Engineering and Cellular Therapy Unit

Créteil, France

Engineering and Cellular Therapy Unit

Créteil, France
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Mebarki M.,French Institute of Health and Medical Research | Mebarki M.,University Paris Est Creteil | Mebarki M.,Engineering and Cellular Therapy Unit | Coquelin L.,French Institute of Health and Medical Research | And 16 more authors.
Acta Biomaterialia | Year: 2017

In order to induce an efficient bone formation with human bone marrow mesenchymal stromal cells (hBMSC) associated to a scaffold, it is crucial to determine the key points of the hBMSC action after in vivo transplantation as well as the appropriate features of a scaffold. To this aim we compared the hBMSC behavior when grafted onto two biomaterials allowing different bone potential in vivo. The cancellous devitalized Tutoplast®-processed bone (TPB) and the synthetic hydroxyapatite/β-tricalcium-phosphate (HA/βTCP) which give at 6. weeks 100% and 50% of bone formation respectively. We first showed that hBMSC adhesion is two times favored on TPB in vitro and in vivo compared to HA/βTCP. Biomaterial structure analysis indicated that the better cell adhesion on TPB is associated to its higher and smooth open pore architecture as well as its content in collagen. Our 6. week time course analysis, showed using qPCR that only adherent cells are able to survive in vivo giving thus an advantage in term of cell number on TPB during the first 4. weeks after graft. We then showed that grafted hBMSC survival is crucial as cells participate directly to bone formation and play a paracrine action via the secretion of hIGF1 and hRANKL which are known to regulate the bone formation and resorption pathways respectively. Altogether our results point out the importance of developing a smooth and open pore scaffold to optimize hBMSC adhesion and ensure cell survival in vivo as it is a prerequisite to potentiate their direct and paracrine functions. Statement of Significance: Around 10% of skeletal fractures do not heal correctly causing nonunion. An approach involving mesenchymal stromal cells (MSC) associated with biomaterials emerges as an innovative strategy for bone repair. The diversity of scaffolds is a source of heterogeneity for bone formation efficiency. In order to better determine the characteristics of a powerful scaffold it is crucial to understand their relationship with cells after graft. Our results highlight that a biomaterial architecture similar to cancellous bone is important to promote MSC adhesion and ensure cell survival in vivo. Additionally, we demonstrated that the grafted MSC play a direct role coupled to a paracrine effect to enhance bone formation and that both of those roles are governed by the used scaffold. © 2017 Acta Materialia Inc.


Coquelin L.,University Paris Est Creteil | Coquelin L.,Engineering and Cellular Therapy Unit | Fialaire-Legendre A.,Engineering and Cellular Therapy Unit | Roux S.,University Paris Est Creteil | And 14 more authors.
Tissue Engineering - Part A | Year: 2012

Bone allografts are commonly used by orthopedists to provide a mechanical support and template for cellular colonization and tissue repair. There is an increasing demand for bone graft substitutes that are safe and easy to store but which are equally effective in supporting new bone growth. In this study, we compared three different human bone allografts: (1) the cryopreserved allograft (frozen), (2) the gamma-irradiated and cryopreserved allograft (γ-irradiated), and (3) the solvent dehydrated and γ-irradiated- processed bone allograft (Tutoplast® Process Bone [TPB]). Human mesenchymal stromal cells (hMSCs) have the potential to differentiate into osteogenic, chondrogenic, and adipogenic lineages. Our results showed that hMSC seeding efficiency was equivalent among the three bone allografts. However, differences were observed in terms of cell metabolism (viability), osteoblastic gene expression, and in vivo bone formation. Frozen allografts had the higher frequency of new bone formation in vivo (89%). Compared with frozen allografts, we demonstrated that TPB allografts allowed optimal hMSC viability, osteoblastic differentiation, and bone formation to occur in vivo (72%). Further, the frequency of successful bone formation was higher than that obtained with the γ-irradiated allograft (55%). Moreover, after hMSC osteoinduction, 100% of the TPB and frozen allografts formed bone in vivo whereas only 61% of the γ-irradiated allografts did. As healthcare teams around the world require bone-grafting scaffolds that are safe and easy to store, the TPB allograft appears to be a good compromise between efficient bone formation in vivo and convenient storage at room temperature. © Copyright 2012, Mary Ann Liebert, Inc.

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