Alveolar Bone Marrow Gli1+ Stem Cells Support Implant Osseointegration

2021 ◽  
pp. 002203452110137
Author(s):  
Y. Yi ◽  
W. Stenberg ◽  
W. Luo ◽  
J.Q. Feng ◽  
H. Zhao
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Dental Implant ◽  
Alveolar Bone ◽  
Lineage Tracing ◽  
Differentiation Markers ◽  
3 Dimensional ◽  
Lineage Differentiation ◽  
Canonical Wnt

Osseointegration is the key issue for implant success. The in vivo properties of cell populations driving the osseointegration process have remained largely unknown. In the current study, using tissue clearing–based 3-dimensional imaging and transgenic mouse model-based lineage tracing methods, we identified Gli1+ cells within alveolar bone marrow and their progeny as the cell population participating in extraction socket healing and implant osseointegration. These Gli1+ cells are surrounding blood vessels and do not express lineage differentiation markers. After tooth extraction and delayed placement of a dental implant, Gli1+ cells were activated into proliferation, and their descendants contributed significantly to new bone formation. Ablation of Gli1+ cells severely compromised the healing and osseointegration processes. Blockage of canonical Wnt signaling resulted in impaired recruitment of Gli1+ cells and compromised bone healing surrounding implants. Collectively, these findings demonstrate that Gli1+ cells surrounding alveolar bone marrow vasculature are stem cells supporting dental implant osseointegration. Canonical Wnt signal plays critical roles in regulating Gli1+ stem cells.

Class I and II Histone Deacetylase Inhibitor LBH589 Promotes Endocrine Differentiation in Bone Marrow Derived Human Mesenchymal Stem Cells and Suppresses Uncontrolled Proliferation

2020 ◽  
Author(s):  
Christoph Schröder ◽  
Rahul Khatri ◽  
Sebastian Friedrich Petry ◽  
Thomas Linn
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Class I ◽  
Differentiation Markers ◽  
Histone Deacetylase Inhibition ◽  
Endocrine Differentiation

AbstractMesenchymal stem cells are useful tools employed in clinical and preclinical medicine. Their beneficial potential in especially degenerative as well as autoimmune diseases is a constant focus of research. Regarding diabetes mellitus, transplantation of stem cells is seen as a possible therapeutic approach to overcome the loss of endocrine pancreatic cells. It was reported that co-transplantation of mesenchymal stem cells with pancreatic islet cells improves function and survival of the graft. However, these multipotent progenitors may be able to form tumors, especially under immunosuppressed conditions. Histone deacetylase inhibitors might offer the potential to overcome this issue. These small molecules can induce cell differentiation and control proliferation. Their potential to control lineage development of stem cells has been distinctly demonstrated in the treatment of cancer, mainly in hematopoietic neoplasias.In this study, we demonstrate that human bone marrow-derived mesenchymal stem cells exhibit low carcinogenic potential in an immunosuppressed condition in vivo. Further, the effect of histone deacetylase inhibitors LBH589, MS-275, and MGCD0103 was examined after normalizing histone deacetylase activities in culture. Interestingly, transcripts of insulin gene enhancer protein and paired-box-gene 6, two markers of pancreatic endocrine differentiation were constitutively expressed in the cell line. The broad spectrum inhibitor of class I and class II histone deacetylases LBH589 upregulated the expression of these transcription factors in a significant way, whereas addition of selective class I histone deacetylase inhibitors MS-275 and MGCD0103 did not result in significant changes in gene expression.In conclusion, we deliver evidence that a combined class I and II histone deacetylase inhibition is able to modulate the transcripts of differentiation markers of mesenchymal stem cells. The treatment holds the capability to facilitate endocrine differentiation in future approaches to replace endocrine cells by stem cell therapy.

scholarly journals The Effect of Smoking Behavior on Alveolar Bone Marrow Mesenchymal Stem Cells of Clinical Implant Patient

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Xicong Zhao ◽  
Bin Zhu ◽  
Yan Duan ◽  
Xin. Wang ◽  
Dehua Li
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Healing ◽  
Direct Evidence ◽  
Alveolar Bone ◽  
Smoking Behavior ◽  
Implant Surgery ◽  
Marrow Mesenchymal Stem Cells

