HRMAS 1H-NMR measured changes of the metabolite profile as mesenchymal stem cells differentiate to targeted fat cells in vitro: implications for non-invasive monitoring of stem cell differentiation in vivo

• Type of Material: Article
• Authors: Chunmeng Shi, Emory University; Xiaoxia Wang, Emory University; Shaoxiong Wu, Emory University; Ying Zhu, Emory University; Leland W. K. Chung, Emory University; Hui Mao, Emory University
• Language: English
• Date: 2008-12
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 John Wiley & Sons, Ltd.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/term.120/abstract;jsessionid=8DF112CB4D82B4D3B3806600454E10C6.f04t04
• Title of Journal or Parent Work: Journal of Tissue Engineering and Regenerative Medicine
• ISSN: 1932-6254
• Volume: 2
• Issue: 8
• Start Page: 482
• End Page: 490
• Grant/Funding Information: This work was partially supported (to C.S.) by the NSFC programme (Grant No. 30400188 and 30870966), the ‘973’ programme (Grant No. 2005CB522605), the FANEDD programme (Grant No. 200777) and the PCSIRT program (Grant No. IRT0712) from China, and (to H.M.) by a pilot grant from Emory Alzheimer’s Disease Research Center under the programme project Grant No. P50AG025688) from NIH, USA.
• Keywords: adipogenic differentiation; magnetic resonance; stem cell; imaging; metabolite; spectroscopy
• Research Categories: Health Sciences, General; Health Sciences, Obstetrics and Gynecology; Health Sciences, Radiology

Abstract

Mesenchymal stemcells (MSCs) have shown a great potential for clinical applications in regenerative medicine. However, it remains challenging to follow the transplanted cell grafts in vivo. Nuclear magnetic resonance spectroscopy (NMR or MRS) is capable of determining and quantifying the cellular metabolites in tissue and organs non-invasively, therefore it is an attractive method for monitoring and evaluating the differentiation and functions of transplanted stem cells in vivo. In this study, metabolic changes of MSCs undergoing adipogenic differentiation to targeted fat cells were investigated in vitro, using solid-state high-resolution magic angle spinning 1H nuclear magnetic resonance spectroscopy. Quantification of metabolite concentrations before and after differentiation of MSCs showed decreased levels of intracellular metabolites, including choline, creatine, glutamate and myo-inositol, and a substantially increased level of fatty acids, when mesenchymal stem cells were differentiated preferentially to fat cells. Intracellular creatine, myo-inositol and choline reduced from 10.4 ± 0.72, 16.2 ± 1.2 and 8.22 ± 0.51 mm to 3.27 ± 0.34, 6.1 ± 0.46 and 3.11 ± 0.32 mm, respectively, while fatty acids increased from 32.6 ± 1.5 to 91.2 ± 3.2 mm after undergoing 3 weeks of differentiation. The increase of the fatty acid concentration measured by NMR is confirmed by the observation of 80% fat cells in differentiated cells by cell counting assay, suggesting resonances from fatty acids may be used as metabolite markers for monitoring MSC differentiation to fat cells in vivo, using the magnetic resonance spectroscopic technique readily available on MRI scanners.