| RESEARCH HIGHLIGHTS |


The in vivo evaluation of this class of clusters provides insights into the toxicity of such compounds, which should help to reduce the stigma associated with heavy-metal toxicity.”


The team intends to improve the biocom-


patibility of the clusters and also functionalize the clusters with certain ligands to enable targeted imaging.


1. Lam, Z., Balasundaram, G., Kong, K. V., Chor, B. Y., Goh, D. et al. High nuclearity carbonyl clusters as near-IR contrast agents for photoacoustic in vivo imaging. Journal of Materials Chemistry B 4, 3886–3891 (2016).


Metabolic disorders:


A STEP CLOSER TO STEM CELL TREATMENTS


A TECHNIQUE THAT GENERATES BROWN FAT CELLS FROM HUMAN BONE MARROW-DERIVED STEM CELLS COULD TRANSFORM THE TREATMENT OF METABOLIC DISORDERS


The differentiation of lymphatic stem cells into fat cells (in green) is promoted by the large amount of extracellular matrix (collagen IV in red) obtained in presence of macromolecular crowding.


A renewable source of brown fat cells, and a simple method for generating them in cell cultures, has been discovered by A*STAR researchers and could help with the development of personalized therapies for metabolic diseases. There are two main types of fat cells, or adi-


pocytes, in the body: white adipocytes that store energy and brown adipocytes that burn energy and generate heat. Babies have an abundance of brown adipocytes as they help infants to keep warm, but recently scientists have discovered the cells also exist in small quantities in adults. By encouraging the body to use, rather than store, excess energy, brown adipocytes could prove useful in the engineered modulation of energy consumption and the regulation of blood sugar levels — two mechanisms that can fail in metabolic disorders such as obesity and diabetes. Until now, there had been no safe, reliable


method of generating large quantities of brown adipocytes to explore their therapeutic potential. A new technique, developed by Michael Raghunath, Cedric Badowski and co-workers at the A*STAR Institute of Medical Biology


www.astar-research.com


together with scientists at the National Uni- versity of Singapore, hinges on unlocking the potential of mesenchymal stem cells taken from human bone marrow (bmMSCs) to differentiate into brown adipocytes.


“WE WANTED TO DETERMINE WHICH FAT CELLS WERE PRESENT IN ADULT BONE MARROW, BECAUSE THIS HADN’T BEEN FULLY INVESTIGATED BEFORE. ”


“We wanted to determine which fat cells


were present in adult bone marrow, because this hadn’t been fully investigated before,” explains Michelle Lee, a researcher on the project. “To our surprise, we found brown adipocytes present, and discovered that the bone marrow environment could trigger bmMSC differentia- tion into brown fat cells. We decided to emulate that environment in the laboratory.” When stem cells are taken out of the body


and placed in cultures, they lose the crowded, intricate microenvironment that enables them to generate a protective extracellular matrix and


function correctly. The team used a technique called ‘macromolecular crowding’ to mimic the microenvironment and encourage bmMSC differentiation. By adding extra molecules to bulk out the culture, Lee explains, there is an increase in reaction mechanisms within the culture that allows the cells to secrete and remodel the extracellular matrix. Using cutting-edge microscopes to visualize


the processes, the researchers found that macromolecular crowding created a cocoon of collagen around the stem cells, greatly enhancing matrix signaling and stimulating large quantities of viable, fully functional brown adipocytes from bmMSCs (see image). “Once the potential for this technology is


fully explored, we could transform the treatment of metabolic disorders and provide considerable benefits for society,“ says Badowski.


1. Lee, M. H., Goralczyk, A. G., Kriszt, R., Ang, X. M., Badowski, C. et al. ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs. Scientific Reports 6, 21173 (2016).


A*STAR RESEARCH 33


© 2016 A*STAR Institute of Medical Biology


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