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Signaling in three-dimension

Posted Aug 12 2009 12:00am

As pathologists we tend to "think" spatially in the two-dimensional world of our glass slides but a recent paper in PNAS abstract link (subscription required for full-text) challenged me to go to another dimension.

Rossello et al begin by noting how cells and tissues continuously coordinate spatial relationships via gap junction-mediated cell-to-cell communication.  Such gap junction intercellular communication (GJIC) is necessary both in development and as a part of tissue remodeling and repair.  They hypothesize that genetically engineering cells to overexpress gap junction proteins, in this case connexin 43, should result in enhanced regeneration of larger and more uniform three-dimensional tissue volume.  They use bone as an experimental model.

"In bone marrow stromal cells (BMSC), GJIC and osteogenic differentiation were compromised in 3D cultures relative to 2D monolayers and in the core of 3D cultures relative to the surface. Overexpression of connexin 43 (Cx43) via transduction of BMSCs with a lentivirus overcame this problem, enhancing both the magnitude and spatial distribution of GJIC and osteogenic differentiation markers throughout 3D constructs. Transplantation of cells overexpressing Cx43 resulted in an increased volume fraction and spatial uniformity of bone in vivo, relative to nontransduced BMSCs. Increased GJIC also enhanced the effect of a potent osteoinductive agent (BMP-7), suggesting a synergism between the soluble factor and GJIC."


This is some very cool stuff!  As one interested in lung pathology, I wonder if anyone has looked at this with respect to interstitial lung disease and fibrosis.  I'm off to PubMed!

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