Objective. The hazardous effects of smoking on the alveolar bone healing after implant surgery and nicotine on the biofunction of human alveolar bone marrow mesenchymal stem cells (hABMMSCs) were reported. There was little direct evidence regarding the specific detrimental effects of the smoking on hABMMSCs. The aim of this study was to test the influence of smoking behavior on hABMMSCs and the osseointegration situation after implant surgery. Methods. hABMMSCs from 6 dental implant patients randomly (3 smokers and 3 nonsmokers) were compared. The cell viability, colony forming unit, and cell cycle were performed to assay proliferation capacity. The Oil Red O staining, Alizarin Red staining, alkaline phosphatase staining and activity, adipogenic and osteogenic gene expressions in vitro, and bone formation ectopically in vivo were performed under proper inductions, respectively, to assay multilineage differentiation. Besides the implant stability quotient and marginal bone loss were checked in both groups. Results. Smoking hABMMSCs showed lower proliferation in vitro and poorer bone regeneration capacity in vivo. Moreover, smokers performed worse on bone healing after implant surgery. Conclusions. Our results suggested smoking had the detrimental genetic effect on proliferation and osteogenesis of hABMMSCs and the decreased biofunction of hABMMSCs was positively related with bone healing. Clinical Significance. The present study provided direct evidence about hazardous effects of smoking behavior on hABMMSCs. Smoking decreased the osteogenesis and proliferation of hABMMSCs in vivo and in vitro, and smoking was positively related with osseointegration reduction. Prevention of smoking behavior may promote biofunction of hABMMSCs and successful rate of dental implant.

scholarly journals Efficiency of Cell Therapy to GC-Induced ONFH: BMSCs with Dkk-1 Interference Is Not Superior to Unmodified BMSCs

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Zhun ◽  
Li Donghai ◽  
Yang Zhouyuan ◽  
Zhao Haiyan ◽  
Kang Pengde
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Therapy ◽  
Wnt Pathway ◽  
Allograft Bone ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt ◽  
Dickkopf 1

Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a hip disorder, and it threatens patients who require megadose of steroid therapies. Nowadays, no valid therapies can reverse the development of GC-induced ONFH once it occurs. Stem cell therapy to GC-induced ONFH would be a promising choice. Although the pathogenesis of GC-induced ONFH is not yet fully clear, Dickkopf-1 (Dkk-1) upregulated by excessive GC use, which hinders the canonical Wnt pathway, could be an explanation. Thus, the aim of the present work lies in investigating the efficiency of the allograft bone marrow stem cells (BMSCs) with Dkk-1 interference in preventing the progression of the GC-induced ONFH. Lentivirus-meditated Dkk-1 RNAi was introduced into BMSCs which was exposed to dexamethasone (10−6 mol/L) in vitro. This interference blocked Dkk-1 overexpression by GC and afterwards prompted the transduction of Wnt/β-catenin in which the Runx2 and PPARγ were upregulated and downregulated, respectively. Thus, the osteogenesis was promoted while adipogenesis was inhibited. In vivo, GC-induced ONFH rats were treated by allotransplantation of BMSCs with Dkk-1 interference, and the progression of the disease was prevented. However, the effects were not significantly superior to treatment with nongenetically modified or normal BMSCs.

In vivo alveolar bone regeneration by bone marrow stem cells/fibrin glue composition

2012 ◽  
Vol 57 (3) ◽  
pp. 238-244 ◽  
Author(s):  
Liang Zhang ◽  
Peihuan Wang ◽  
Shenglin Mei ◽  
Chenghua Li ◽  
Chuan Cai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Regeneration ◽  
Fibrin Glue ◽  
Alveolar Bone ◽  
Bone Marrow Stem Cells

Bone Marrow Mesenchymal Stem Cells Derived Discoidin Domain-Containing Receptor 2 (DDR2) as a Communication Mediator to Strengthen the Invasiveness and Metastasis of Papillary Thyroid Carcinoma

2022 ◽  
Vol 12 (3) ◽  
pp. 514-522
Author(s):  
Xiongsheng Xiao ◽  
Zhi Zhang ◽  
Hongpo Xie ◽  
Siyi Li ◽  
Jianwen Li
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Distant Metastasis ◽  
Abdominal Cavity ◽  
Malignant Cells ◽  
Lineage Differentiation ◽  
Marrow Mesenchymal Stem Cells ◽  
Metastatic Sites

