Glucose and Amino Acid Metabolism and Non-invasive Assessment ofHuman Mesenchymal Stem Cell Chondrogenesis in Vitro
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Case Western Reserve University School of Graduate Studies / OhioLINK
2020
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=case159709482941269 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-case1597094829412692021-08-03T07:16:12Z Glucose and Amino Acid Metabolism and Non-invasive Assessment ofHuman Mesenchymal Stem Cell Chondrogenesis in Vitro Zhong, Yi Biomedical Engineering Human Mesenchymal Stem Cells Chondrogenesis Glucose Amino Acids Chondrogenesis of human mesenchymal stem cells (hMSCs) is an important biologicalprocess with applications in cartilage tissue engineering, a promising therapeutic strategyfor the treatment of osteoarthritis. However, the state of the art of cartilage TE still fallsshort of regenerative medicine expectations due to deficiencies in the extracellular matrix(ECM) components such as glycosaminoglycan (GAG) and type II collagen, the majorcomponents responsible for mechanical strength in hyaline cartilage. Further,assessment of construct quality requires tissue sacrifice, preventing longitudinalinvestigation and tissue-specific quality control. The objectives of this study are toinvestigate the uptake/secretion of metabolically important biomolecules: glucose, lactateand amino acids, to investigate culture methods to improve engineered cartilage, and toidentify potential biomarkers for non-invasive monitoring.An aggregate culture system was used as a model of chondrogenesis. Varying initialglucose concentrations led to increased glucose uptake rates and lactate secretion ratesfor aggregates treated with higher initial glucose levels (3 and 4.5 g/l), indicating anincreasing energy requirements from glycolysis during chondrogenesis. In addition, theDNA normalized maximum glucose uptake rate (Vmax) decreased rapidly followed by asteady increase to a plateau. This period of increase coincides with ECM synthesis duringchondrogenesis. These results suggest that culture conditions need to be optimized toprovide increasing amount of glucose. Further, GAG and hydroxyproline (HYP) content of the resultant tissue correlates with the cumulative glucose uptake and lactate secretion,suggesting that either parameter can be used to monitor tissue quality. When themedium-change frequency is doubled, the cumulative glucose uptake increased for allinitial glucose levels leading to significantly improved GAG and HYP content. Further, ourresults showed that cumulative uptake of certain essential amino acids also correlate wellwith DNA normalized GAG and HYP of resultant aggregates.In conclusion, the uptake of glucose and amino acid by hMSCs during chondrogenesiscan be utilized to optimize chondrogenic culture conditions for improved ECM synthesis.Strong correlations between biochemical content of end-point aggregates and cumulativeglucose uptake, lactate secretion, leucine uptake, valine uptake, and tryptophan uptakecan be used to develop non-invasive assessment of hMSCs chondrogenesis in vitro. 2020-09-07 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case159709482941269 http://rave.ohiolink.edu/etdc/view?acc_num=case159709482941269 restricted--full text unavailable until 2022-08-14 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biomedical Engineering Human Mesenchymal Stem Cells Chondrogenesis Glucose Amino Acids |
| spellingShingle |
Biomedical Engineering Human Mesenchymal Stem Cells Chondrogenesis Glucose Amino Acids Zhong, Yi Glucose and Amino Acid Metabolism and Non-invasive Assessment ofHuman Mesenchymal Stem Cell Chondrogenesis in Vitro |
| author |
Zhong, Yi |
| author_facet |
Zhong, Yi |
| author_sort |
Zhong, Yi |
| title |
Glucose and Amino Acid Metabolism and Non-invasive Assessment ofHuman Mesenchymal Stem Cell Chondrogenesis in Vitro |
| title_short |
Glucose and Amino Acid Metabolism and Non-invasive Assessment ofHuman Mesenchymal Stem Cell Chondrogenesis in Vitro |
| title_full |
Glucose and Amino Acid Metabolism and Non-invasive Assessment ofHuman Mesenchymal Stem Cell Chondrogenesis in Vitro |
| title_fullStr |
Glucose and Amino Acid Metabolism and Non-invasive Assessment ofHuman Mesenchymal Stem Cell Chondrogenesis in Vitro |
| title_full_unstemmed |
Glucose and Amino Acid Metabolism and Non-invasive Assessment ofHuman Mesenchymal Stem Cell Chondrogenesis in Vitro |
| title_sort |
glucose and amino acid metabolism and non-invasive assessment ofhuman mesenchymal stem cell chondrogenesis in vitro |
| publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK |
| publishDate |
2020 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=case159709482941269 |
| work_keys_str_mv |
AT zhongyi glucoseandaminoacidmetabolismandnoninvasiveassessmentofhumanmesenchymalstemcellchondrogenesisinvitro |
| _version_ |
1719457877671804928 |