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Stem Cell Research & Therapy Jul 2021Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely dicussed and systemic application was also a feasible way for new bone formation, the aim of this study was to systematically review systemic therapy of MSCs for bone regeneration in pre-clinical studies.
METHODS
The article search was conducted in PubMed and Embase databases. Original research articles that assessed potential effect of systemic application of MSCs for bone regeneration in vivo were selected and evaluated in this review, according to eligibility criteria. The efficacy of MSC systemic treatment was analyzed by random effects meta-analysis, and the outcomes were expressed in standard mean difference (SMD) and its 95% confidence interval. Subgroup analyses were conducted on animal species and gender, MSCs types, frequency and time of injection, and bone diseases.
RESULTS
Twenty-three articles were selected in this review, of which 21 were included in meta-analysis. The results showed that systemic therapy increased bone mineral density (SMD 3.02 [1.84, 4.20]), bone volume to tissue volume ratio (2.10 [1.16, 3.03]), and the percentage of new bone area (7.03 [2.10, 11.96]). Bone loss caused by systemic disease tended to produce a better response to systemic treatment (p=0.05 in BMD, p=0.03 in BV/TV).
CONCLUSION
This study concluded that systemic therapy of MSCs promotes bone regeneration in preclinical experiments. These results provided important information for the systemic application of MSCs as a potential application of bone formation in further animal experiments.
Topics: Animals; Bone Regeneration; Bone and Bones; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteogenesis
PubMed: 34215342
DOI: 10.1186/s13287-021-02456-w -
Bone Reports Dec 2021There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve...
There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis of published studies to investigate the efficacy of stem cell therapy to rescue bone brittleness in mouse models of OI. Identified studies included bone marrow, mesenchymal stem cells, and human fetal stem cells. Effect size of fracture incidence, maximum load, stiffness, cortical thickness, bone volume fraction, and raw engraftment rates were pooled in a random-effects meta-analysis. Cell type, cell number, injection route, mouse age, irradiation, anatomical bone, and follow up time were considered as moderators. It was not possible to investigate further parameters due to the lack of standards of investigation between the studies. Despite the use of mice in the majority of the investigations considered and the lack of sham mice as control, this study demonstrates the promising potential of stem cell therapy to reduce fractures in OI. Although their low engraftment, cell therapy in mouse models of OI had a beneficial effect on maximum load, but not on stiffness, cortical thickness and bone volume. These parameters all depend on bone geometry and do not inform on its material properties. Being bone fractures the primary symptom of OI, there is a critical need to measure the fracture toughness of OI bone treated with stem cells to assess the actual efficacy of the treatment to rescue OI bone brittleness.
PubMed: 34368408
DOI: 10.1016/j.bonr.2021.101108 -
JBMR Plus Jan 2018Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the... (Review)
Review
Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the pathogenesis of AFFs is unknown, their identification in bisphosphonate-naïve individuals and in monogenetic bone disorders has led to the hypothesis that genetic factors predispose to AFF. Our aim was to review and summarize the evidence for genetic factors in individuals with AFF. We conducted structured literature searches and hand-searching of conference abstracts/reference lists for key words relating to AFF and identified 2566 citations. Two individuals independently reviewed citations for (i) cases of AFF in monogenetic bone diseases and (ii) genetic studies in individuals with AFF. AFFs were reported in 23 individuals with the following 7 monogenetic bone disorders (): osteogenesis imperfecta (), pycnodysostosis (), hypophosphatasia (), X-linked osteoporosis (), osteopetrosis, X-linked hypophosphatemia (), and osteoporosis pseudoglioma syndrome (). In 8 cases (35%), the monogenetic bone disorder was uncovered after the AFF occurred. Cases of bisphosphonate-naïve AFF were reported in pycnodysostosis, hypophosphatasia, osteopetrosis, X-linked hypophosphatemia, and osteoporosis pseudoglioma syndrome. A pilot study in 13 AFF patients and 268 controls identified a greater number of rare variants in AFF cases using exon array analysis. A whole-exome sequencing study in 3 sisters with AFFs showed, among 37 shared genetic variants, a p.Asp188Tyr mutation in the gene in the mevalonate pathway, critical to osteoclast function, which is also inhibited by bisphosphonates. Two studies completed targeted gene sequencing, an heterozygous mutation was found in 1 case of a cohort of 11 AFFs, whereas the second study comprising 10 AFF cases did not find mutations in . Targeted sequencing of , , , and genes in 5 cases of AFF identified a variant in COL1A2 in 1 case. These findings suggest a genetic susceptibility for AFFs. A large multicenter collaborative study of well-phenotyped AFF cases and controls is needed to understand the role of genetics in this uncommon condition.
PubMed: 30283886
DOI: 10.1002/jbm4.10024 -
Orthopaedic Surgery Aug 2020To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients with osteogenesis imperfecta (OI).
