Stem and Progenitor Cells in Bone Regeneration

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 4177

Special Issue Editor


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Guest Editor
AO Research Institute Davos, Davos Platz, Switzerland
Interests: bone tissue regeneration/healing; stem cells and progenitor cells; tissue engineering and regenerative medicine; vascularization; biological/mechanical stimulation; intra-operative aproaches.

Special Issue Information

Dear Colleagues,

Bone possesses a remarkable innate capacity to self-repair by restoring the original biological, functional, and structural characteristics of the injured site. Bone healing occurs via the direct formation of a new bone matrix at the injured site in the case of small and fully stabilized fractures (direct or primary healing), or via the intermediate formation of a cartilaginous template aiming to stabilize the fracture site that will later remodel into new bone tissue (endochondral ossification). In both cases, stem cells are key players in the healing process and outcome. As part of the mesenchymal stromal cell population, bone-marrow-derived stem cells can differentiate toward osteogenic or chondrogenic phenotypes and are involved in direct or endochondral bone healing, respectively. The fate of stem cell differentiation during fracture healing and bone formation is regulated by many factors, such as micro-environment changes, biological signal interplay, as well as the mechanical environment and the presence or absence of surrounding blood vessels.  

While bone healing is a well-orchestrated and mainly successful process, there are numerous clinical complications that are dependent on issues such as fracture size, severity, location, and/or the lack of surrounding soft tissues/vascularization, which leads to failed or delayed healing. As only cells can produce bone, the use of cells to promote bone healing, and how their functionality and differentiation can be monitored, has been deeply investigated over the past few years. Due to their multipotency, their growth capacity, and their possible autologous isolation, stem cells are of interest for bone healing involving strategies such as cell mobilization and tissue engineering, or regenerative approaches.

For the present Special Issue, entitled "Stem and Progenitor Cells in Bone Regeneration", we aim to bring together a collection of original or review articles of basic science, preclinical, and clinical studies about stem cells in the context of bone healing and regeneration. Opinion letters, as well as articles related to regulatory considerations in the use of stem cells for bone regeneration in the clinic, are also welcome.  

Dr. Sophie Verrier
Guest Editor

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Keywords

  • stem cells
  • progenitor cells
  • bone marrow stromal cells
  • bone healing and regeneration
  • tissue engineering
  • regenerative medicine
  • cells mobilization
  • intra-operative approaches
  • clinical use ethics/regulations burdens

Published Papers (3 papers)

