Citrate-based materials fuel human stem cells by metabonegenic regulation
| Autor: | Xiaochun Bai, Maria R. Hudock, Denghui Xie, Dingying Shan, Xinggui Tian, Jian Yang, Chuying Ma, Jimin P. Kim, Xiang Ao, Qiaoling Lin |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Bone Regeneration Biocompatible Materials 02 engineering and technology Models Biological Citric Acid Rats Sprague-Dawley Phosphoserine 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate Biopolymers Tissue engineering Osteogenesis Cell Adhesion Animals Humans Stem Cell Niche Bone regeneration Cell Proliferation Multidisciplinary Skull Fractures Symporters Tissue Engineering Tissue Scaffolds Cell growth Regeneration (biology) Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells 021001 nanoscience & nanotechnology Biodegradable polymer Rats Cell biology Disease Models Animal Phenotype 030104 developmental biology PNAS Plus chemistry Stem cell 0210 nano-technology Femoral Fractures Metabolic Networks and Pathways |
| Zdroj: | Proceedings of the National Academy of Sciences. 115 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1813000115 |
| Popis: | A comprehensive understanding of the key microenvironmental signals regulating bone regeneration is pivotal for the effective design of bioinspired orthopedic materials. Here, we identified citrate as an osteopromotive factor and revealed its metabonegenic role in mediating citrate metabolism and its downstream effects on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our studies show that extracellular citrate uptake through solute carrier family 13, member 5 (SLC13a5) supports osteogenic differentiation via regulation of energy-producing metabolic pathways, leading to elevated cell energy status that fuels the high metabolic demands of hMSC osteodifferentiation. We next identified citrate and phosphoserine (PSer) as a synergistic pair in polymeric design, exhibiting concerted action not only in metabonegenic potential for orthopedic regeneration but also in facile reactivity in a fluorescent system for materials tracking and imaging. We designed a citrate/phosphoserine-based photoluminescent biodegradable polymer (BPLP-PSer), which was fabricated into BPLP-PSer/hydroxyapatite composite microparticulate scaffolds that demonstrated significant improvements in bone regeneration and tissue response in rat femoral-condyle and cranial-defect models. We believe that the present study may inspire the development of new generations of biomimetic biomaterials that better recapitulate the metabolic microenvironments of stem cells to meet the dynamic needs of cellular growth, differentiation, and maturation for use in tissue engineering. |
| Databáze: | OpenAIRE |
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