METHODS
Studies were eligible for inclusion if they were randomized controlled trials of directly comparing oral bisphosphonate therapy with placebo-group in OI patients. Data synthesis regarding to bone mineral density as measured by dual-energy X-ray absorptiometry (DEXA), decreased fracture incidence, change in biochemical markers of bone and mineral metabolism, bone histology, growth, bone pain, quality of life, and others were assessed, and meta-analysis done when possible.
RESULTS
From 98 potential references and six randomized controlled studies a total of 263 participants receiving oral bisphosphonates and 143 placebo treatments contributed data to meta-analysis. Pooled meta-analysis of three studies suggested that there was significant difference between bisphosphonate treated group and placebo in number of patients with at least one fracture (mean difference 0.53, 95% confidence interval 0.32-0.89, P = 0.02). Pooled meta-analysis of two studies suggested that significant difference was noted between bisphosphonate treated group and placebo in mean percentage change in spine BMD (T-score) (mean difference 28.43, 95% confidence interval 7.09-49.77, P = 0.009). The similar effect was shown in the term of mean change (Z-score) in spine BMD.
CONCLUSIONS
Significant improvement in lumbar areal BMD in patients affected with OI has been shown when treated with oral bisphosphonates, even though only a small population was enrolled. We cannot draw a definite conclusion that the increase in BMD can be translated into fracture reduction and clinical functional improvement. The optimal method, dose, type, initiation, and duration of oral bisphosphonates therapy still remains unclear. Well-designed, adequately-powered, placebo-controlled RCTs investigating the effects of oral bisphosphonates on fractures reduction and improvement in quality of life in both children and adults are studied here.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 32589343
DOI: 10.1111/os.12611 -
Clinical Oral Investigations Aug 2023To investigate the histomorphometric changes occurring in alveolar ridge preservation (ARP) based on the use of different plasma concentrates (PCs) in randomized... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To investigate the histomorphometric changes occurring in alveolar ridge preservation (ARP) based on the use of different plasma concentrates (PCs) in randomized clinical trials (RCT). There is controversy whether the placement of PCs in ARP is effective in the formation of new bone.
MATERIALS AND METHODS
A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: In patients undergoing tooth extraction followed by ARP, do PCs alone in the post-extraction socket in comparison with spontaneous healing improve new vital bone formation percentage in histomorphometric analysis after more than 10 weeks? The risk of bias was assessed and a meta-analysis was conducted.
RESULTS
Of 3809 results, 8 studies were considered suitable for inclusion. A total of 255 teeth were extracted in 250 patients. Regarding the PCs used, ARP was performed with platelet- and leukocyte-rich fibrin (L-PRF) in 120 sockets, and with pure platelet-rich plasma (P-PRP) in 31 sockets and 104 sockets were controlled. PCs improved new bone formation in ARP with respect to the spontaneous healing group (SMD = 1.77, 95%C.I. = 1.47-2.06, p-value < 000.1). There were no differences between the different PCs (L-PRF and P-PRP).
CONCLUSION
The results of this meta-analysis support the efficacy of the use of PCs in new bone formation in ARP. With respect to the different types of PCs studied, no differences were observed.
CLINICAL RELEVANCE
When planning implant surgery after tooth extraction, treatment with PCs should be considered for ARP. Any PC increases new bone formation compared to spontaneous healing.
Topics: Humans; Tooth Socket; Alveolar Process; Osteogenesis; Tooth; Platelet-Rich Plasma; Tooth Extraction; Fibrin; Alveolar Ridge Augmentation
PubMed: 37439800
DOI: 10.1007/s00784-023-05126-8 -
Journal of Biomedical Materials... Nov 2016This systematic review and meta-analysis evaluated the influence of biological implant surface coatings on periimplant bone formation in comparison to an uncoated... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the influence of biological implant surface coatings on periimplant bone formation in comparison to an uncoated titanium reference surface in experimental large animal models. The analysis was structured according to the PRISMA criteriae. Of the1077 studies, 30 studies met the inclusion criteriae. Nineteen studies examined the bone implant contact (BIC) and were included in the meta-analysis. Overall, the mean increase in BIC for the test surfaces compared to the reference surfaces was 3.7 percentage points (pp) (95% CI -3.9-11.2, p = 0.339). Analyzing the increase in BIC for specific coated surfaces in comparison to uncoated reference surfaces, inorganic surface coatings showed a significant mean increase in BIC of 14.7 pp (95% CI 10.6-18.9, p < 0.01), extracellular matrix (ECM) surface coatings showed an increase of 10.0 pp (95% CI 4.4-15.6, p < 0.001), and peptide coatings showed a statistical trend with 7.1 pp BIC increase (95% CI -0.8-15.0, p = 0.08). In this review, no statistically significant difference could be found for growth factor surface coatings (observed difference -3.3 pp, 95% CI -16.5-9.9, p = 0.6). All analyses are exploratory in nature. The results show a statistically significant effect of inorganic and ECM coatings on periimplant bone formation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2898-2910, 2016.
