Scientists find key cues to regulate bone-building cells

February 2, 2017 by Terry Devitt, University of Wisconsin-Madison
Micrographs show the difference between treated and untreated bone cells in a mouse model of severe bone loss. Wisconsin researchers have identified two native protein factors that help keep mesenchymal stem cells -- the master cells that make bone and cartilage -- happy in the laboratory dish. The work could one day help make regenerating lost bone in patients a reality. Credit: Wan-Ju Li

The prospect of regenerating bone lost to cancer or trauma is a step closer to the clinic as University of Wisconsin-Madison scientists have identified two proteins found in bone marrow as key regulators of the master cells responsible for making new bone.

In a study published online today (Feb. 2, 2017) in the journal Stem Cell Reports, a team of UW-Madison scientists reports that the proteins govern the activity of mesenchymal stem cells—precursor cells found in marrow that make bone and cartilage. The discovery opens the door to devising implants seeded with cells that can replace bone tissue lost to disease or injury.

"These are pretty interesting molecules," explains Wan-Ju Li, a UW-Madison professor of orthopedics and biomedical engineering, of the proteins lipocalin-2 and prolactin. "We found that they are critical in regulating the fate of mesenchymal stem cells."

Li and Tsung-Lin Tsai, a UW-Madison postdoctoral researcher, scoured donated human bone marrow using high-throughput protein arrays to identify proteins of interest and then determined the activity of mesenchymal stem cells exposed to the proteins in culture. A goal of the study, says Li, is to better understand the bone marrow niche where mesenchymal stem cells reside in the body so that researchers can improve culture conditions for growing the cells in the lab and for therapy.

The Wisconsin researchers found that exposing mesenchymal stem cells to a combination of lipocalin-2 and prolactin in culture reduces and slows senescence, the natural process that robs cells of their power to divide and grow. Li says keeping the cells happy and primed outside the body, but reining in their power to grow and make until after they are implanted in a patient, is key.

The ability to precisely manipulate mesenchymal stem cells in the laboratory dish and keep them poised to divide and form bone on cue helps pave the way for using cell-bearing three-dimensional matrices to reconstruct large swaths of bone lost to tumors or major trauma. Because bone has some natural healing properties, things like breaks and fractures can often mend themselves. But when large pieces of bone are lost, clinical intervention is required.

"We're seeking better treatments for ," says Li, who is affiliated with the UW School of Medicine and Public Health.

To engineer the growth of new bone in the body through regenerative medicine first requires generating large amounts of good quality cells in the lab, notes Li. In the body are rare. But if cell growth, differentiation and quality can be controlled in the lab dish, it may be possible to create stocks of cells for therapeutic applications and prime them for once implanted in a patient.

The Wisconsin team successfully tested human cells treated with lipocalin-2 and prolactin to regrow bone by implanting them in mice with a calvarial defect, where part of the skullcap has been surgically removed to model critical-sized bone loss.

The human marrow used in the new Wisconsin study was donated by patients undergoing hip replacement surgery. Thus, a caveat to the study is that the protein factors identified by Li and his colleague came from donors with osteoarthritis. However, Li expressed confidence that the factors from the marrow used in the study would be similar or identical to what occurs in a healthy patient.

The new study, says Li, demonstrates a key improvement to the lab culture environment, which seeks to mimic the marrow niche where are found in the body.

Explore further: Researchers take step toward understanding how multiple myeloma takes hold

Related Stories

Researchers take step toward understanding how multiple myeloma takes hold

October 3, 2016
Israeli scientists are moving closer to understanding how multiple myeloma takes hold in bone marrow by identifying what they believe are the mechanisms used by cancer cells to take over. In particular, they have found that ...

Bone marrow inflammation predicts leukemia risk

October 3, 2016
Cancer is generally thought to arise from genetic damage within individual cells, but recent evidence has suggested that abnormal signaling in the surrounding tissue also plays an important role. In a study published September ...

Therapy using stem cells, bone marrow cells, appears safe for patients with ischemic cardiomyopathy

November 18, 2013
Alan W. Heldman, M.D., of the University of Miami Miller School of Medicine, and colleagues conducted a study to examine the safety of transendocardial stem cell injection (TESI) with autologous mesenchymal stem cells and ...

Recommended for you

Forces from fluid in the developing lung play an essential role in organ development

January 23, 2018
It is a marvel of nature: during gestation, multiple tissue types cooperate in building the elegantly functional structures of organs, from the brain's folds to the heart's multiple chambers. A recent study by Princeton researchers ...

Anemia discovery offers new targets to treat fatigue in millions

January 22, 2018
A new discovery from the University of Virginia School of Medicine has revealed an unknown clockwork mechanism within the body that controls the creation of oxygen-carrying red blood cells. The finding sheds light on iron-restricted ...

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.