Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect
Background: A critical size bone defect is a clinical scenario in which bone is lost or excised due to trauma, infection, tumor, or other causes, and cannot completely heal spontaneously. The most common treatment for this condition is autologous bone grafting to the defect site. However, autologous...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
|
| Series: | Journal of Orthopaedic Translation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X2200047X |
| _version_ | 1797989945632096256 |
|---|---|
| author | Elijah Ejun Huang Ning Zhang Edward A. Ganio Huaishuang Shen Xueping Li Masaya Ueno Takeshi Utsunomiya Masahiro Maruyama Qi Gao Ni Su Zhenyu Yao Fan Yang Brice Gaudillière Stuart B. Goodman |
| author_facet | Elijah Ejun Huang Ning Zhang Edward A. Ganio Huaishuang Shen Xueping Li Masaya Ueno Takeshi Utsunomiya Masahiro Maruyama Qi Gao Ni Su Zhenyu Yao Fan Yang Brice Gaudillière Stuart B. Goodman |
| author_sort | Elijah Ejun Huang |
| collection | DOAJ |
| description | Background: A critical size bone defect is a clinical scenario in which bone is lost or excised due to trauma, infection, tumor, or other causes, and cannot completely heal spontaneously. The most common treatment for this condition is autologous bone grafting to the defect site. However, autologous bone graft is often insufficient in quantity or quality for transplantation to these large defects. Recently, tissue engineering methods using mesenchymal stem cells (MSCs) have been proposed as an alternative treatment. However, the underlying biological principles and optimal techniques for tissue regeneration of bone using stem cell therapy have not been completely elucidated. Methods: In this study, we compare the early cellular dynamics of healing between bone graft transplantation and MSC therapy in a murine chronic femoral critical-size bone defect. We employ high-dimensional mass cytometry to provide a comprehensive view of the differences in cell composition, stem cell functionality, and immunomodulatory activity between these two treatment methods one week after transplantation. Results: We reveal distinct cell compositions among tissues from bone defect sites compared with original bone graft, show active recruitment of MSCs to the bone defect sites, and demonstrate the phenotypic diversity of macrophages and T cells in each group that may affect the clinical outcome. Conclusion: Our results provide critical data and future directions on the use of MSCs for treating critical size defects to regenerate bone.Translational Potential of this article: This study showed systematic comparisons of the cellular and immunomodulatory profiles among different interventions to improve the healing of the critical-size bone defect. The results provided potential strategies for designing robust therapeutic interventions for the unmet clinical need of treating critical-size bone defects. |
| first_indexed | 2024-04-11T08:28:40Z |
| format | Article |
| id | doaj.art-1eae0eb5df384bc0963b35da7fbd8efa |
| institution | Directory Open Access Journal |
| issn | 2214-031X |
| language | English |
| last_indexed | 2024-04-11T08:28:40Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Orthopaedic Translation |
| spelling | doaj.art-1eae0eb5df384bc0963b35da7fbd8efa2022-12-22T04:34:37ZengElsevierJournal of Orthopaedic Translation2214-031X2022-09-01366474Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defectElijah Ejun Huang0Ning Zhang1Edward A. Ganio2Huaishuang Shen3Xueping Li4Masaya Ueno5Takeshi Utsunomiya6Masahiro Maruyama7Qi Gao8Ni Su9Zhenyu Yao10Fan Yang11Brice Gaudillière12Stuart B. Goodman13Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USADepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USADepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA; Corresponding author. Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.Background: A critical size bone defect is a clinical scenario in which bone is lost or excised due to trauma, infection, tumor, or other causes, and cannot completely heal spontaneously. The most common treatment for this condition is autologous bone grafting to the defect site. However, autologous bone graft is often insufficient in quantity or quality for transplantation to these large defects. Recently, tissue engineering methods using mesenchymal stem cells (MSCs) have been proposed as an alternative treatment. However, the underlying biological principles and optimal techniques for tissue regeneration of bone using stem cell therapy have not been completely elucidated. Methods: In this study, we compare the early cellular dynamics of healing between bone graft transplantation and MSC therapy in a murine chronic femoral critical-size bone defect. We employ high-dimensional mass cytometry to provide a comprehensive view of the differences in cell composition, stem cell functionality, and immunomodulatory activity between these two treatment methods one week after transplantation. Results: We reveal distinct cell compositions among tissues from bone defect sites compared with original bone graft, show active recruitment of MSCs to the bone defect sites, and demonstrate the phenotypic diversity of macrophages and T cells in each group that may affect the clinical outcome. Conclusion: Our results provide critical data and future directions on the use of MSCs for treating critical size defects to regenerate bone.Translational Potential of this article: This study showed systematic comparisons of the cellular and immunomodulatory profiles among different interventions to improve the healing of the critical-size bone defect. The results provided potential strategies for designing robust therapeutic interventions for the unmet clinical need of treating critical-size bone defects.http://www.sciencedirect.com/science/article/pii/S2214031X2200047XBone graftCritical-size bone defectCyTOFMacrophagesStem cellsT cells |
| spellingShingle | Elijah Ejun Huang Ning Zhang Edward A. Ganio Huaishuang Shen Xueping Li Masaya Ueno Takeshi Utsunomiya Masahiro Maruyama Qi Gao Ni Su Zhenyu Yao Fan Yang Brice Gaudillière Stuart B. Goodman Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect Journal of Orthopaedic Translation Bone graft Critical-size bone defect CyTOF Macrophages Stem cells T cells |
| title | Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect |
| title_full | Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect |
| title_fullStr | Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect |
| title_full_unstemmed | Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect |
| title_short | Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect |
| title_sort | differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect |
| topic | Bone graft Critical-size bone defect CyTOF Macrophages Stem cells T cells |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X2200047X |
| work_keys_str_mv | AT elijahejunhuang differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT ningzhang differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT edwardaganio differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT huaishuangshen differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT xuepingli differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT masayaueno differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT takeshiutsunomiya differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT masahiromaruyama differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT qigao differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT nisu differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT zhenyuyao differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT fanyang differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT bricegaudilliere differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect AT stuartbgoodman differentialdynamicsofbonegrafttransplantationandmesenchymalstemcelltherapyduringbonedefecthealinginamurinecriticalsizedefect |