Topics: Animals; Bone Substitutes; Coated Materials, Biocompatible; Implants, Experimental; Intercellular Signaling Peptides and Proteins; Osteogenesis; Surface Properties; Titanium
PubMed: 27301790
DOI: 10.1002/jbm.a.35805 -
Stem Cells International 2021Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of... (Review)
Review
Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy to enhance bone regeneration. Growing evidence suggests that macrophages have a significant impact on osteogenesis during bone regeneration. However, the precise mechanisms by which macrophage subtypes influence bone regeneration and how MSCs communicate with macrophages have not yet been fully elucidated. In this systematic literature review, we gathered evidence regarding the crosstalk between MSCs and macrophages during bone regeneration. According to the PRISMA protocol, we extracted literature from PubMed and Embase databases by using "mesenchymal stem cells" and "macrophages" and "bone regeneration" as keywords. Thirty-three studies were selected for this review. MSCs isolated from both bone marrow and adipose tissue and both primary macrophages and macrophage cell lines were used in the selected studies. In conclusion, anti-inflammatory macrophages (M2) have significantly more potential to strengthen bone regeneration compared with naïve (M0) and classically activated macrophages (M1). Transplantation of MSCs induced M1-to-M2 transition and transformed the skeletal microenvironment to facilitate bone regeneration in bone fracture and bone defect models. This review highlights the complexity between MSCs and macrophages, providing more insight into the polarized macrophage behavior in this evolving field of osteoimmunology. The results may serve as a useful reference for definite success in MSC-based therapy based on the critical interaction with macrophages.
PubMed: 34221025
DOI: 10.1155/2021/8835156 -
Bioscience Reports Jan 2021In the skeletal system, blood vessels not only function as a conduit system for transporting gases, nutrients, metabolic waste, or cells but also provide multifunctional...
In the skeletal system, blood vessels not only function as a conduit system for transporting gases, nutrients, metabolic waste, or cells but also provide multifunctional signal molecules regulating bone development, regeneration, and remodeling. Endothelial cells (ECs) in bone tissues, unlike in other organ tissues, are in direct contact with the pericytes of blood vessels, resulting in a closer connection with peripheral connective tissues. Close-contact ECs contribute to osteogenesis and osteoclastogenesis by secreting various cytokines in the paracrine or juxtacrine pathways. An increasing number of studies have revealed that extracellular vesicles (EVs) derived from ECs can directly regulate maturation process of osteoblasts and osteoclasts. The different pathways focus on targets at different distances, forming the basis of the intimate spatial and temporal link between bone tissue and blood vessels. Here, we provide a systematic review to elaborate on the function of ECs in bone biology and its underlying mechanisms based on three aspects: paracrine, EVs, and juxtacrine. This review proposes the possibility of a therapeutic strategy targeting blood vessels, as an adjuvant treatment for bone disorders.
Topics: Bone Diseases; Bone and Bones; Cytokines; Endothelium, Vascular; Extracellular Vesicles; Humans; Osteoblasts; Osteoclasts
PubMed: 33403387
DOI: 10.1042/BSR20203258 -
Journal of Nanobiotechnology Apr 2024Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on... (Review)
Review
Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research.
Topics: Osteogenesis; Endothelial Cells; Bone Regeneration; Osteoclasts; Nanostructures; Cell Differentiation
PubMed: 38627717
DOI: 10.1186/s12951-024-02442-3 -
International Journal of Clinical... 2021Determine the benefits of low-level laser therapy (LLLT) as a complement to rapid maxillary expansion (RME), through a systematic review. (Review)
Review
AIM AND OBJECTIVE
Determine the benefits of low-level laser therapy (LLLT) as a complement to rapid maxillary expansion (RME), through a systematic review.
BACKGROUND
Transversal maxillary compression is a common skeletal problem that can be treated with different devices. This RME technique consists of the separation and regeneration of the midpalatal suture. Low-level laser therapy has been suggested to be able to accelerate bone healing after trauma or bone defects.
REVIEW RESULTS
Thirty-two publications were found by electronic search during July to August of 2019 on Medline (PubMed) and Google Scholar, using the terms "", ", "", and "O". Only 16 were used (2 systematic reviews, 6 articles on humans, and 8 on animals). Even though all the studies had different intervention protocols, they all revealed that LLLT has the effect of accelerating bone regeneration after RME.
CONCLUSION
The use of LLLT as a complement to RME has shown promising results with cellular biostimulation, promoting angiogenesis and bone regeneration of the midpalatal suture.
CLINICAL SIGNIFICANCE
This study provides scientific evidence of the benefits of using LLLT as a complement to RME during orthopedic and orthodontic treatments, accelerating bone regeneration and reducing the time of consolidation of the maxillary.
HOW TO CITE THIS ARTICLE
Lai P-S, Fierro C, Bravo L, Benefits of Using Low-level Laser Therapy in the Rapid Maxillary Expansion: A Systematic Review. Int J Clin Pediatr Dent 2021;14(S-1):S101-S106.
PubMed: 35082475
DOI: 10.5005/jp-journals-10005-1966