Tracking stem cells using tricks learned in outer space

Stem cell science is set to get a boost from an unlikely source: outer space. It turns out that techniques devised to help telescopes peer through the blur of the earth's atmosphere could help scientists peak more deeply into tissues. If the technique, called adaptive optics or AO, works it might prove useful for scientists hoping to track the whereabouts of transplanted stem cells.

A group of researchers at the University of California, Santa Cruz, including CIRM grantee Joel Kubby, have formed the W. M. Keck Center for Adaptive Optical Microscopy, which will apply AO techniques to microscopes built for peering deep into tissues.

A press release from UCSC describes the project:

Principal investigator Joel Kubby, an associate professor of electrical engineering in the Baskin School of Engineering at UCSC, has worked on adaptive optics (AO) systems for large telescopes as well as for biological imaging. In astronomy, AO systems correct the blurring of telescope images caused by turbulence in the Earth's atmosphere. In microscopy, blurring is caused by the flowing cytoplasm of living cells.

"We can get beautiful images of cells close to the surface of the tissue, but if you want to go deep you're out of luck because of the degradation of the image. That was the motivation for this project," said co-investigator William Sullivan, professor of molecular, cell, and developmental biology at UC Santa Cruz. "For cell biologists, anything that improves imaging is a big deal, and this has the potential to open up vast areas of cell biology that have been opaque to us."

In stem cell research, for example, an important bottleneck in efforts to develop stem cell therapies has been the inability to follow injected stem cells and monitor their fates below the surface of the tissue. AO microscopy could solve this problem, and the California Institute for Regenerative Medicine (CIRM) has provided support for the work at UCSC, including funding that led to the development of the team's first AO microscope.

Knowing where a stem cell goes once it has been transplanted is critical to developing new therapies. Unless they go to where the damage is and stay there, those cells won't hold any long-term therapeutic benefit. Tracking cells within tissues could point to better ways of transplanting the cells and, eventually, to more effective therapies.

A.A.

Blood Stem Cell Finding Could Yield Practical Results for BMT

A finding by CIRM-funded researchers at the University of California Santa Cruz sounds pretty esoteric, but could be immensely practical for patients facing a grueling Bone Marrow Transplant (BMT).

Hematopoietic, or blood-forming, stem cells really have one preferred home. They tend to stick to their niche in the bone marrow, with relatively few circulating in the blood stream at any one time. That is why BMT has generally required anesthesia to go in and harvest bone marrow to get the stem cells buried within it. Lately, physicians have been trying to bypass this painful step by giving repeated injections of drugs over time to get the stem cells to leave the bone marrow and circulate in the blood stream where they can be harvested much more easily. But so far, this is still not very efficient and requires the multiple injections.

The UCSC team, lead by Camilla Forsberg, found that a rare molecule, Robo4, anchors the stem cells in the marrow. A drug that blocks Robo4 could be a safer and more effective way of getting stem cells out of the marrow and into the blood circulation where they could be harvested.

In a press release from UCSC Forsberg said:

"If we can get specific and efficient inhibition of Robo4, we might be able to mobilize the hematopoietic stem cells to the blood more efficiently. We're already working on that in the second phase of the project."

Another practical gain may come out of the teams work. Unlike most other types of stem cells, hematopoitic stem cells (HSCs) are very difficult to grow in the lab. They want that comfy home in the bone marrow. Knowing the role of Robo4 might let researchers fluff up the couch in those petri dishes and make the blood forming cells feel more at home. Much more could be learned about HSCs, much more quickly, if that became true.

CIRM Funding: Camilla Forsberg (RN1-00540-1)
Cell Stem Cell, January 2011

D.G.