Administrations of peripheral blood CD34-positive cells contribute to medial collateral ligament healing via vasculogenesis
Abstract
Neoangiogenesis is a key process in the initial phase of ligament healing. Adult human circulating CD34+ cells, an endothelial/hematopoietic progenitor-enriched cell population, have been reported to contribute to neoangiogenesis; however, the therapeutic potential of CD34+ cells for ligament healing is still unclear. Therefore, we performed a series of experiments to test our hypothesis that ligament healing is supported by CD34+ cells via vasculogenesis. Granulocyte colony-stimulating factor-mobilized peripheral blood (GM-PB) CD34+ cells with atelocollagen (CD34+ group), GM-PB mononuclear cells (MNCs) with atelocollagen (MNC group), or atelocollagen alone (control group) was locally transplanted after the creation of medial collateral ligament injury in immunodeficient rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical staining at the injury site demonstrated that molecular and histological expression of human-specific markers for endothelial cells was higher in the CD34+ group compared with the other groups at week 1. Endogenous effect, assessed by capillary density and mRNA expression of vascular endothelial growth factor, was significantly higher in CD34+ cell group than the other groups. In addition to the observation that, as assessed by real-time RT-PCR, gene expression of ligament-specific marker was significantly higher in the CD34+ group than in the other groups, ligament healing assessed by macroscopic, histological, and biomech…
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Preclinical studies regarding MSC-based approaches in MCL injuries have shown promising results.
“Some preclinical studies regarding MSC-based approaches in MCL injuries have shown promising results.”
From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [61]
In immunodeficient rats with MCL injury, transplantation of human peripheral blood CD34+ cells resulted in higher expression of endothelial markers, increased neovascularization, and higher VEGF mRNA than in MNC and control groups.
“The results revealed that the CD34+ group had a higher expression of human-specific markers for endothelial cells, such as Ulex europaeus lectin type 1 (UEA-1), increased neovascularization, and mRNA expression of vascular endothelial growth factor (VEGF), as well as higher gene expression of ligament-specific markers, than the other groups.”
From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [61]
Transplantation of circulating CD34+ cells promotes MCL healing by creating a favorable environment through neovascularization/angiogenesis.
“These findings suggest that transplantation of circulating CD34+ cells promotes MCL healing by creating a favorable environment through neovascularization/angiogenesis.”
From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [61]
In immunodeficient rats with MCL injury, histological and biomechanical properties of early healing MCL were improved in the CD34+ group compared with other groups.
“Furthermore, the histological and biomechanical properties of the early healing MCL were improved compared with those of the other groups.”
From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [61]
In immunodeficient rats with MCL injury, failure load at week 2 was significantly higher in the CD34+ group than in the other groups.
“Biomechanical evaluation by failure load at week 2 was significantly higher in the CD34+ group than in the other groups (CD34+, 6734.766 ± 618.357; MNC, 3530.606 ± 1385.589; control, 3823.325 ± 95.538 mN; p < 0.05, CD34+ vs. MNC and hCD34 vs. control).”
From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [61]
In immunodeficient rats with MCL injury, the number of UEA-1+/HLA-ABC+ cells was significantly higher in the CD34+ group than in both the MNC and control groups.
“The number of UEA-1+/HLA-ABC+ cells was significantly higher in the CD34+ group than in both the mononuclear cell (MNC) and control groups (CD34+, 119.5 ± 20.0; MNC, 54.0 ± 16.5; control, 0.0 ± 0.0 per mm2; p < 0.01, CD34+ vs. control; p < 0.05, CD34+ vs. MNC and MNC vs. control).”
From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [61]
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- Authors
- Tei, K., Matsumoto, T., Mifune, Y., Ishida, K., Sasaki, K., Shoji, T., Kubo, S., Kawamoto, A., Asahara, T., Kurosaka, M., & Kuroda, R.
- Affiliations
- Kobe University (JP)
- RIKEN (JP)
- Tokai University (JP)
- Corresponding author
- Kuroda, Ryosuke
- ORCID
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-01-10
- Volume
- 26
- Issue
- 3
- Pages
- 819-830
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2046662923
- Cited by
- 78
- References
- 58
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 8 · 2012: 9
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- CD34+ cells, peripheral blood stem cells, vasculogenesis, neoangiogenesis, cell transplantation, granulocyte colony-stimulating factor mobilization, vascular endothelial growth factor, capillary density, ligament biomechanics, ligament injury, endothelial cells
- MeSH terms
- Adult, Animals, Cell Differentiation, Female, Hematopoietic Stem Cells, Humans, Inflammation, Leukocytes, Mononuclear, Phenotype, Rats, Nude, Wound Healing, Granulocyte Colony-Stimulating Factor, Collateral Ligaments, Hematopoietic Stem Cell Transplantation, Neovascularization, Physiologic, Antigens, CD34, Hematopoietic Stem Cell Mobilization, Angiogenesis Inhibitors, Rats, Cell- and Tissue-Based Therapy
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