ArticleProceedings of the National Academy of Sciences of the United States of America2015
PDGFB-based stem cell gene therapy increases bone strength in the mouse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 88 citations in OpenAlex.
- GPNMBCell reports. Medicine · 2026Article
- Spatiotemporal single-cell atlas of suture stem cell dynamics in craniosynostosis.Stem cell research & therapy · 2026Article
- Surface marker-defined functional subpopulations of mesenchymal stromal cells: mechanisms, applications, and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Platelet-derived growth factor-BB (PDGF-BB): pathophysiological roles and therapeutic implications in aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- Osteocytes: master orchestrators of skeletal homeostasis, remodeling, and osteoporosis pathogenesis.Frontiers in cell and developmental biology · 2025Review
- PDGF-BB overexpressing dental pulp stem cells improve angiogenesis in dental pulp regeneration.Frontiers in bioengineering and biotechnology · 2025Article
- Machine Learning-Driven Biomarker Discovery for Skeletal Complications in Type 1 Gaucher Disease Patients.International journal of molecular sciences · 2024Article
- Preosteoclast plays a pathogenic role in syndesmophyte formation of ankylosing spondylitis through the secreted PDGFB - GRB2/ERK/RUNX2 pathway.Arthritis research & therapy · 2023Article
- The efficiency of genetically modified mesenchymal stromal cells combined with a functionally graded scaffold for bone regeneration in corticosteroid-induced osteonecrosis of the femoral head in rabbits.Journal of biomedical materials research. Part A · 2023Article
- Mesenchymal stromal cells, metabolism, and mitochondrial transfer in bone marrow normal and malignant hematopoiesis.Frontiers in cell and developmental biology · 2023Review
- Cellular microenvironment: a key for tuning mesenchymal stem cell senescence.Frontiers in cell and developmental biology · 2023Review
- Single-cell spatiotemporal analysis reveals cell fates and functions of transplanted mesenchymal stromal cells during bone repair.Stem cell reports · 2022Article
- Identification of combined biomarkers for predicting the risk of osteoporosis using machine learning.Aging · 2022Article
- Spatial Organization of Osteoclastic Coupling Factors and Their Receptors at Human Bone Remodeling Sites.Frontiers in molecular biosciences · 2022Article
- Stem cells immortalized by hTERT perform differently from those immortalized by SV40LT in proliferation, differentiation, and reconstruction of matrix microenvironment.Acta biomaterialia · 2021Article
- Skeletal stem cell fate defects caused by Pdgfrb activating mutation.Development (Cambridge, England) · 2021Article
- Effect on Osteogenic Differentiation of Genetically Modified IL4 or PDGF-BB Over-Expressing and IL4-PDGF-BB Co-Over-Expressing Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro.Bioengineering (Basel, Switzerland) · 2021Article
- The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits.Stem cell research & therapy · 2021Article
- PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration.Stem cell research & therapy · 2021Article
- Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis.Cell proliferation · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substantial advances have been made in the past two decades in the management of osteoporosis. However, none of the current medications can eliminate the risk of fracture and rejuvenate the skeleton. To this end, we recently reported that transplantation of hematopoietic stem/progenitor cells (HSCs) or Sca1(+) cells engineered to overexpress FGF2 results in a significant increase in lamellar bone matrix formation at the endosteum; but this increase was attended by the development of secondary hyperparathyroidism and severe osteomalacia. Here we switch the therapeutic gene to PDGFB, another potent mitogen for mesenchymal stem cells (MSCs) but potentially safer than FGF2. We found that modest overexpression of PDGFB using a relatively weak phosphoglycerate kinase (PGK) promoter completely avoided osteomalacia and secondary hyperparathyroidism, and simultaneously increased trabecular bone formation and trabecular connectivity, and decreased cortical porosity. These effects led to a 45% increase in the bone strength. Transplantation of PGK-PDGFB-transduced Sca1(+) cells increased MSC proliferation, raising the possibility that PDGF-BB enhances expansion of MSC in the vicinity of the hematopoietic niche where the osteogenic milieu propels the differentiation of MSCs toward an osteogenic destination. Our therapy should have potential clinical applications for patients undergoing HSC transplantation, who are at high risk for osteoporosis and bone fractures after total body irradiation preconditioning. It could eventually have wider application once the therapy can be applied without the preconditioning.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.