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Increasing the Efficacy of Stem Cell Therapy via Triple-Function Inorganic Nanoparticles.

ABSTRACT: Stem cell therapy in heart disease is challenged by mis-injection, poor survival, and low cell retention. Here, we describe a biocompatible multifunctional silica-iron oxide nanoparticle to help solve these issues. The nanoparticles were made via an in situ growth of Fe₃O₄ nanoparticles on both the external surfaces and pore walls of mesocellular foam silica nanoparticles. In contrast to previous work, this approach builds a magnetic moiety inside the pores of a porous silica structure. These materials serve three roles: drug delivery, magnetic manipulation, and imaging. The addition of Fe₃O₄ to the silica nanoparticles increased their colloidal stability, T₂-based magnetic resonance imaging contrast, and superparamagnetism. We then used the hybrid materials as a sustained release vehicle of insulin-like growth factor-a pro-survival agent that can increase cell viability. In vivo rodent studies show that labeling stem cells with this nanoparticle increased the efficacy of stem cell therapy in a ligation/reperfusion model. The nanoparticle-labeled cells increase the mean left ventricular ejection fraction by 11 and 21% and the global longitudinal strain by 24 and 34% on days 30 and 60, respectively. In summary, this multifunctional nanomedicine improves stem cell survival via the sustained release of pro-survival agents.

SUBMITTER: Chen F

PROVIDER: S-EPMC8106804 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Osteoporosis develops with high prevalence in both postmenopausal women and hypogonadal men. Osteoporosis results in significant morbidity, but no cure has been established. Mesenchymal stem cells (MSCs) critically contribute to bone homeostasis and possess potent immunomodulatory/anti-inflammatory capability. Here, we investigated the therapeutic efficacy of using an infusion of MSCs to treat sex hormone-deficient bone loss and its underlying mechanisms. In particular, we compared the impacts of MSC cytotherapy in the two genders with the aim of examining potential gender differences. Using the gonadectomy (GNX) model, we confirmed that the osteoporotic phenotypes were substantially consistent between female and male mice. Importantly, systemic MSC transplantation (MSCT) not only rescued trabecular bone loss in GNX mice but also restored cortical bone mass and bone quality. Unexpectedly, no differences were detected between the genders. Furthermore, MSCT demonstrated an equal efficiency in rectifying the bone remodeling balance in both genders of GNX animals, as proven by the comparable recovery of bone formation and parallel normalization of bone resorption. Mechanistically, using green fluorescent protein (GFP)-based cell-tracing, we demonstrated rapid engraftment but poor inhabitation of donor MSCs in the GNX recipient bone marrow of each gender. Alternatively, MSCT uniformly reduced the CD3+T-cell population and suppressed the serum levels of inflammatory cytokines in reversing female and male GNX osteoporosis, which was attributed to the ability of the MSC to induce T-cell apoptosis. Immunosuppression in the microenvironment eventually led to functional recovery of endogenous MSCs, which resulted in restored osteogenesis and normalized behavior to modulate osteoclastogenesis. Collectively, these data revealed recipient sexually monomorphic responses to MSC therapy in gonadal steroid deficiency-induced osteoporosis via immunosuppression/anti-inflammation and resident stem cell recovery.

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Increasing the Efficacy of Stem Cell Therapy via Triple-Function Inorganic Nanoparticles.

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