Lentiviral-Mediated Integrin α5 Expression in Human Adult Mesenchymal Stromal Cells Promotes Bone Repair in Mouse Cranial and Long-Bone Defects

2012 ◽  
Vol 23 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Samer Srouji ◽  
Dror Ben-David ◽  
Olivia Fromigué ◽  
Pascal Vaudin ◽  
Gisela Kuhn ◽  
...  
Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S170
Author(s):  
S. Srouji ◽  
O. Fromigué ◽  
P. Vaudin ◽  
D. Ben-David ◽  
E. Livne ◽  
...  

Materials ◽  
2021 ◽  
Vol 14 (14) ◽  
pp. 3852
Author(s):  
Federica Re ◽  
Luciana Sartore ◽  
Elisa Borsani ◽  
Matteo Ferroni ◽  
Camilla Baratto ◽  
...  

Gelatin–dextran hydrogel scaffolds (G-PEG-Dx) were evaluated for their ability to activate the bone marrow human mesenchymal stromal cells (BM-hMSCs) towards mineralization. G-PEG-Dx1 and G-PEG-Dx2, with identical composition but different architecture, were seeded with BM-hMSCs in presence of fetal bovine serum or human platelet lysate (hPL) with or without osteogenic medium. G-PEG-Dx1, characterized by a lower degree of crosslinking and larger pores, was able to induce a better cell colonization than G-PEG-Dx2. At day 28, G-PEG-Dx2, with hPL and osteogenic factors, was more efficient than G-PEG-Dx1 in inducing mineralization. Scanning electron microscopy (SEM) and Raman spectroscopy showed that extracellular matrix produced by BM-hMSCs and calcium-positive mineralization were present along the backbone of the G-PEG-Dx2, even though it was colonized to a lesser degree by hMSCs than G-PEG-Dx1. These findings were confirmed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), detecting distinct lipidomic signatures that were associated with the different degree of scaffold mineralization. Our data show that the architecture and morphology of G-PEG-Dx2 is determinant and better than that of G-PEG-Dx1 in promoting a faster mineralization, suggesting a more favorable and active role for improving bone repair.


2020 ◽  
Vol 6 (10) ◽  
pp. eaaw7853 ◽  
Author(s):  
Sébastien Sart ◽  
Raphaël F.-X. Tomasi ◽  
Antoine Barizien ◽  
Gabriel Amselem ◽  
Ana Cumano ◽  
...  

Organoids that recapitulate the functional hallmarks of anatomic structures comprise cell populations able to self-organize cohesively in 3D. However, the rules underlying organoid formation in vitro remain poorly understood because a correlative analysis of individual cell fate and spatial organization has been challenging. Here, we use a novel microfluidics platform to investigate the mechanisms determining the formation of organoids by human mesenchymal stromal cells that recapitulate the early steps of condensation initiating bone repair in vivo. We find that heterogeneous mesenchymal stromal cells self-organize in 3D in a developmentally hierarchical manner. We demonstrate a link between structural organization and local regulation of specific molecular signaling pathways such as NF-κB and actin polymerization, which modulate osteo-endocrine functions. This study emphasizes the importance of resolving spatial heterogeneities within cellular aggregates to link organization and functional properties, enabling a better understanding of the mechanisms controlling organoid formation, relevant to organogenesis and tissue repair.


2012 ◽  
Vol 10 (1) ◽  
pp. 9-10 ◽  
Author(s):  
Luc Sensebé ◽  
Karin Tarte ◽  
Jacques Galipeau ◽  
Mauro Krampera ◽  
Ivan Martin ◽  
...  

2010 ◽  
Vol 16 (2) ◽  
pp. 201-214 ◽  
Author(s):  
Agnese Salvadè ◽  
Pamela Della Mina ◽  
Diego Gaddi ◽  
Francesca Gatto ◽  
Antonello Villa ◽  
...  

2017 ◽  
Vol 44 (6) ◽  
pp. 2174-2188 ◽  
Author(s):  
Fangfang Song ◽  
Hualing Sun ◽  
Liyuan Huang ◽  
Dongjie Fu ◽  
Cui Huang

Background/Aims: Human dental pulp-derived mesenchymal stromal cells (hDPSCs) are promising seed cells for tissue engineering due to their easy accessibility and multi-lineage differentiation. Pannexin3 (Panx3) plays crucial roles during bone development and differentiation. The aim of the present study was to investigate the effect of Panx3 on osteogenesis of hDPSCs and the underlying mechanism. Methods: Utilizing qRT-PCR, Western blot, and immunohistochemistry, we explored the change of Panx3 during osteogenic differentiation of hDPSCs. Next, hDPSCs with loss (Panx3 knockdown) and gain (Panx3 overexpression) of Panx3 function were developed to investigate the effects of Panx3 on osteogenic differentiation of hDPSC and the underlying mechanism. Finally, a commercial β-TCP scaffold carrying Panx3-modified hDPSCs was utilized to evaluate bone defect repair. Results: Panx3 was upregulated during osteogenic differentiation in a time-dependent manner. Panx3 overexpression promoted osteogenic differentiation of hDPSCs, whereas depletion of Panx3 resulted in a decline of differentiation, evidenced by upregulated expression of mineralization-related markers, increased alkaline phosphatase (ALP) activity, and enhanced ALP and Alizarin red staining. Panx3 was found to interact with the Wnt/β-catenin signaling pathway, forming a negative feedback loop. However, Wnt/β-catenin did not contribute to enhancement of osteogenic differentiation as observed in Panx3 overexpression. Moreover, Panx3 promoted osteogenic differentiation of hDPSCs via increasing ERK signaling pathway. Micro-CT and histological staining results showed that Panx3-modified hDPSCs significantly improved ossification of critical-sized bone defects. Conclusion: These findings suggest that Panx3 is a crucial modulator of hDPSCs differentiation.


