Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem/Progenitor Cells

Hazehara-Kunitomo, Yuri; Hara, Emilio Satoshi; Ono, M.; Aung, Kyaw Thu; Komi, Keiko; Pham, Hai Thanh; Akiyama, Kentaro; Okada, Masahiro; Oohashi, Toshitaka; Matsumoto, Takuya; Kuboki, Takuo

doi:10.3390/ijms20051097

Cited by 33 publications

(15 citation statements)

References 17 publications

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“…It has been reported that calcium ions stabilize or enhance the viability of dental pulp cells [ 44 ], periodontal ligament cells [ 45 ], and odontoblasts [ 46 ]. Additionally, pH is also an important factor that influences the wound healing process by changing throughout the process [ 47 , 48 , 49 ]. In our previous study, we revealed that periodontal ligament cells, and osteoblast-like cells cultured with the prototype of CS-BG within the pH range of 9 to 10 had no adverse effects [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Physicochemical Properties, Cytocompatibility, and Biocompatibility of a Bioactive Glass Based Retrograde Filling Material

et al. 2021

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The ideal retrograde filling material that is easy to handle, has good physicochemical properties, and is biocompatible has not yet been developed. The current study reports the development of a novel bioactive glass based powder for use as a retrograde filling material that is capable of altering the consistency and hardening rate of mixtures when mixed with existing bioactive glass based cement. Furthermore, its physicochemical properties, in vitro effects on human cementoblast-like cells, and in vivo effects on inflammatory responses were evaluated. The surface of the hardened cement showed the formation of hydroxyapatite-like precipitates and calcium and silicate ions were eluted from the cement when the pH level was stabilized at 10.5. Additionally, the cement was found to be insoluble and exhibited favorable handling properties. No adverse effects on viability, proliferation, and expression of differentiated markers were observed in the in vitro experiment, and the cement was capable of inducing calcium deposition in the cells. Moreover, the cement demonstrated a lower number of infiltrated inflammatory cells compared to the other materials used in the in vivo mouse subcutaneous implantation experiment. These findings suggest that the retrograde filling material composed of bioactive glass and the novel bioactive glass based powder exhibits favorable physicochemical properties, cytocompatibility, and biocompatibility.

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Section: Discussionmentioning

confidence: 99%

Physicochemical Properties, Cytocompatibility, and Biocompatibility of a Bioactive Glass Based Retrograde Filling Material

et al. 2021

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“…osteosarcoma [52], and the maintenance of stemness in mesenchymal cells [53,54]. Also, OCT-4 expression in murine fibroblasts increases as pH shifts from 7.4 to 6.5 [55].…”

Section: Discussionmentioning

confidence: 99%

The acidic tumor microenvironment drives a stem-like phenotype in melanoma cells

et al. 2020

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Acidosis characterizes the microenvironment of most solid tumors and is considered a new hallmark of cancer. It is mainly caused by both “aerobic” and “anaerobic” glycolysis of differently adapted cancer cells, with the final product lactic acid being responsible of the extracellular acidification. Many evidences underline the role of extracellular acidosis in tumor progression. Among the different findings, we demonstrated that acidosis-exposed cancer cells are characterized by an epithelial-to-mesenchymal transition phenotype with high invasive ability, high resistance to apoptosis, anchorage-independent growth, and drug therapy. Acidic melanoma cells over-express SOX2, which is crucial for the maintenance of their oxidative metabolism, and carbonic anhydrase IX, that correlates with poor prognosis of cancer patients. Considering these evidences, we realized that the profile outlined for acid cancer cells inevitably remind us the stemness profile. Therefore, we wondered whether extracellular acidosis might induce in cancer cells the acquisition of stem-like properties and contribute to the expansion of the cancer stem cell sub-population. We found that a chronic adaptation to acidosis stimulates in cancer cells the expression of stem-related markers, also providing a high in vitro/in vivo clonogenic and trans-differentiating ability. Moreover, we observed that the acidosis-induced stem-like phenotype of melanoma cells was reversible and related to the EMT induction. These findings help to characterize a further aspect of stem cell niche, contributing to the sustainment and expansion of cancer stem cell subpopulation. Thus, the usage of agents controlling tumor extracellular acidosis might acquire great importance in the clinic for the treatment of aggressive solid tumor. Key messages • Extracellular acidosis up-regulates EMT and stem-related markers in melanoma cells • Acidic medium up-regulates in vitro self-renewal capacity of melanoma cells • Chronic acidosis adaptation induces trans-differentiation ability in melanoma cells • Melanoma cells adapted to acidosis show higher tumor-initiating potential than control cells • Extracellular acidosis promotes a stem-like phenotype in prostate and colorectal carcinoma cells

