Platelet-rich plasma (PRP) contains a multitude of growth factors in physiological proportions, which is an appealing benefit compared to using isolated growth factors. However, the specific targeting of therapeutic agents to sites of tissue damage in vivo is a major challenge that limits the success in delivering growth factors, PRP, or even stem cell therapy. Human mesenchymal stem cells (hMSCs) can have a beneficial effect on injured and diseased skeletal muscle, but a concern with standard delivery is getting them to, and keeping them at, the targeted tissue. This proposal will use fluorescent iron oxide-based superparamagnetic nanoparticles (NPs), which can be visualized by both MRI (in vivo) and fluorescence microscopy (after harvesting). The overall goal of this proposal is to target platelet and hMSCs to a site of musculoskeletal injury in vivo by exploiting the magnetic properties of NPs. Cells can be labeled with a variety MRI contrast agents and detected in vivo following local or systemic injection. Recent work shows that: a) cells readily take up NPs and can be mobilized in vitro by the application of magnetic force, and b) platelets readily take up the NPs, without complex cellular labeling strategies that rely on the overexpression of specific receptors or the conjugation to specific ligands. We will build on these two findings to develop an in vivo therapeutic intervention. We propose that the location of PRP/hMSCs can be controlled by use of a surface magnet; thus allowing movement of platelets/cells to a desired site, clustering to enrich the area with growth factors, and preventing the premature loss at the site of injury. Musculoskeletal injuries are one of the most common complaints treated by physicians; they account for the majority of all sports-related injuries as well as a significant proportion of low back pain. We will use a cellular -- organ system -- clinical approach in studying this novel application to promote regeneration at sites of tissue damage. The focus of this proposal is on platelets/hMSCs, however this technology has exciting applications in a variety of cells and for a range of pathologies.
Platelet-rich plasma (PRP) contains a multitude of growth factors in physiological proportions, which is an appealing benefit compared to using isolated growth factors, and human mesenchymal stem cells (hMSCs) have been shown to have regenerative potential in muscle and bone; but the specific targeting of such therapeutic agents to sites of tissue damage in vivo is a major challenge. This proposal will use iron-oxide nanoparticles (NPs) to target platelets and hMSCs to a site of musculoskeletal injury in vivo by exploiting the magnetic properties of NPs. We propose that the location of platelets and regenerative cells can be controlled by use of a surface magnet; thus allowing movement of platelets/cells to a desire site, clustering to enrich the area with growth factors, and preventing the premature loss at the site of injury. This technology has exciting applications beyond this use, including, but not limited to, tracking and positioning stem cells, anti-inflammatory agents, and even packaged cDNA for use in viral transfection.
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| Iyer, Shama R; Xu, Su; Stains, Joseph P et al. (2017) Superparamagnetic Iron Oxide Nanoparticles in Musculoskeletal Biology. Tissue Eng Part B Rev 23:373-385 |
