High dose chemotherapy and radiation have been found to impair the hematopoiesis-supportive capacity of bone marrow stroma. We now provide evidence for an important role of chemotherapy-induced alterations in stromal glycosaminoglycans (GAGs) in reduction of the supportive properties of stromal fibroblasts. Exposure to cytarabine resulted in a pronounced increase in hyaluronan, both in the cell/matrix (p<0.03) and supernatant fraction (p<0.05). Gene expression analysis showed a corresponding increase in gene expression of hyaluronan synthase 1, indicating that the increase in hyaluronan is at least partly under genetic control. Functionally, hyaluronan significantly inhibited the proliferation of early megakaryocytic progenitor cells in a dose dependent way (p=0.01). The increase in hyaluronan was confirmed in vivo by showing a >2-fold increase in bone marrow hyaluronan of patients after chemo- and/or radiotherapy as conditioning for an allogeneic stem cell transplantation, indicating physiologically relevance. Furthermore, there was a trend towards a decrease in the amount and sulfation of stromal heparan sulfate proteoglycans upon exposure to cytarabine, resulting in a 40% reduced binding of SDF1-alpha to stromal cells (p<0.05). In conclusion, there is a pronounced effect of cytarabine treatment on the expression of genes involved in GAG synthesis and degradation, affecting the synthesis and function of stromal GAGs. Our results indicate that chemotherapy-induced changes in stromal GAG profile are likely to affect normal hematopoiesis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.matbio.2007.04.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A light-cured injectable composite hydrogel based on chitosan and decellularized matrix modulates stem cell aggregation behavior for accelerating cartilage defect repair.
Int J Biol Macromol
January 2025
The Affiliated Lihuili Hospital of Ningbo University, Ningbo 315040, China.
Cartilage repair remains a formidable challenge because of its limited regenerative capacity. Construction of a biomimetic hydrogel matrix that can induce cell aggregation is a promising therapeutic option. Cell aggregates are more beneficial than dissociated cells for improving survival and chondrogenic differentiation, thereby facilitating cartilage repair.
View Article and Find Full Text PDFExtracellular vesicles: essential agents in critical bone defect repair and therapeutic enhancement.
Mol Biol Rep
January 2025
Pediatric Cell, and Gene Therapy Research Center Gene, Cell and Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Bone serves as a fundamental structural component in the body, playing pivotal roles in support, protection, mineral supply, and hormonal regulation. However, critical-sized bone injuries have become increasingly prevalent, necessitating extensive medical interventions due to limitations in the body's capacity for self-repair. Traditional approaches, such as autografts, allografts, and xenografts, have yielded unsatisfactory results.
View Article and Find Full Text PDFClinical and Functional Outcomes of Peri-Implant Fractures Associated with Short Proximal Femur Nails: Prevention Strategies and Key Insights.
J Clin Med
January 2025
Discipline of Physiotherapy, Faculty of Health Sciences, European University Miguel de Cervantes, C del Padre Julio Chevalier 2, 47012 Valladolid, Spain.
: Hip fractures are prevalent among the elderly and impose a significant burden on healthcare systems due to the associated high morbidity and costs. The increasing use of intramedullary nails for hip fracture fixation has inadvertently introduced risks; these implants can alter bone elasticity and create stress concentrations, leading to peri-implant fractures. The aim of this study is to investigate the outcomes of peri-implant hip fractures, evaluate the potential causes of such fractures, determine the type of treatment provided, assess the outcomes of said treatments, and establish possible improvement strategies.
View Article and Find Full Text PDFGeneration of Bona Fide Human Induced Trophoblast Stem Cells by Direct Reprogramming of Term Umbilical Cord Cells.
Int J Mol Sci
December 2024
Reproductive Biology Laboratory, Amsterdam University Medical Center Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Placentation disorders, including severe preeclampsia and fetal growth restriction, have their origins in early pregnancy, whereas symptoms typically present later on. To investigate the pathogenesis of these diseases, there is a need for a reliable in vitro model system of early placenta development with known pregnancy outcomes. Therefore, we optimized the generation of human induced trophoblast stem cells (iTSCs) from term umbilical cord, enabling non-invasive collection of patient-derived material immediately after birth.
View Article and Find Full Text PDFThe Role of Bone Marrow Stromal Cell Antigen 2 (BST2) in the Migration of Dendritic Cells to Lymph Nodes.
Int J Mol Sci
December 2024
College of Life Sciences and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
Bone marrow stromal antigen 2 (BST2) is a host-restriction factor that plays multiple roles in the antiviral defense of innate immune responses, including the inhibition of viral particle release from virus-infected cells. BST2 may also be involved in the endothelial adhesion and migration of monocytes, but its importance in the immune system is still unclear. Immune cell adhesion and migration are closely related to the initiation of immune responses.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!