Our current study plans to dissect the impacts and its underlying mechanisms of bone marrow mesenchymal stem cells (BMSCs) on the invasive and metastatic features of PTC. Clinical specimens from distantly metastatic PTC were collected to measure DRR2 level. After being identified via tri-lineage differentiation and flow cytometry, BMSCs were co-cultured with PTC cells followed by analysis of cell proliferation and migration by CCK-8 and Transwell assays, expression of DDR2 and EMT-associated proteins by Western blot. Eventually, shDDR2-transfected BMSCs were infused with PTC cells into the abdominal cavity of mice to establish a mouse model assess their effect on tumor growth and distant metastasis. DDR2 was upregulated in BMSCs and malignant cells located in the metastatic sites. Co-culture with BMSCs enhanced DRR2 expression in PTC cells, which was simultaneously accompanied by the escalated mesenchymalization process. In vivo experiments exhibited that co-injection with BMSCs facilitated disease progression and distant metastasis of malignancies. Instead, DDR2 knockdown significantly impeded BMSCs-triggered migrative and proliferative behaviors of malignant cells. In conclusion, DDR2 derived from BMSCs can function as a communication mediator to strengthen the invasiveness and metastasis of PTC.

Evaluation of Mesenchymal Stem Cell Angiogenic Capacity Driven by Wnt3a for Enhanced Wound Healing

2019 ◽  
Vol 9 (8) ◽  
pp. 1027-1037
Author(s):  
Kai Yi ◽  
Yanting Liu ◽  
Xiangwei Zhang ◽  
Hongbin Zhou
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Cutaneous Wound ◽  
Angiogenesis Process ◽  
Novel Method ◽  
Canonical Wnt ◽  
Related Process

It has been acknowledged that the inferior viability of exogenous bone marrow-derived mesenchymal stem cells (BMSCs) may impede the clinical application of them for tissue engineering such as wound healing, in addition, how to enhance the angiogenic capacity of BMSCs for wound regeneration still remains a major challenge for surgeons. Wnt3a, a member of the classic canonical Wnt/β-signaling pathway, has been demonstrated to be able to regulate the balance of macrophage to make them acquire a pro-angiogenic phenotype, thus increasing the formation of new endothelial cells (ECs) for the further vascularization of wound. In this study we investigated a novel method by using the engraftment of exogenous BMSCs combined with Wnt3a to evaluate whether the strategy may enhance the viability of the stem cells and further promote wound healing. The in vitro culture of BMSCs with the presence of Wnt3a accompanied with the murine model with cutaneous wound treated with BMSC + Wnt3a were evaluated. The angiogenesis related markers including VEGF, NG2, α-SMA, CD31 were utilized to investigate whether the angiogenic capacity of BMSCs was promoted by Wnt3a. After 7 days culture with Wnt3a, stem cells showed direct differentiation into the vital cells that were required in angiogenesis related process. For in vivo test, murine wounds intervened by BMSCs coupled with Wnt3a showed enhanced vascularization featured as formation of blood vessels than did single BMSC engraftment or Wnt3a alone. More importantly, the representative markers of angiogenesis process (VEGF, NG2, α-SMA, CD31) were up-regulated in the animals managed with BMSCs coupled with Wnt3a. Overall, our results indicated that the combinatory therapy by using Wnt3a and BMSCs is capable of accelerating the wound healing via stimulating the angiogenic capacity of stem cells, thus enhancing the angiogenesis process within the wound.

scholarly journals In Vivo Study for Clinical Application of Dental Stem Cell Therapy Incorporated with Dental Titanium Implants

Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 381
Author(s):  
Hyunmin Choi ◽  
Kyu-Hyung Park ◽  
Narae Jung ◽  
June-Sung Shim ◽  
Hong-Seok Moon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Formation ◽  
Alveolar Bone ◽  
Human Mesenchymal Stem Cells ◽  
Titanium Implants ◽  
Osteogenic Potential ◽  
Induction Medium ◽  
Radiographic Analysis ◽  
New Bone Formation

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

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