Bone formation by human paediatric marrow stromal cells in a functional allogeneic immune system

Allogeneic stem-cell based regenerative medicine is a promising approach for bone defect repair. The use of chondrogenically differentiated human marrow stromal cells (MSCs) has been shown to lead to bone formation by endochondral ossification in immunodeficient pre-clinical models. However, an insi...

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Bibliographic Details
Published in:Biomaterials 2024-04, Vol.306, p.122471-122471, Article 122471
Main Authors: Palomares Cabeza, Virginia, Fahy, Niamh, Kiernan, Caoimhe H., Lolli, Andrea, Witte-Bouma, Janneke, Fahmy Garcia, Shorouk, Merino, Ana, Kops, Nicole, Ridwan, Yanto, Wolvius, Eppo B., Brama, Pieter A.J., Hoogduijn, Martin J., Farrell, Eric
Format: Article
Language:English
Subjects:
Allogeneic
Animals
Bone
Bone Marrow
Bone Marrow Cells
Cell Differentiation
Cells, Cultured
Child
Endochondral ossification
Hematopoietic Stem Cell Transplantation
Humans
Mesenchymal stem cell/marrow stromal cell
Mesenchymal Stem Cells
Mice
Osteogenesis
Stromal Cells
Tissue Engineering
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Summary:Allogeneic stem-cell based regenerative medicine is a promising approach for bone defect repair. The use of chondrogenically differentiated human marrow stromal cells (MSCs) has been shown to lead to bone formation by endochondral ossification in immunodeficient pre-clinical models. However, an insight into the interactions between the allogeneic immune system and the human MSC-derived bone grafts has not been fully achieved yet. The choice of a potent source of MSCs isolated from pediatric donors with consistent differentiation and high proliferation abilities, as well as low immunogenicity, could increase the chance of success for bone allografts. In this study, we employed an immunodeficient animal model humanised with allogeneic immune cells to study the immune responses towards chondrogenically differentiated human pediatric MSCs (ch-pMSCs). We show that ch-differentiated pMSCs remained non-immunogenic to allogeneic CD4 and CD8 T cells in an in vitro co-culture model. After subcutaneous implantation in mice, ch-pMSC-derived grafts were able to initiate bone mineralisation in the presence of an allogeneic immune system for 3 weeks without the onset of immune responses. Re-exposing the splenocytes of the humanised animals to pMSCs did not trigger further T cell proliferation, suggesting an absence of secondary immune responses. Moreover, ch-pMSCs generated mature bone after 8 weeks of implantation that persisted for up to 6 more weeks in the presence of an allogeneic immune system. These data collectively show that human allogeneic chondrogenically differentiated pediatric MSCs might be a safe and potent option for bone defect repair in the tissue engineering and regenerative medicine setting.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2024.122471