Injection of synthetic mesenchymal stem cell mitigates osteoporosis in rats after ovariectomy

Abstract

Osteoporosis is a severe skeletal disorder. Patients have a low bone mineral density and bone structural deterioration. Mounting lines of evidence suggest that inappropriate apoptosis of osteoblasts/osteocytes leads to maladaptive bone remodelling in osteoporosis. It has been suggested that transplantation of stem cells, including mesenchymal stem cells, may alter the trajectory of bone remoulding and mitigate osteoporosis in animal models. However, stem cells needed to be carefully stored and characterized before usage. In addition, there is great batch‐to‐batch variation in stem cell production. Here, we fabricated therapeutic polymer microparticles from the secretome and membranes of mesenchymal stem cells (MSCs). These synthetic MSCs contain growth factors secreted by MSCs. In addition, these particles display MSC surface molecules. In vitro, co‐culture with synthetic MSCs increases the viability of osteoblast cells. In a rat model of ovariectomy‐induced osteoporosis, injection of synthetic MSCs mitigated osteoporosis by reducing cell apoptosis and systemic inflammation, but increasing osteoblast numbers. Synthetic MSC offers a promising therapy to manage osteoporosis.

Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis

“…Li et al 156 and Chen et al 157 explored the effects of EVs on the osteogenic, proliferation, and migration capabilities of BMMSCs in vitro, and demonstrated that EVs derived from ASCs promoted bone regeneration. Shen et al 158 found that EVs fabricated from BMMSCs contained growth factors secreted by MSCs, and co‐culture with EVs in vitro increased the viability of osteoblast cells. Further in vivo experiments confirmed that injection of EVs mitigated OVX‐induced osteoporosis by reducing cell apoptosis and systemic inflammation, but increasing osteoblast numbers.…”

Nanoparticles functionalized with stem cell secretome and CXCR4-overexpressing endothelial membrane for targeted osteoporosis therapy

“…Stem cells release cytokines, chemokines, growth factors, and different types of extracellular vesicles (EVs) as part of their paracrine signaling system. To mimic the biofunction of stem cells, we and other groups have developed synthetic stem cells by loading conditioned medium to coat the cell membrane for injured heart or liver regeneration [ 21 – 25 ]. We have confirmed the synthetic stem cells’ superior stability even after repeated freeze–thaw cycles while maintaining high therapeutic efficiency.…”

Mitigation of Sodium Iodate-Induced Cytotoxicity in Retinal Pigment Epithelial Cells in vitro by Transgenic Erythropoietin-Expressing Mesenchymal Stem Cells

“…In order to prevent further loss of RPE cells, MSCs can be used as a cell source for treatment (Cislo-Pakuluk and Marycz, 2017). Recently, the production of synthetic MSCs through the packaging of MSC-secreted factors into carriers have shown high promise in animal models of osteoporosis (Shen et al, 2018) and acute myocardial infarction (Lee et al, 2017). This method replaces the direct use of MSC in treatment with the secretome, and thus, circumventing certain drawbacks such as reduced transplant survivability (English and Wood, 2013), undesired differentiation (Volarevic et al, 2018), and tumor promotion (Volarevic et al, 2018).…”