A specific affinity cyclic peptide enhances the adhesion, expansion and proliferation of rat bone mesenchymal stem cells on β‑tricalcium phosphate scaffolds

Sun, Tiantong; Man, Zhentao; Peng, Changliang; Wang, Guozong

doi:10.3892/mmr.2019.10335

Cited by 8 publications

(11 citation statements)

References 51 publications

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“…Western blotting showed that B7-H3 OE exosomes were able to increase endogenous B7-H3 levels in HMECs by 467% ( p < 0.001) ( Figure 3 C) suggesting B7-H3 may influence the tumor microenvironment through exosomes. UW228 cells, with lower Myc [ 42 ] and B7-H3 levels ( Supplementary Figure S1B ) when incubated with D283 exosomes showed increased B7-H3 while showing a 48% decrease ( p < 0.001) in p-STAT1 levels ( Figure 3 D). These results suggest a receptor-independent role of B7-H3 that may indicate distal and proximal roles of B7-H3 in the cancer microenvironment.…”

Section: Resultsmentioning

confidence: 99%

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role

Purvis

Velpula

Guda

et al. 2020

IJMS

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(1) Aim: Medulloblastoma is the most common aggressive pediatric cancer of the central nervous system. Improved therapies are necessary to improve life outcomes for medulloblastoma patients. Exosomes are a subset of extracellular vesicles that are excreted outside of the cell, and can transport nucleic acids and proteins from donor cells to nearby recipient cells of the same or dissimilar tissues. Few publications exist exploring the role that exosomes play in medulloblastoma pathogenesis. In this study, we found B7-H3, an immunosuppressive immune checkpoint, present in D283 cell-derived exosomes. (2) Methods: Utilizing mass spectrometry and immunoblotting, the presence of B7-H3 in D283 control and B7-H3 overexpressing exosomes was confirmed. Exosomes were isolated by Systems Biosciences from cultured cells as well as with an isolation kit that included ultracentrifugation steps. Overlay experiments were performed to determine mechanistic impact of exosomes on recipient cells by incubating isolated exosomes in serum-free media with target cells. Impact of D283 exosome incubation on endothelial and UW228 medulloblastoma cells was assessed by immunoblotting. Immunocytochemistry was employed to visualize exosome fusion with recipient cells. (3) Results: Overexpressing B7-H3 in D283 cells increases exosomal production and size distribution. Mass spectrometry revealed a host of novel, pathogenic molecules associated with B7-H3 in these exosomes including STAT3, CCL5, MMP9, and PI3K pathway molecules. Additionally, endothelial and UW228 cells incubated with D283-derived B7-H3-overexpressing exosomes induced B7-H3 expression while pSTAT1 levels decreased in UW228 cells. (4) Conclusions: In total, our results reveal a novel role in exosome production and packaging for B7-H3 that may contribute to medulloblastoma progression.

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Section: Resultsmentioning

confidence: 99%

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role

Purvis

Velpula

Guda

et al. 2020

IJMS

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“…Our previous study demonstrated that the specific affinity cyclic peptide D7 could enhance the adhesion, expansion, and proliferation of BMSCs on β -tricalcium phosphate scaffolds [ 31 ]; therefore, we tested the potential therapeutic effects of D7 on DEX-induced BMSCs damage. To our surprise, D7 exhibited a powerful rescue effect against DEX-induced BMSCs damage, as demonstrated by concentration-dependent amelioration of BMSCs proliferation in CCK-8 assays ( Figure 3(a) ) and reduced expression of apoptosis markers, including LDH activity, cleaved-PARP levels, and cleaved-caspase 3 levels (Figures 3(b) – 3(d) ).…”

Section: Resultsmentioning

confidence: 99%

“…In our previous study, we had screened cyclic polypeptide D7 from the cyclic peptide phage display library (Ph.D.-C7C) by phage display technology [ 31 ]. Phage display is a robust, high-throughput screening strategy in which a library of peptide or protein variants is expressed on the outside of a phage virion, and the genetic material encoding each variant is present on the inside of the virion [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…Based on the different binding affinities of the cyclic peptide and the target cell, we screened D7 through three or four biopanning procedures, following previously described protocols [ 33 , 34 ]. In addition, we demonstrated that D7 could enhance the adhesion, expansion, and proliferation of BMSCs on β -tricalcium phosphate scaffolds [ 31 ], in contrast to the pathophysiological changes related to SONFH.…”

Section: Introductionmentioning

confidence: 99%

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Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15-Mediated Redox Signaling

