Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament
Abstract
We performed this study to investigate the therapeutic role of vascular endothelial growth factor (VEGF) in medial collateral ligament (MCL) healing. Murine muscle derived stem cells (MDSCs) obtained via the preplate technique were retrovirally transduced to express: (1) VEGF and nLacZ (MDSC-VEGF), (2) soluble fms-like tyrosine kinase-1 (sFLT1, a VEGF-specific antagonist) and nLacZ (MDSC-sFLT1), and (3) nLacZ (MDSC-nLacZ). After transecting the MCL of immunodeficient rats, 5 × 10(5) cells of each of the transduction groups list above were transplanted into the MCL injury site. A control group was injected with phosphate-buffered saline (PBS) only. Immunohistochemical staining demonstrated that there were more Isolectin B4 and β-galactosidase double positive cells in the rats transplanted with MDSC-VEGF transduced cells than the other groups at week 1. Capillary density was significantly higher in the MDSC-VEGF group than the other groups at week 2; however, there were no significant differences in the biomechanical assessment between the MDSC-VEGF and MDSC-nLacZ groups. On the other hand, the MDSC-sFLT1 group revealed a lower capillary density than the other two groups and the functional ligament healing of the MDSC-sFLT1 group was significantly decreased compared to the other groups when assessed biomechanically. The findings of the present study suggest that angiogenesis plays a critical role in the healing process of injured MCL.
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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 [62]
Transplantation of MDSCs into the injured MCL could accelerate the functional healing process, and MCL repair after MSC therapy might occur due to paracrine effects derived from the cells involved in angiogenesis.
“These results suggest that the transplantation of MDSCs into the injured MCL could accelerate the functional healing process, and MCL repair after MSC therapy might occur due to paracrine effects derived from the cells involved in angiogenesis.”
From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [62]
In immunodeficient rats with MCL injury, transplantation of MDSCs transduced with the VEGF gene resulted in significantly higher capillary density without significant differences in biomechanical properties compared to other groups.
“Capillary density was significantly higher in the experimental group without significant differences in biomechanical properties compared to the other groups.”
From Mesenchymal Stem Cells for Enhanced Healing of the Medial Collateral Ligament of the Knee Joint (2023) · cites this paper as [62]
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References 45 · Cited by 40
- Authors
- Nishimori, M., Matsumoto, T., Ota, S., Kopf, S., Mifune, Y., Harner, C., Ochi, M., Fu, F. H., & Huard, J.
- Affiliations
- University of Pittsburgh (US)
- Hiroshima University (JP)
- University of Pittsburgh Medical Center (US)
- Corresponding author
- Huard, Johnny
- ORCID
- Venue
- Journal of Orthopaedic Research
- Publisher
- Wiley
- Published
- 2011-09-12
- Volume
- 30
- Issue
- 4
- Pages
- 627-633
- ISSN
- 0736-0266 (ISSN-L)
- 1554-527X
- OpenAlex
- W2002912972
- Cited by
- 40
- References
- 45
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 4 · 2013: 5 · 2012: 4
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Orthopaedic Research® (publishedVersion)
- PubMed (publishedVersion)
- D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Keywords
- angiogenesis, medial collateral ligament injury, muscle-derived stem cells, vascular endothelial growth factor, soluble fms-like tyrosine kinase-1, ligament healing, capillary density, stem cell transplantation, ligament biomechanics, retroviral transduction
- MeSH terms
- Animals, Biomechanical Phenomena, Cells, Cultured, Female, Knee Injuries, Lac Operon, Mice, Inbred C57BL, Rats, Nude, Stem Cells, Wound Healing, Medial Collateral Ligament, Knee, Muscle, Skeletal, Neovascularization, Physiologic, Recovery of Function, Stem Cell Transplantation, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor A, Mice, Rats
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