2019 ◽  
Author(s):  
Sébastien Sart ◽  
Raphaël F.-X. Tomasi ◽  
Antoine Barizien ◽  
Gabriel Amselem ◽  
Ana Cumano ◽  
...  

AbstractOrganoids that recapitulate the functional hallmarks of anatomic structures comprise cell populations able to self-organize cohesively in 3D. However, the rules underlying organoid formation in vitro remain poorly understood because a correlative analysis of individual cell fate and spatial organization has been challenging. Here, we use a novel microfluidics platform to investigate the mechanisms determining the formation of organoids by human mesenchymal stromal cells that recapitulate the early steps of condensation initiating bone repair in vivo. We find that heterogeneous mesenchymal stromal cells self-organize in 3D in a developmentally hierarchical manner. We demonstrate a link between structural organization and local regulation of specific molecular signaling pathways such as NF-κB and actin polymerization, which modulate osteo-endocrine functions. This study emphasizes the importance of resolving spatial heterogeneities within cellular aggregates to link organization and functional properties, enabling a better understanding of the mechanisms controlling organoid formation, relevant to organogenesis and tissue repair.


2018 ◽  
Author(s):  
Ramkumar T. Annamalai ◽  
Xiaowei Hong ◽  
Nicholas Schott ◽  
Gopinath Tiruchinapally Benjamin Levi ◽  
Jan P. Stegemann

AbstractRepair of complex fractures with bone loss requires a potent, space-filling intervention to promote regeneration of bone. We present a minimally-invasive strategy combining mesenchymal stromal cells (MSC) with a chitosan-collagen matrix to form modular microtissues designed for delivery through a needle to conformally fill cavital defects. Implantation of microtissues into a calvarial defect in the mouse showed that osteogenically pre-differentiated MSC resulted in complete bridging of the cavity, while undifferentiated MSC produced mineralized tissue only in apposition to native bone. Decreasing the implant volume reduced bone regeneration, while increasing the MSC concentration also attenuated bone formation, suggesting that the cell-matrix ratio is important in achieving a robust response. Conformal filling of the defect with microtissues in a carrier gel resulted in complete healing. Taken together, these results show that modular microtissues can be used to augment the differentiated function of MSC and provide an extracellular environment that potentiates bone repair.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Pavel Šponer ◽  
Stanislav Filip ◽  
Tomáš Kučera ◽  
Jindra Brtková ◽  
Karel Urban ◽  
...  

The purpose of this prospective controlled study was to compare healing quality following the implantation of ultraporousβ-tricalcium phosphate, containing either expanded autologous mesenchymal stromal cells (trial group, 9 patients) orβ-tricalcium phosphate alone (control group, 9 patients), into femoral defects during revision total hip arthroplasty. Both groups were assessed using the Harris Hip Score, radiography, and DEXA scanning at 6 weeks and 3, 6, and 12 months postoperatively. A significant difference in the bone defect healing was observed between both groups of patients (P<0.05). In the trial group, trabecular remodeling was found in all nine patients and in the control group, in 1 patient only. Whereas, over the 12-month follow-up period, no significant difference was observed between both groups of patients in terms of the resorption ofβ-tricalcium phosphate, the significant differences were documented in the presence of radiolucency and bone trabeculation through the defect (P<0.05). Using autologous mesenchymal stromal cells combined with aβ-tricalcium phosphate scaffold is a feasible, safe, and effective approach for management of bone defects with compromised microenvironment. The clinical trial was registered at the EU Clinical Trials Register before patient recruitment has begun (EudraCT number2012-005599-33).


Author(s):  
J.S. Hanker ◽  
L.C. Hanker ◽  
B.L. Giammara

One of the biggest problems associated with the repair of trauma in long bones is their requirement to withstand greater mechanical stress than any other bones of the body. After the success we achieved with composite hydroxylapatite (HA)/plaster(PP) in craniofacial bone repair in approximately 200 animals (cats and rats) and 300 humans in our laboratory, clinics and surgeries, it was felt that an area which could perhaps benefit from our experience in bone repair might be orthopedic surgery. When first informed of our desire to apply our biomaterials interest and experience to long bone trauma patients, others expected little success with these biomaterials that were so successful in craniofacial surgery.We felt, however, that success might be achieved for long bone repair with plaster of Paris (CaSO4·½H2O) and/or calcium phosphate. The feeling of my laboratory received some support from Larry Hench's 1988 article. In this article he pointed out that bioactive ceramics such as hydroxylapatite (HA) possibly could bond to bone.


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