Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial

Gómez‐Barrena, Enrique; Rosset, Philippe; Gebhard, Florian; Hernigou, Philippe; Baldini, Nicola; Rouard, Hélène; Sensebé, Luc; Gonzalo-Daganzo, Rosa M.; Giordano, Rosaria; Padilla-Eguiluz, Norma G.; García-Rey, Eduardo; Cordero‐Ampuero, José; Rubio-Suárez, Juan Carlos; Stanovici, Julien; Ehrnthaller, Christian; Huber‐Lang, Markus; Flouzat-Lachaniette, Charles-Henri; Chevallier, Nathalie; Donati, Davide María; Ciapetti, G.; Fleury-Cappellesso, Sandrine; Fernández, M.N.; Cabrera, José Rafael; Avendaño-Solá, Cristina; Montemurro, Tiziana; Panaitescu, Carmen; Veronesi, Elena; Rojewski, Markus; Lotfi, Ramin; Dominici, Massimo; Schrezenmeier, Hubert; Layrolle, Pierre

doi:10.1016/j.biomaterials.2018.03.033

Cited by 91 publications

(58 citation statements)

References 16 publications

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“…Most recently, significant regeneration (in both horizontal and vertical dimensions) for severe mandibular resorption has been reported when bone marrow stromal stem cells were used in conjunction with biphasic calcium phosphate scaffolds and titanium‐reinforced membranes (Gjerde et al., ). Similar results have been reported when using similar procedures for treating orthopaedic non‐unions (Gomez‐Barrena et al., ). All human clinical studies to date have demonstrated that bone regeneration requires MSC to have a suitable environment, and this is usually facilitated by the use of appropriate scaffold as well as biologic factors such as bone morphogenetic proteins (BMPs), transforming factor‐beta and insulin‐like growth factor.…”

Section: Mesenchymal Stem Cells and Bone Regenerationsupporting

confidence: 86%

Mesenchymal stem cells and biologic factors leading to bone formation

Bartold

Gronthos

Haynes

et al. 2019

J Clinic Periodontology

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Background Physiological bone formation and bone regeneration occurring during bone repair can be considered distinct but similar processes. Mesenchymal stem cells (MSC) and associated biologic factors are crucial to both bone formation and bone regeneration. Aim To perform a narrative review of the current literature regarding the role of MSC and biologic factors in bone formation with the aim of discussing the clinical relevance of in vitro and in vivo animal studies. Methods The literature was searched for studies on MSC and biologic factors associated with the formation of bone in the mandible and maxilla. The search specifically targeted studies on key aspects of how stem cells and biologic factors are important in bone formation and how this might be relevant to bone regeneration. The results are summarized in a narrative review format. Results Different types of MSC and many biologic factors are associated with bone formation in the maxilla and mandible. Conclusion Bone formation and regeneration involve very complex and highly regulated cellular and molecular processes. By studying these processes, new clinical opportunities will arise for therapeutic bone regenerative treatments.

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Section: Mesenchymal Stem Cells and Bone Regenerationsupporting

confidence: 86%

Mesenchymal stem cells and biologic factors leading to bone formation

Bartold

Gronthos

Haynes

et al. 2019

J Clinic Periodontology

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“…For example, focusing on BM‐derived MSCs, it is now established that starting from 20 ml of marrow aspirate shipped overnight from the clinic to the cell manufacturing site, MSCs can be isolated and amplified to up to hundreds of millions of cells in less than 1 month. Cells can then be shipped back to the operating room for surgical implantation alone or even in combination with biomaterials for skeletal disorders .…”

Section: Learning From More Than 50 Years Of Msc Investigationsmentioning

confidence: 99%

Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review

Mastrolia

Foppiani

Murgia

et al. 2019

Stem Cells Translational Medicine

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190

158

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Summary Identified 50 years ago, mesenchymal stromal/stem cells (MSCs) immediately generated a substantial interest among the scientific community because of their differentiation plasticity and hematopoietic supportive function. Early investigations provided evidence of a relatively low engraftment rate and a transient benefit for challenging congenital and acquired diseases. The reasons for these poor therapeutic benefits forced the entire field to reconsider MSC mechanisms of action together with their ex vivo manipulation procedures. This phase resulted in advances in MSCs processing and the hypothesis that MSC‐tissue supportive functions may be prevailing their differentiation plasticity, broadening the spectrum of MSCs therapeutic potential far beyond their lineage‐restricted commitments. Consequently, an increasing number of studies have been conducted for a variety of clinical indications, revealing additional challenges and suggesting that MSCs are still lagging behind for a solid clinical translation. For this reason, our aim was to dissect the current challenges in the development of still promising cell types that, after more than half a century, still need to reach their maturity. Stem Cells Translational Medicine 2019;8:1135–1148

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“…Nevertheless, successful regeneration in both horizontal and vertical dimensions was reported in 11 patients treated with BMSC‐loaded BCP scaffolds contained by a titanium‐reinforced membrane (Gjerde et al., ). A similar strategy was successfully applied in the treatment of orthopaedic non‐unions in a recent multicenter trial (Gómez‐Barrena et al., ). Both studies included a highly standardized laboratory protocol for cell manufacturing and provide examples of successful regeneration in challenging bone deficiencies.…”

Section: Discussionmentioning

confidence: 99%

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Shanbhag

Suliman

Pandis

et al. 2019

J Clinic Periodontology

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Aim The objective of the present review was to answer the focused question: what is the effect of cell therapy in terms of orofacial bone regeneration compared to grafting with only biomaterial scaffolds and/or autogenous bone? Methods Electronic databases were searched for relevant controlled clinical and pre‐clinical (large‐animal) studies. Separate meta‐analyses of quantitative data regarding histological or radiographic new bone formation were performed. Results Forty‐seven eligible clinical and 57 pre‐clinical studies were included. Clinical studies were categorized based on the use of “minimally manipulated” whole tissues (e.g., bone marrow) or ex vivo expanded cells from “uncommitted” (bone marrow, adipose tissue) or “committed” sources (periosteum, bone). Based on limited and heterogeneous clinical evidence, implantation of cells (mostly whole bone marrow), in combination with biomaterial scaffolds results in bone regeneration which is (a) superior compared to implantation of scaffolds alone in sinus and horizontal ridge augmentation, and (b) comparable to autogenous bone in alveolar cleft repair. Conclusions Although current evidence points to the benefits of cell therapy in certain clinical indications, it is unclear whether the use of ex vivo expanded cells, either uncommitted or committed, is superior to whole tissue fractions in terms of bone regeneration. The relatively larger effect sizes in favour of cell therapy observed in pre‐clinical studies are diminished in clinical trials. Future controlled studies should include cost‐effectiveness analyses to guide clinical decision‐making.

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Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial

Abstract: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).

Cited by 91 publications

References 16 publications

Mesenchymal stem cells and biologic factors leading to bone formation

Mesenchymal stem cells and biologic factors leading to bone formation

Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

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