Visualizing the Fate of Intra‐Articular Injected Mesenchymal Stem Cells In Vivo in the Second Near‐Infrared Window for the Effective Treatment of Supraspinatus Tendon Tears

Abstract

Mesenchymal stem cells (MSCs) are capable of exerting strong therapeutic potential for the treatment of supraspinatus tendon tear. However, MSC therapy remains underutilized and perhaps underrated due to the limited evidence of dynamic visualization of cellular behavior in vivo. Here, second near‐infrared fluorescence imaging with biocompatible PbS quantum dots (QDs) provides a cellular migration map and information on the biodistribution and clearance processes of three densities of intra‐articularly injected, labeled MSCs to treat supraspinatus tendon tear in mice. Intra‐articular injection avoids entrapment of MSCs by filter organs and reduces the QD‐induced organ toxicity. Notably, the MSCs share a similar migration direction, but the moderate density group is somewhat more efficient, showing the longest residence time and highest cell retention rate around the footprint during the repair stage. Furthermore, quantitative kinetic investigation demonstrates that labeled MSCs are cleared by feces and urine. Histomorphometric analysis demonstrates that the moderate density group achieves maximum therapeutic effect and labeled MSCs do not induce any injury or inflammation to major organs, which suggests that administration of too many or few MSCs may decrease their effectiveness. Such an imaging approach provides spatiotemporal evidence for response to MSC therapy in vivo, facilitating the optimization of MSC therapy.

A Translational Porcine Model for Human Cell–Based Therapies in the Treatment of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Injury

“…Although the authors did not evaluate the survival of these human MSCs within the joint space, they were able to demonstrate reduced pain and decreased cartilage damage among animals treated with human MSCs as compared with controls. Yang et al 58 characterized the biodistribution and distant major organ effects (ie, an assessment of toxicity and off-target effects) of murine MSCs delivered intra-articularly using a murine model of rotator cuff tear. Although the therapeutic cells in this study were not xenogeneic or transgenic cells and the intra-articular delivery of therapeutic cells in the setting of a supraspinatus repair is quite different than that in a knee joint (which has undergone a multilayered closure after arthrotomy), Yang et al did provide evidence that therapeutic MSCs can be cleared in vivo via the renal and gastrointestinal systems and that these cells exhibit no apparent inflammatory effects or toxicity on distant major organs.…”

Recent Progress in NIR-II Contrast Agent for Biological Imaging

“…Tracking the transplanted stem cells in vivo to provide evidence for therapy and promote the optimization of therapy Yang et al, 2019 AgInTe 2 QDs 700 nm/between 1,095 and 1,160 nm (excitation/emission)…”

Hematological patterns and histopathological assessment of Miniature Pigs in the experiments on human mesenchymal stem cell transplantation

“…These results indicated that there were no immune rejection reactions by the lymphoid organs when human MSCs were. It had been reported that after transplantation, most MSCs are filtered by liver, kidney and lung 40 . Keeping these things in mind, in the present study, we performed H&E staining of these organs and they did not show any abnormal findings.…”