Biomarkers of bone healing induced by a regenerative approach based on expanded bone marrow–derived mesenchymal stromal cells

Granchi, Donatella; Ciapetti, G.; Gómez‐Barrena, Enrique; Rojewski, Markus; Rosset, Philippe; Layrolle, Pierre; Spazzoli, Benedetta; Donati, Davide María; Baldini, Nicola

doi:10.1016/j.jcyt.2019.06.002

Cited by 11 publications

(21 citation statements)

References 66 publications

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“…CTX is the most abundant form of collagen in the human body and is the only collagen component in bone, accounting for more than 90% of bone matrix. CTX plays an important role in osteoporotic fracture and has a high predictive value for osteoporotic fracture; therefore, it is used as a marker of bone resorption [36]. In the present study, various indicators in serum were detected.…”

Section: Discussionmentioning

confidence: 65%

Effect of Sleeve Gastrectomy on Bone Metabolism and Serum 5-Hydroxytryptamine in Obese Rats

Liu

et al. 2020

Med Sci Monit

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Background:Studies have shown that bariatric surgery, such as sleeve gastrectomy (SG), has an adverse effect on bone, including decreased bone mineral density (BMD) and bone metabolism. Peripheral 5-hydroxytryptamine (5-HT) has an adverse regulatory effect on bone formation. Here, we assessed changes in bone metabolism and whether 5-HT is involved in the effect of SG on bone metabolism. Material/Methods:A rat model of obesity was established using Wistar rats. After successful modeling, rats were randomly assigned to 2 groups -the SG group and the Sham group -with 10 rats in each group. We then performed sleeve gastrectomy or sham operation. Bone metabolic markers and BMD of rats were measured at 2 and 16 weeks after the operation and the level of 5-HT in serum was determined. Rats were killed at 16 weeks after the operation, and bones of the hind limbs were harvested to measure 5-HT by immunofluorescence. Results:BMD was decreased and bone metabolism demonstrated a trend of bone destruction in the rats after SG. A significantly increasing trend in the level of serum 5-HT was found, and bone immunofluorescence showed increased expression of 5-HT. Conclusions:BMD was decrease and bone metabolism demonstrated a trend of bone destruction after SG. SG can affect the level of 5-HT in serum or bone tissue and the 5-HT may be involved in the process through which SG affects bone metabolism.

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Section: Discussionmentioning

confidence: 65%

Effect of Sleeve Gastrectomy on Bone Metabolism and Serum 5-Hydroxytryptamine in Obese Rats

Liu

et al. 2020

Med Sci Monit

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“…Therefore, compared to other cell therapy-related treatments, this method has the advantage of convenience. BMA mainly has three application strategies, including intraoperative injection, transplantation after in vitro expansion, and soaked ACB or other bone graft materials [ 47 , 48 ]. However, osteofascial compartment syndrome after multiple injections should be especially considered.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials

Yang

Zhang

Liang

et al. 2022

BMC Musculoskelet Disord

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Background Fracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis. Methods A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions. Results Thirty studies were included in the analysis. For the healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA + ACB (90%), and BMA alone (82%) showed relative advantages in the healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (SMD: -9.26; 95% CI: − 14.64, − 3.87). LIUS (100%), BMA + PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Compared with the control, electromagnetic field (EMF) (OR: 13.21; 95% CI: 1.58, 110.40) and extracorporeal shock wave (ESWT) (OR: 4.90; 95% CI: 1.38, 17.43) had a higher AE risk. Conclusions Among the current intervention strategies, BMA in combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. EMF and ESWT may have a high risk of AE. However, large-scale, well-designed studies are still needed to confirm the results. Trial registration Retrospectively registered.

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“…In contrast, in our study we only included patients suffering from non-hypertrophic pseudoarthrosis. In a recently published paper, Granchi and collaborators assessed different biomarkers in aseptic pseudoarthrosis surgically treated with a tissue engineering product in the context of a clinical trial, with a study design similar to ours (namely: C-Propetide of Type I Procollagen, CICP; C-terminal telopeptide of type I collagen, CTX; Bone isoform of Alkaline Phosphatase, BAP; Nterminal/midregion fragment of Osteocalcin, N-Mid OC; Osteoprotegerin, OPG; Receptor Activator of Nuclear Factor-κB ligand, RANKL) ( Granchi et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that pseudoarthrosis is not a prevalent pathology (especially in our case, focusing on non-hypertrophic pseudoarthrosis with restrictive inclusion criteria) and large samples are extremely difficult to recruit, in our case, patient recruitment took 4 years in one single centre. Alternatively, multi-centre studies, as described by Granchi and collaborators, may be a solution for future research ( Granchi et al, 2019 ). We also observed a gender bias in the treated population (17 male vs. 3 female), although this was probably due to the casuistry, provided that no evidence of gender-dependency has been described in the literature for bone healing.…”

Section: Discussionmentioning

confidence: 99%

A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones

et al. 2022

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Background Pseudoarthrosis or non-union is a complication with an incidence of 5–10% of bone fractures, most frequently located in the diaphysis of long bones. The management of this complication is addressed by means of complex surgical procedures and is a concern for orthopaedic and trauma surgeons nowadays. The use of biomarkers for diagnosing patients at risk of non-union would help us to establish special measures for early corrective treatment. Methods Prospective exploratory pilot study with a cohort of 20 patients diagnosed of non-hypertrophic pseudoarthrosis of long bones who were treated surgically with either autologous bone graft or a Tissue Engineering Product composed of bone marrow-derived Mesenchymal Stromal Cells. Patients were followed for 12 months and plasma blood samples were obtained to determine circulating levels of Transforming Growth Factor Beta 1 and Beta 2 (TGF-β1 and TGF-β2, respectively) at inclusion, and at 1 week, 2 weeks, and months 1, 2, 3, 6 and 12 after surgery. Radiological bone healing was evaluated by the Tomographic Union Score (TUS). Results Basal levels of TGF-β1 and TGF-β2 were determined in the twenty patients (26,702 ± 14,537 pg/mL and 307.8 ± 83.1 pg/mL, respectively). Three of them withdrew from the study, so complete follow-up was conducted on 17 patients (9 successfully healed vs. 8 that did not heal). Statistically significant differences between the bone healing group and the non-union group were found at month 12 for both TGF-β1 ( p = 0.005) and TGF-β2 ( p = 0.02). Conclusions TGF-β1 and TGF-β2 are biomarkers that correlate with clinical evidence of bone regeneration and may be used to monitor patients, although early predictive value after intervention needs to be further studied in combination with other molecules.

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Biomarkers of bone healing induced by a regenerative approach based on expanded bone marrow–derived mesenchymal stromal cells

Cited by 11 publications

References 66 publications

Effect of Sleeve Gastrectomy on Bone Metabolism and Serum 5-Hydroxytryptamine in Obese Rats

Effect of Sleeve Gastrectomy on Bone Metabolism and Serum 5-Hydroxytryptamine in Obese Rats

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials

A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones

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