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Tendons connect muscle to bone and are essential to our body’s ability to stand, run, sit, jump and otherwise haul our skeletons around.

The number of tendon injuries is increasing, impacting athletes and non-athletes alike, and tendon healing is poor and associated with dysfunctional scar tissue.

“By applying the right combination of biochemical factors and mechanical stretches, we think we can differentiate these stem cells toward tendon,” Schiele said. “But we don’t really understand how it’s happening, or how these mechanical forces influence cell behavior, so we’re really trying to get at the processes behind that.” Nate Schiele, Assistant Professor, Biological Engineering

Research over the past 30 years has focused on developing engineered tissue replacements and regenerative therapies using stem cells. But limited understanding of the fundamental biology behind these fibrous cords, including how they develop, and the factors that regulate stem cells to become tendon tissue, referred to as tenogenic differentiation, continue to challenge the advancement of this research.

One of first tendon specific protein markers to identify a tendon cell was discovered in 2001 and progress has been made since then, but there are still many unanswered questions.

Current research in the U of I Department of Biological Engineering in assistant professor Nathan Schiele’s lab aims to understand the mechanisms that guide tendon tissue formation and tenogenic stem cell differentiation to ultimately engineer tendon tissue replacements and regenerative therapies. His lab is one of the few in the country focused on tendon tissue engineering. Research began at U of I in 2015 and is ongoing.

Undergraduate and graduate students in Schiele’s lab work collaboratively, investigating tendon from a biochemical, cellular and mechanical standpoint to understand the factors that regulate tenogenic stem cell differentiation and tendon formation.

The lab brings together students from all levels, funded through many different resources, including the National Institutes of Health (NIH), Idaho IDeA Network of Biomedical Research Excellence (INBRE), Burroughs Wellcome Fund, Beckman Scholars Program, U of I Office of Undergraduate Research and scholar programs across the U of I College of Engineering.

There are more than 16 million reported tendon injuries in the U.S. each year.

Because tendons undergo repetitive motions and sustain such large mechanical loads, they’re prone to injury, said Schiele. Once injured, treatment may involve suturing the tendon through surgery, followed by rehabilitative therapy. Re-rupture is a common occurrence, and patients rarely regain the mechanical strength they once had.

For Schiele, that prognosis is daunting. “I like to hike and ski and bike, so it’s partially selfish to work on tendons because they’re so crucial to an active lifestyle,” Schiele said. “I want to keep doing these activities, even as I get older, so having an alternative treatment option besides sutures seems like a good idea to me.”

The main focus of his research is to better understand the mechanisms that guide tendon tissue formation and tenogenic stem cell differentiation to ultimately engineer tendon tissue replacements and regenerative therapies.

One of the challenges with stem cells, Schiele said, is that once they’re harvested from a person’s bone marrow or fat tissue and injected into the injury site for regeneration, they may remain undifferentiated. This means that the cells, which have the potential to replicate various cell types in the body, can differentiate down any number of lineage tracks — bone, cartilage, muscle, fat or tendon, posing great risk to the patient. Therefore, strategies are needed to induce differentiation of stem cells toward tendon, prior to use in a regenerative tendon therapy.

Schiele and his student research team are trying to ensure proper differentiation of functional tendon tissue in the lab. Such a discovery could eventually allow doctors the ability to extract stem cells from a patient, differentiate them toward tendon cells in the lab, place them on an engineered tissue scaffold that mimics the mechanical strength of tendon, and suture them back into the patient.

“For people who have had major trauma, like an Achilles tendon rupture, we aim to replace or augment that injured tissue with a mechanically functional tendon replacement with cells that act like tendon cells,” Schiele said.

A number of factors exist that may ultimately push a stem cell toward a desired lineage — the shape of the cell, the stiffness of the structure that the cell is placed in, the biochemical environment and growth factors the cell is exposed to, and the mechanical forces, such as stretching, that it undergoes.

It’s these last two factors that Schiele’s research team is honing in on.

“By applying the right combination of biochemical factors and mechanical stretches, we think we can differentiate these stem cells toward tendon,” Schiele said. “But we don’t really understand how it’s happening, or how these mechanical forces influence cell behavior, so we’re really trying to get at the processes behind that.”

Tendon Team

Article by Kate Keenan
Article updated by Alexiss Turner, College of Engineering

Updated Jan. 2020