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“…This SMH/GO-promoted BMSCs migration and osteogenic differentiation was tightly associated with the degradation products of hydrogels. Normally, BMSCs are recruited to wound sites by chemokines and pro-inflammatory cytokines at the early stage of bone healing 49. The recruited BMSCs mineralize (mineralized nodules formation is a typical marker for BMSCs osteogenic differentiation) and differentiate into osteoblasts in the presence of an array of cytokines, thus promoting bone repair.…”

Section: Discussionmentioning

confidence: 99%

A sericin/ graphene oxide composite scaffold as a biomimetic extracellular matrix for structural and functional repair of calvarial bone

Deng

et al. 2020

Theranostics

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Bone defects affect millions of people worldwide each year, leading to severe disabilities. Biomimetic scaffolds mediated tissue regeneration represents a promising alternative for bone repair. However, the major problem associated with most currently clinical available artificial bone substitutes (scaffolds) is that they mainly possess filling function but lack of osteo-induction abilities. Therefore, development of biomaterials with osteo-induction property for effective bone regeneration is highly desired.Methods: We report the design and fabrication of a photo-crosslinked sericin methacryloyl (SerMA)/ graphene oxide (GO) hydrogel (SMH/GO) as a biomimetic scaffold for the functional repair of the bone. The mechanical strength, degradation and biocompatibility behavior of SMH/GO hydrogel were measured in vitro. The effect of SMH/GO hydrogel on BMSCs proliferation, migration, osteogenesis differentiation was assessed. After that, SMH/GO-2 was used as an artificial bone substitute for bone regeneration after calvarial defects and effect on bone repair was evaluated by histological, X-Ray and microCT analysis. Furthermore, the potential mechanism of SMH/GO hydrogel regulating BMSCs migration and differentiation was investigated by RNA sequencing.Results: This scaffold has good biocompatibility, cell adhesive property, proliferation- and migration-promoting effects, and osteogenic induction property. After being implanted in a rat calvarial defect model, this SMH/GO scaffold effectively promotes new bone regeneration and achieves structural and functional repair within 12 weeks by inducing autologous bone marrow-derived mesenchymal stem cells (BMSCs) differentiation. By utilizing cell-biological assays and RNA sequencing, we reveal its possible regeneration mechanisms: the SMH/GO hydrogel regulates BMSCs migration and osteo-differentiation via activating MAPK, TNF, and chemokine signaling for bone regeneration.Conclusion: Aiming to meet clinical demands and overcome current limitations of existing artificial bones, we have developed a new type of sericin/ graphene oxide composite scaffold and provided histological, functional, and molecular evidence demonstrating that it is capable of effectively repairing defective bones by inducing autologous BMSCs directional migration and osteogenic differentiation.

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Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem/Progenitor Cells

Cited by 33 publications

References 17 publications

Physicochemical Properties, Cytocompatibility, and Biocompatibility of a Bioactive Glass Based Retrograde Filling Material

Physicochemical Properties, Cytocompatibility, and Biocompatibility of a Bioactive Glass Based Retrograde Filling Material

The acidic tumor microenvironment drives a stem-like phenotype in melanoma cells

A sericin/ graphene oxide composite scaffold as a biomimetic extracellular matrix for structural and functional repair of calvarial bone

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