor tendon injury model 12. While, tendon stem cells (TSCs) display high clonogenecity, cell proliferation, and tenogenic-differentiation potential compared to bone marrow mesenchymal stromal cells since Bi et.al firstly identified them in 2007, suggesting that they could be a better cell source for tendon regeneration 13. To develop effective TSCs therapies, it is imperative to label and track the administrated cells, preferably in a noninvasive manner with high efficiency. Recently, optical imaging, radionuclide imaging, magnetic resonance imaging (MRI), ultrasound (US), photoacoustic (PA) imaging and computed tomography (CT), have been widely used for cell tracking 14-19. However, each individual imaging has its own advantages and limitations. Optical imaging suffers from shallow penetration depth and phototoxicity, and radionuclide imaging has poor spatial resolution and rapid decay of radioisotopes 20,21. MRI, as the gold standard stem cell tracking modality, has high spatial resolution and deep penetration but has a relatively poor temporal resolution 19,22. While, PA have excellent temporal resolution but suffer from poor penetration depth 16,23. Therefore, nanoparticles based dual-/multi-modal imaging modalities that allow long-term tracking of stem cells with nontoxicity and good biocompatibility are need 24,25 .