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Dynamic Imaging of Marrow-Resident Granulocytes Interacting with Human Mesenchymal Stem Cells upon Systemic Lipopolysaccharide Challenge.

Myers JT, Barkauskas DS, Huang AY.

Stem Cells Int. 2013;2013:656839.

Department of Pediatrics, Division of Pediatric Hematology/Oncology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-7288, USA.

Abstract

 

Human mesenchymal stem cells (hMSCs) have gained intense research interest due to their immune-modulatory, tissue differentiating, and homing properties to sites of inflammation. Despite evidence demonstrating the biodistribution of infused hMSCs in target organs using static fluorescenceimaging or whole-body imaging techniques, surprisingly little is known about how hMSCs behave dynamically within host tissues on a single-cell level in vivo. Here, we infused fluorescently labeled clinical-grade hMSCs into immune-competent mice in which neutrophils and monocytes express a second fluorescent marker under the lysozyme M (LysM) promoter. Using intravital two-photon microscopy (TPM), we were able for the first time to capture dynamic interactions between hMSCs and LysM(+) granulocytes in the calvarium bone marrow of recipient mice during systemic LPSchallenge in real time. Interestingly, many of the infused hMSCs remained intact despite repeated cellular contacts with host neutrophils. However, we were able to observe the destruction and subsequent phagocytosis of some hMSCs by surrounding granulocytes. Thus, our imaging platform provides opportunities to gain insight into the biology and therapeutic mechanisms of hMSCs in vivo at a single-cell level within live hosts.

 

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Additional Information

 

Neutrophils are the body’s first line of defense against invading pathogens. The bone marrow is charged with producing, maintaining and mobilizing sufficient number of neutrophils during systemic inflammatory insults. How the bone marrow reacts dynamically under inflammatory conditions in short time scales (seconds – minutes) has been difficulty to ascertain on a single cell level in situ. Myers et al. now provides high spatial-temporal resolution details on what this highly dynamic phenomenon looks like in a live mouse bone marrow undergoing systemic inflammation by using intravital two-photon laser scanning microscopy technique. Furthermore, the investigators also provided detailed description of the interaction between bone marrow-resident neutrophils and administered human-derived mesenchymal stem cells (MSCs). The imaging methodology provides a potentially powerful in vivo validation platform for the development of MSC-based, drug-based or cellular-based therapy research, and provides a useful window into investigations involving the biology of hematopoiesis, cancer metastasis and stem cell niche development.

Figure Legend: depicts a snapshot of the mouse calvarium bone marrow showing the intact bone (blue), LysM+ neutrophils (green), blood vessels and sinusoids (purple) and human mesenchymal stem cells (red).

 

Imaris Snapshot