Chen

Cui

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Osteonecrosis of the femoral head (ONFH) is a debilitating disease that is closely associated with the clinical application of high-dose glucocorticoids. Elevated oxidative stress contributes to the pathophysiological changes observed in ONFH. The lack of effective treatments besides surgical intervention highlights the importance of finding novel therapeutics. Our previous studies demonstrated that D7, a cyclic polypeptide, enhances the adhesion, expansion, and proliferation of bone marrow mesenchymal stem cells (BMSCs). Therefore, in this study, we investigated the therapeutic effects of D7 against ONFH in BMSCs and evaluated the underlying mechanisms. First, we screened for ONFH risk factors. Then, we applied D7 treatment to steroid-induced ONFH (SONFH) in an in vitro model produced by dexamethasone (DEX) to further elucidate the underlying mechanisms. We found negative correlations among oxidative stress marker expression, growth differentiation factor 15 (GDF15) levels, and ONFH. Furthermore, we demonstrated that DEX inhibited the proliferation and induced apoptosis of BMSCs by suppressing GDF15/AKT/mammalian target of rapamycin (mTOR) signaling. D7 alleviated DEX-induced BMSCs injury and restored the chondrogenic function of BMSCs by activating GDF15/AKT/mTOR signaling. In addition, DEX-induced excessive reactive oxygen species (ROS) generation was an upstream trigger of GDF15-mediated signaling, and D7 ameliorated this DEX-induced redox imbalance by restoring the expression of antioxidants, including superoxide dismutase (SOD) 1, SOD2, and catalase, via regulation of GDF15 expression. In conclusion, our findings revealed the potential therapeutic effects of D7 in SONFH and showed that this protective function may be mediated via inhibition of DEX-induced ROS and activation of GDF15/AKT/mTOR signaling, thereby providing insights into the potential applications of D7 in SONFH treatment.

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“…They found good proliferation and expansion of the stem cells, with potential for use in in vivo bone tissue engineering. Additionally, they saw an increase in activity of the BMSCs with their scaffold [ 68 ]. Another study used carboxymethyl chitosan/alginate 3D scaffold with BMSCs in an osteonecrosis of femoral head (ONFH) rabbit model over 12 weeks.…”

Section: Desired Characteristics Of 3d Scaffoldsmentioning

confidence: 99%

Tissue Engineering Strategies for Treating Avascular Necrosis of the Femoral Head

et al. 2021

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Avascular necrosis (AVN) of the femoral head commonly leads to symptomatic osteoarthritis of the hip. In older patients, hip replacement is a viable option that restores the hip biomechanics and improves pain but in pediatric, adolescent, and young adult patients hip replacements impose significant activity limitations and the need for multiple revision surgeries with increasing risk of complication. Early detection of AVN requires a high level of suspicion as diagnostic techniques such as X-rays are not sensitive in the early stages of the disease. There are multiple etiologies that can lead to this disease. In the pediatric and adolescent population, trauma is a commonly recognized cause of AVN. The understanding of the pathophysiology of the disease is limited, adding to the challenge of devising a clinically effective treatment strategy. Surgical techniques to prevent progression of the disease and avoid total hip replacement include core decompression, vascular grafts, and use of bone-marrow derived stem cells with or without adjuncts, such as bisphosphonates and bone morphogenetic protein (BMP), all of which are partially effective only in the very early stages of the disease. Further, these strategies often only improve pain and range of motion in the short-term in some patients and do not predictably prevent progression of the disease. Tissue engineering strategies with the combined use of biomaterials, stem cells and growth factors offer a potential strategy to avoid metallic implants and surgery. Structural, bioactive biomaterial platforms could help in stabilizing the femoral head while inducing osteogenic differentiation to regenerate bone and provide angiogenic cues to concomitantly recover vasculature in the femoral head. Moreover, injectable systems that can be delivered using a minimal invasive procedure and provide mechanical support the collapsing femoral head could potentially alleviate the need for surgical interventions in the future. The present review describes the limitations of existing surgical methods and the recent advances in tissue engineering that are leading in the direction of a clinically effective, translational solution for AVN in future.

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A specific affinity cyclic peptide enhances the adhesion, expansion and proliferation of rat bone mesenchymal stem cells on β‑tricalcium phosphate scaffolds

Cited by 8 publications

References 51 publications

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role

Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15-Mediated Redox Signaling

Tissue Engineering Strategies for Treating Avascular Necrosis of the Femoral Head

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