An integrated optical platform for micromanipulation of cells and tissue in live animals

Abstract

The hematopoietic stem cell niche is a specialized bone marrow (BM) microenvironment where blood-forming cells reside. Interactions between these rare cells and their niche need to be studied at the single-cell level. While live animal cell tracking with optical microscopy has proven useful for this purpose, a more thorough characterization requires novel approaches. This can be accomplished by using an integrated optical platform for cell and tissue manipulations (cell transplantation and extraction) in the skull bone of live mice. The platform integrates a non-damaging laser ablation microbeam for bone removal and tissue cutting, optical tweezers for single cell trapping, and a video-rate scanning microscope. For single cell delivery, a narrow channel is ablated through bone under imaging guidance. Cells are then transferred from a micropipette into an optical trap, which brings cells into the BM through the channel. The survival and proliferation of implanted cells can be tracked in vivo by imaging. For cell extraction after laser bone thinning, different approaches can be implemented and three of them are presented.