Medicine at Michigan-

Michael Long
Photo: D.C. Goings

When it’s time to make bone, Michael Long knows that stem cells need intimate contact with their own kind. In a study published in the September 2000 issue of Nature Biotechnology, he reported that osteogenic or bone-producing stem cells from human bone marrow merge into three-dimensional spheres to produce bits of crystallized bone. Long is the first scientist to grow small amounts of human bone in culture from an isolated cell population containing osteogenic stem cells.

“Engineering the growth of human bone is a complex process,” says Long. “It requires a precise combination of regulatory signals, growth factors, supporting matrix, cell architecture and density. Everything has to occur in a specific order and timing is critical.”

Most of Long’s research focuses on understanding the cellular and molecular signals involved in producing bone and its connective tissue from osteogenic and other types of stem cells in human bone marrow. Next year he hopes to begin animal testing of a new stem cell therapy for osteoporosis — the progressive, aging-related bone loss that leads to fracture, disability or death for 75 million people worldwide.

Long wants to transfer his research on how stem cells build bone to the private sector. He has started an Ann Arbor-based biotechnology company called Osteomics. The company finds new therapeutic targets for bone diseases and works with biopharmaceutical firms searching for new and more effective treatments for osteoporosis and other bone diseases.

“Current therapies can stop or delay bone loss, but they can’t stimulate new bone growth,” he says. “We focus on therapies that stimulate bone formation. If we could transplant osteogenic stem cells from bone marrow into areas with damaged bone or around a hip implant, it might be possible to induce growth of new bone cells.”

One big problem is finding the right cells to transplant. Four different varieties of stem cells have osteogenic capacity, according to Long. Some become bone and cartilage; some are destined to be blood cells; some develop into connective tissues. Much more research is needed to determine how these various types of stem cells are related and what stage of development would transplant best.

What really intrigues Long these days is a new phenomenon, discovered within the last 18 months, called stem cell plasticity. What if you could harvest stem cells from human bone marrow, which predominantly grow up to become blood cells, and manipulate them to become cardiac, liver or neural cells instead? Recent evidence indicates it’s possible, but the clinical significance remains unclear.

Jennifer Fuller Photo: Martin Vloet

Jennifer Fuller, a graduate student in the Long laboratory, and Theresa Gratsch, a research investigator in Sue O’Shea’s laboratory, recently found one way to make stem cell plasticity work in cultures of bone marrow cells from adult mice.

“We found that exposing cells to powerful embryonic growth factors called noggin and chordin caused them to stop differentiating into bone cells called osteoblasts and become neural cells instead,” Fuller says. “We used to think that only embryonic stem cells had the potential to differentiate into neurons, but now we know that adult stem cells also have this capacity.”

Also:

Unlocking the Secrets of Stem Cells

A Stem Cell Glossary