PARAGEN · Biomaterials with incorporated MSC-secreted PARAcrine molecules for bone reGENeration
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-03-20 → 2020-03-19
- EU contribution
- €246,668
- Participants
- 2
- Scheme
- MSCA-IF-GF
Lines connect the coordinator with its partners.
Results in brief
Biomaterials with incorporated MSC-secreted PARAcrine molecules for bone reGENeration
Regeneration of bone defects caused by trauma, resection of tumors, or metabolic bone diseases remains a critical challenge in orthopaedics. Mesenchymal stromal cell (MSC) therapy with biomaterials show huge promise for bone repair. After transplantation, MSCs can act as mediators of bone formation by the secretion of paracrine factors. Importantly, it appears that delivery of cells themselves may not be required for therapeutic benefit. When MSCs are cultured in vitro they release paracrine factors into their conditioned media (MSC-CM) including cytokines and extracellular vesicles. The scientific aim of the PARGEN project is to investigate the paracrine factors secreted by MSCs and their role in tissue regeneration. Specifically, these objectives included the exploration of the MSC secretome when cultured in various environments in vitro. The optimisation of the collection and isolation of MSC secreted factors was performed. MSCs cultured in vitro on calcium phosphates and the impact of these biomaterials on the healing capacity of the MSCs and the effects of the MSC secretome was investigated.Together, these studies revealed that the culture microenvironment, in particular the mechanical properties and topography of MSC substrates greatly affects the secretion of factors by MSCs and in turn their impact on cells involved in bone tissue healing. These results have been disseminated through conference talks and seminars and will be presented in peer reviewed articles.
Data: CORDIS, © European Union
Project objective
Regeneration of bone defects remains a critical challenge in orthopaedics. Mesenchymal stromal cells (MSC) with biomaterials show huge promise for bone regeneration. However, MSC die shortly after implantation and act as mediators, by secretion of paracrine factors (PF), rather than effectors of bone formation. Importantly, it seems that delivery of cells themselves may not be required for therapeutic benefit. When MSC are cultured in vitro they release PF into their conditioned media (MSC-CM) including cytokines and extracellular vesicles. The goal of this project is to prepare novel biomaterials which are loaded with MSC-CM for in situ bone tissue engineering. PF secreted into MSC-CM during normoxia, hypoxia, and cell death will be measured. Biomaterials (biphasic calcium phosphate ceramics) will be functionalized with MSC-CM by using the polyelectrolyte multi-layering (PEM) method. The biocompatibility, release kinetics, and potential of MSC-CM loaded biomaterials for bone regeneration will be tested in vitro on cells involved in bone formation (MSC, monocytes, osteoclasts, macrophages, and endothelial cells) and in vivo by implanting the biomaterials in subcutis sites and segmented femoral defects in nude mice. Importantly, the delivery of MSC-CM can overcome the donor-dependent variability in bone formation associated with MSC cell therapy and permits a more straightforward transfer of this therapy to clinical treatment. Since MSC-CM is devoid of cells and doesn’t carry patient rejection risk, autologous MSC are not required. Therefore, selected MSC that successfully induce bone formation can be used to collect potent MSC-CM which can be loaded onto biomaterials for therapeutic use in countless patients. An ‘off-the-shelf’ product that could harness the benefits of MSC therapy but circumvent the costly and time consuming multi-step procedures involved with MSC implantation would be of immense interest to the bone regeneration field.
Original text from CORDIS.
Participants
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisCoordinatorFrance
- PRESIDENT AND FELLOWS OF HARVARD COLLEGE · CambridgeUnited States
Links
Data: CORDIS, © European Union