Protective effects of conditioned media of immortalized stem cells from human exfoliated deciduous teeth on pressure ulcer formation

Abstract

Pressure ulcers (PUs) are increasing with aging worldwide, but there is no effective causal therapy. Although mesenchymal stem cells (MSCs) promote cutaneous wound healing, the effects of the conditioned medium (CM) of MSCs on cutaneous PU formation induced by ischemia-reperfusion injury have been poorly investigated. To address this issue, herein, we first established an immortalized stem cell line from human exfoliated deciduous teeth (SHED). This cell line was revealed to have superior characteristics in that it grows infinitely and vigorously, and stably and consistently secretes a variety of cytokines. Using the CM obtained from the immortalized SHED cell line, we investigated the therapeutic potential on a cutaneous ischemia-reperfusion mouse model for PU formation using two magnetic plates. This is the first study to show that CM from immortalized SHEDs exerts therapeutic effects on PU formation by promoting angiogenesis and oxidative stress resistance through vascular endothelial growth factor and hepatocyte growth factor. Thus, the CM of MSCs has potent therapeutic effects, whereas these therapies have not been implemented in human medicine. To try to meet the regulatory requirements for manufacturing and quality control as much as possible, it is necessary to produce CM that is consistently safe and effective. The immortalization of stem cells could be one of the breakthroughs to meet the regulatory requirements and consequently open up a novel avenue to create a novel type of cell-free regenerative medicine, although further investigation into the quality control is warranted.

From Teeth to Therapy: A Review of Therapeutic Potential within the Secretome of Stem Cells from Human Exfoliated Deciduous Teeth

“…The in vivo study by Hiraki et al (2020) also proposed cytokines and growth factors in SHED-derived secretome, particularly M-CSF, ANG, VEGF-A, MCP-1, VEGF-C, and bFGF, to be the main actors in the angiogenesis in the calvarial bone defect model of a mouse [64]. Additionally, VEGF, together with HGF, were also found to play roles in angiogenesis stimulation in the pressure ulcer mouse model [76].…”

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients

“…Indeed, numerous studies have shown that autologous transplantation of SHEDs, for example, may be a safe and promising approach for both dentin and pulp regeneration (reviewed in [ 28 ]), but their applications far exceed the orthodontic field, as SHEDs have also been tested for their regenerative potential against spinal cord injury [ 29 , 30 , 31 ], hypoxic–ischemic brain injury [ 32 ], ovariectomy-induced osteoporosis [ 33 ], liver fibrosis [ 34 ], and systemic lupus erythematosus [ 35 ]. And that potential lies not only in the cells themselves but also in the conditioned media one may collect from their culture, as elegantly shown by Katahira and co-workers in a recent study, where they immortalized a SHED cell line and analyzed the effects of its conditioned medium on cutaneous pressure ulcers [ 36 ].…”

Modelling Lysosomal Storage Disorders in an innovative way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidoses Type II Patients

“…But their applications far exceed the orthodontic field, as SHEDs have also been tested for their regenerative potential against spinal cord injury [ [29][30][31], hypoxic-ischemic brain injury [32], ovariectomy-induced osteoporosis [33], liver fibrosis [34], and systemic lupus erythematosus [35]. And that potential lies not only on the cells themselves but also in the conditioned media one may collect from their culture, as elegantly shown by Murakami and co-workers in a recent study, where the authors immortalized a SHED cell line, and analysed the effects of its conditioned medium on cutaneous pressure ulcers [36].…”