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Research

25 pages, 5947 KiB  
Article
Mesenchymal Stem Cell Therapy for Bone Repair of Human Hip Osteonecrosis with Bilateral Match-Control Evaluation: Impact of Tissue Source, Cell Count, Disease Stage, and Volume Size on 908 Hips
by Philippe Hernigou, Yasuhiro Homma, Jacques Hernigou, Charles Henri Flouzat Lachaniette, Helène Rouard and Sophie Verrier
Cells 2024, 13(9), 776; https://doi.org/10.3390/cells13090776 - 1 May 2024
Viewed by 518
Abstract
We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell therapies. This research emphasizes bone repair according [...] Read more.
We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell therapies. This research emphasizes bone repair according to pre-treatment conditions and the specificities of cell therapy in osteonecrosis repair, indicating a potential for improved bone repair strategies in hips without femoral head collapse. This study utilized a single-center retrospective analysis to investigate the efficacy of cellular approaches in the bone repair of osteonecrosis. It examined the impact on bone repair of tissue source (autologous bone marrow concentrate, allogeneic expanded, autologous expanded), cell quantity (from none in core decompression alone to millions in cell therapy), and osteonecrosis stage and volume. Excluding hips with femoral head collapse, it focused on patients who had bilateral hip osteonecrosis, both pre-operative and post-operative MRIs, and a follow-up of over five years. The analysis divided these patients into seven groups based on match control treatment variations in bilateral hip osteonecrosis, primarily investigating the outcomes between core decompression, washing effect, and different tissue sources of MSCs. Younger patients (<30 years) demonstrated significantly better repair volumes, particularly in stage II lesions, than older counterparts. Additionally, bone repair volume increased with the number of implanted MSCs up to 1,000,000, beyond which no additional benefits were observed. No significant difference was observed in repair outcomes between different sources of MSCs (BMAC, allogenic, or expanded cells). The study also highlighted that a ‘washing effect’ was beneficial, particularly for larger-volume osteonecrosis when combined with core decompression. Partial bone repair was the more frequent event observed, while total bone repair of osteonecrosis was rare. The volume and stage of osteonecrosis, alongside the number of injected cells, significantly affected treatment outcomes. In summary, this study provides comprehensive insights into the effectiveness and variables influencing the use of mesenchymal stem cells in treating human hip osteonecrosis. It emphasizes the potential of cell therapy while acknowledging the complexity and variability of results based on factors such as age, cell count, and disease stage. Full article
(This article belongs to the Special Issue Stem and Progenitor Cells in Bone Regeneration)
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19 pages, 2165 KiB  
Article
In Vitro Mineralisation of Tissue-Engineered Cartilage Reduces Endothelial Cell Migration, Proliferation and Tube Formation
by Encheng Ji, Lieke Leijsten, Janneke Witte-Bouma, Adelin Rouchon, Nunzia Di Maggio, Andrea Banfi, Gerjo J. V. M. van Osch, Eric Farrell and Andrea Lolli
Cells 2023, 12(8), 1202; https://doi.org/10.3390/cells12081202 - 20 Apr 2023
Viewed by 1542
Abstract
Tissue engineering bone via endochondral ossification requires the generation of a cartilage template which undergoes vascularisation and remodelling. While this is a promising route for bone repair, achieving effective cartilage vascularisation remains a challenge. Here, we investigated how mineralisation of tissue-engineered cartilage affects [...] Read more.
Tissue engineering bone via endochondral ossification requires the generation of a cartilage template which undergoes vascularisation and remodelling. While this is a promising route for bone repair, achieving effective cartilage vascularisation remains a challenge. Here, we investigated how mineralisation of tissue-engineered cartilage affects its pro-angiogenic potential. To generate in vitro mineralised cartilage, human mesenchymal stromal cell (hMSC)-derived chondrogenic pellets were treated with β-glycerophosphate (BGP). After optimising this approach, we characterised the changes in matrix components and pro-angiogenic factors by gene expression analysis, histology and ELISA. Human umbilical vein endothelial cells (HUVECs) were exposed to pellet-derived conditioned media, and migration, proliferation and tube formation were assessed. We established a reliable strategy to induce in vitro cartilage mineralisation, whereby hMSC pellets are chondrogenically primed with TGF-β for 2 weeks and BGP is added from week 2 of culture. Cartilage mineralisation determines loss of glycosaminoglycans, reduced expression but not protein abundance of collagen II and X, and decreased VEGFA production. Finally, the conditioned medium from mineralised pellets showed a reduced ability to stimulate endothelial cell migration, proliferation and tube formation. The pro-angiogenic potential of transient cartilage is thus stage-dependent, and this aspect must be carefully considered in the design of bone tissue engineering strategies. Full article
(This article belongs to the Special Issue Stem and Progenitor Cells in Bone Regeneration)
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20 pages, 6034 KiB  
Article
An Intracellular Metabolic Signature as a Potential Donor-Independent Marker of the Osteogenic Differentiation of Adipose Tissue Mesenchymal Stem Cells
by Daniela S. C. Bispo, Catarina S. H. Jesus, Katarzyna Romek, Inês M. C. Marques, Mariana B. Oliveira, João F. Mano and Ana M. Gil
Cells 2022, 11(23), 3745; https://doi.org/10.3390/cells11233745 - 23 Nov 2022
Viewed by 1353
Abstract
This paper describes an untargeted NMR metabolomics study to identify potential intracellular donor-dependent and donor-independent metabolic markers of proliferation and osteogenic differentiation of human adipose mesenchymal stem cells (hAMSCs). The hAMSCs of two donors with distinct proliferating/osteogenic characteristics were fully characterized regarding their [...] Read more.
This paper describes an untargeted NMR metabolomics study to identify potential intracellular donor-dependent and donor-independent metabolic markers of proliferation and osteogenic differentiation of human adipose mesenchymal stem cells (hAMSCs). The hAMSCs of two donors with distinct proliferating/osteogenic characteristics were fully characterized regarding their polar endometabolome during proliferation and osteogenesis. An 18-metabolites signature (including changes in alanine, aspartate, proline, tyrosine, ATP, and ADP, among others) was suggested to be potentially descriptive of cell proliferation, independently of the donor. In addition, a set of 11 metabolites was proposed to compose a possible donor-independent signature of osteogenesis, mostly involving changes in taurine, glutathione, methylguanidine, adenosine, inosine, uridine, and creatine/phosphocreatine, choline/phosphocholine and ethanolamine/phosphocholine ratios. The proposed signatures were validated for a third donor, although they require further validation in a larger donor cohort. We believe that this proof of concept paves the way to exploit metabolic markers to monitor (and potentially predict) cell proliferation and the osteogenic ability of different donors. Full article
(This article belongs to the Special Issue Stem and Progenitor Cells in Bone Regeneration)
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