Abstract
ABSTRACTRecently, several studies have demonstrated that intravenous administration of mesenchymal stem cells (MSCs) improve medication‐related osteonecrosis of the jaw (MRONJ), and paracrine effects of secretomes from MSCs have been hypothesized as the primary contributors. These secretomes in conditioned media from human MSCs (MSC‐CM) were previously demonstrated to promote bone and tissue regeneration. Because MSC‐CM contain cytokines monocyte chemoattractant protein (MCP)‐1, insulin growth factor (IGF)‐1, and vascular endothelial growth factor (VEGF) at relatively higher concentrations than other factors, these cytokines were considered as relevant active factors for tissue regeneration. By mixing the recombinant proteins of MCP‐1, IGF‐1, and VEGF, included at the same concentrations in MSC‐CM, we prepared cytokine mixtures mimicking MSC‐CM and then evaluated its therapeutic effects in a rat MRONJ model. In vitro, cytokine mixtures promoted osteogenic differentiation, migration, and proliferation of rat MSCs. In addition, these maintained osteoclastic function. In vivo, we used a rat MRONJ model to examine therapeutic effects of the cytokine mixtures through intravenous administration. In MSC‐CM or cytokine mixture group, open alveolar sockets in 66% or 67% of the rats with MRONJ, respectively, healed with complete soft tissue coverage and socket bones, whereas in the other groups, the exposed necrotic bone with inflamed soft tissue remained. Histological analysis revealed new bone formation and the appearance of osteoclasts in MSC‐CM or cytokine mixture group; however, osteoclasts were significantly reduced in the other groups. Thus, we concluded that intravenous administration of cytokine mixtures might be an effective therapeutic modality for treating patients with MRONJ. © 2017 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research
Highlights
Bisphosphonates (BPs) were originally developed as drugs for the treatment of bone-resorbing diseases such as multiple myeloma and bone metastasis, whose typical origins are breast and prostate cancers as well as tumor-related hypercalcemia,(1–4) and for preventing pathological fractures in patients with osteoporosis
We previously reported therapeutic effects of mesenchymal stem cells (MSCs)-conditioned media (CM) in a rat medicationrelated osteonecrosis of the jaw (MRONJ) model.[19] we reported that MSC-CM contains numerous cytokines, including monocyte chemoattractant protein (MCP)-1, insulin growth factor (IGF)-1, and vascular endothelial growth factor (VEGF).(19,20) These cytokines regulate migration, angiogenesis, antiapoptosis, and osteogenesis in host MSCs, osteoclast precursors, or immune cells in inflamed tissues and may accelerate the regeneration of bone and other tissues.[21,22]
The viability of Rat MSCs (rMSCs) and rat osteoclasts (rOCs) was decreased with only Zol, single cytokine, two combination cytokines, or MSC-CM-dep MIV
Summary
Bisphosphonates (BPs) were originally developed as drugs for the treatment of bone-resorbing diseases such as multiple myeloma and bone metastasis, whose typical origins are breast and prostate cancers as well as tumor-related hypercalcemia,(1–4) and for preventing pathological fractures in patients with osteoporosis. Several issues with stem cells remain to be addressed, including tumorigenesis,(15) poor survival of implanted cells,(16) and transmission of infectious diseases. Because implanted MSCs may contribute to tissue regeneration via pluripotency and via paracrine effects,(17,18) secretomes in conditioned media from human MSCs (MSC-CM), which are known to include various types of cytokines and other factors, may help address these issues. We previously reported therapeutic effects of MSC-CM in a rat MRONJ model.[19] we reported that MSC-CM contains numerous cytokines, including monocyte chemoattractant protein (MCP)-1, insulin growth factor (IGF)-1, and vascular endothelial growth factor (VEGF).(19,20) These cytokines regulate migration, angiogenesis, antiapoptosis, and osteogenesis in host MSCs, osteoclast precursors, or immune cells in inflamed tissues and may accelerate the regeneration of bone and other tissues.[21,22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
