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Title Use of Bone Marrow-Derived Mononuclear Cell Concentrate as an Adjuvant to Maxillary Sinus Augmentation (MSA) Does Not Improve Bone Formation Over Conventional MSA with Acellular Bone Matrix Graft Alone
Clinical Question In otherwise healthy adults undergoing maxillary sinus augmentation (MSA) with acellular bone matrix material, does the addition of autologous bone marrow-derived mononuclear cell concentrate into the graft site improve new bone formation compared to use of acellular bone matrix material alone?
Clinical Bottom Line A conventional MSA utilizing acellular bone matrix material (e.g. allograft [AlloOss, Osteocel, Oral Bone], xenografts [Bio-Oss, Bovine Bone Matrix (BBM)], alloplastic [e.g. polylactid-co-glycolic acid (PLGA) copolymer, Biocoral, calcium phosphate]) can effectively increase bone volume in the posterior maxilla. Results indicate that adjuvant delivery of bone marrow-derived mononuclear cells (containing mesenchymal stem cells) during MSA only marginally improves bone regrowth over MSA using acellular bone material alone.
Best Evidence (you may view more info by clicking on the PubMed ID link)
PubMed ID Author / Year Patient Group Study type
(level of evidence)
#1) 23313230Mangano/201361 adult patients in 2 RCTs and 2 case control studiesMeta-Analysis
Key resultsA quantitative meta-analysis of 4 RCTs calculated a +3.3% weighted mean difference estimate from a random-effects model (95% CI, -5.9% to 12.5%), which demonstrates "a marginal, nonstatistically significant positive effect of stem cells on bone regrowth."
#2) 23834336Jakobsen/201361 adult patients in 2 RCTs and 2 case control studiesSystematic review of randomized trials
Key resultsRickert et al. 2010 indicated a 5.7% increase in bone with MSCs present. Sauerbier et al. 2011 reported similar histological findings between conventional MSA and MSA with concentrated mononuclear cells by bone marrow aspirate concentrate (BMAC). Mangano et al 2009 indicated that the conventional MSA site with porous calcium phosphate (Biocoral) produced more vertical bone height (9.14 mm) and bone volume (54.65% +/- 21.17%) than the MSA site with bioengineered bone (mandible bone marrow aspirate & PGLA scaffold) alone (vertical height = 6.47 mm and bone volume 37.32% +/-19.59%). Gonshor et al. 2011 indicated more vital bone content from the MSC-containing cellular graft material Osteocel (32.5% +/-6.8%) than with the aceullar cancellous particulate allograft bone graft material AlloOss (18.3% +/- 10.6%).
Evidence Search mesenchymal[Title] AND stem[Title] AND cells[Title] AND maxillary[Title] AND sinus[Title] AND augmentation[Title]
Comments on
The Evidence
Validity: Both the Mangano et al. 2013 meta-analysis and Jakobson et al. 2013 systematic review highlight 4 available RCTs that utilized bone marrow cell-based MSA approaches with acelluar scaffolds (61 adult patients undergoing MSA: Rickert et al. 2010, Sauerbier et al. 2011, Mangano et al 2009, and Gonshor et al. 2011). In these studies, a total of 98 MSAs (42 bilateral, 14 unilateral) were analyzed to compare cell graft adjuvant treatment (performed in 64 MSAs) to conventional control MSA grafts (performed in 34 MSAs). The Rickert et al. 2010 study was a split-mouth study of 12 patients with 11 of 12 patients included in data analysis (91% completion rate). The Sauerbier et al. 2011 study involved 40 patients, but only 26 remained eligible for inclusion in data analysis (65% completion rate). Of the 26 patients that met inclusion criteria (45 sinuses), 34 sinuses received cellular treatments and 11 received control treatment. The Mangano et al 2009 study was a split-mouth study of 5 patients, and all 5 patients completed the study (100% completion rate). The Gonshor et al. 2011 study consisted of 18 patients (8 bilateral, 10 unilateral) with 26 sinus augmentations performed. Only 5 MSAs (3 unilateral MSAs and 1 bilateral) were excluded from data analysis (14/18 patients, 78% completion rate). All four of these studies used a variety of study parameters, but each utilized an acellular matrix and a cellular adjuvant containing mesenchymal stem cells. All 4 RCTs had MSA independent of implant placement and histological analysis of bone quality at the time of implant placement and between 3-6 months post-MSA. The work of Mangano et al. 2013 attempted to pool these studies to determine a meaningful summary analysis (meta-analysis). No conflict of interest was reported form the 4 RCTs studies, the Mangano et al. 2013 meta-analysis, or the Jakobson et al. 2013 systematic review. Perspective: Mangano et al. 2013 and Jakobson et al. 2013 report similar findings due to their common reliance on the same four articles (4 RCTs) for evaluation of bone marrow-derived mononuclear cell concentrate compared to conventional acellular graft material. When interpreting the data, it is important to consider a cost/benefit analysis of cell adjuvant MSA compared to MSA alone.
Applicability For patients who have inadequate bone volume in the posterior maxilla for dental implant placement, conventional MSA with an acellular bone matrix is a proven option for augmenting maxillary bone prior to implant placement. The success of an acellular bone graft depends on cell infiltration and vascularization in order to produce viable replacement bone. It has been proposed that local delivery of a concentration of mesenchymal stem cells (MSCs) into a bone graft site, such as the maxillary sinus space, may accelerate the integration of bone graft material by providing increased MSCs that can differentiate to form active osteoblasts in the bony site rather than waiting for cellular and vascular recruitment to occur in the graft site. Current evidence, however, demonstrates that when mononuclear cell concentrate (containing MSCs) is added as an adjuvant to conventional MSA using acellular bone graft, only marginal clinical (and statistically insignificant) improvements in bone growth are seen. Additionally, use of a conventional acellular MSA approach alone avoids a donor site surgery to harvest bone marrow aspirate from the iliac crest (aspirate is then processed to isolate a mononuclear cell fraction). Therefore when maxillary bone augmentation is considered, conventional MSA with acellular bone graft material is the preferred treatment choice.
Specialty/Discipline (Oral Surgery) (Periodontics)
Keywords maxillary sinus augmentation, MSA, sinus lift, mononuclear cell concentrate, mesenchymal stem cells, xenograft, allograft, alloplastic graft
ID# 2844
Date of submission: 04/09/2015spacer
E-mail Farnsworth@livemail.uthscsa.edu
Author Steven L. Farnsworth
Co-author(s) Peter J. Hornsby, PhD
Co-author(s) e-mail Hornsby@uthscsa.edu
Faculty mentor/Co-author Edward Ellis, III, DDS
Faculty mentor/Co-author e-mail ellise3@uthscsa.edu
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