August 9, 2016

Stem cells grown on scaffold mimic hip joint cartilage

At a Glance

  • Adult fat-derived stem cells grown on a 3-D scaffold that mimicked a hip joint surface formed cartilage and maintained the correct shape.
  • The cells were induced to make high levels of an anti-inflammatory protein on demand that prevents joint degradation.
  • The findings could lead to new approaches to treat joint surfaces damaged by osteoarthritis or injury.
3-D woven scaffold Top: Electron microscope image provides a close-up view of the 3-D woven scaffold. Bottom: The scaffold was shaped over a mold, attached to mesh, and seeded with stem cells. After 38 days in culture, the cells had grown to create a smooth, glistening surface. Guikak lab, Washington University

A layer of smooth cartilage lines the ends of the bones in many joints in the body. The cartilage has special properties that enable it to absorb energy, bear weight, and lubricate the joints so they can function seamlessly. In osteoarthritis, this cartilage breaks and wears away. Bones under the cartilage may then rub together, causing pain, swelling, stiffness, and disability.

Osteoarthritis affects more than 27 million Americans age 25 and older, making it the most common type of arthritis. It typically affects the knees, hips, lower back, neck, and hands. Treatments include exercise, medications to control pain, and surgery to reposition or resurface the joint or to replace it with an artificial one. Restoring the cartilage in these joints would be an important advance in the treatment of osteoarthritis.

A team led by Dr. Farshid Guilak, formerly of Duke University and now at Washington University School of Medicine in St. Louis, previously engineered a scaffold to guide stem cells into cartilage-producing cells. The group set out to build on this work by incorporating a gene transfer approach to induce cells to produce an anti-inflammatory compound to prevent further joint degradation. The research was supported in part by NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Results were published on August 2, 2016, in Proceedings of the National Academy of Sciences.

The scientists formed 3-D woven textile scaffolds from a biomaterial approved by the U.S. Food and Drug Administration. The 22-mm scaffolds were shaped over a mold to mimic a hip joint surface and attached to a nylon mesh to maintain their shape. The mechanical properties of the scaffolds could be altered by varying the weave architecture.

Confocal image of live cells embedded in woven scaffold.Stem cells (stained green) grew throughout the pores of the scaffold (stained red).Guikak lab, Washington University

Adult human fat-derived stem cells obtained from liposuction waste were seeded onto the outer surface of the porous scaffolds. The cells and scaffolds were maintained in tissue culture for 38 days. During this time, the cells grew to evenly cover the scaffolds. They produced a matrix made up of proteins, such as collagens, that are key components of joint cartilage. The matrix created a smooth, glistening appearance over the scaffolds.

The scientists next engineered a harmless virus to contain a gene with instructions to make the anti-inflammatory molecule IL-1 receptor antagonist (IL-1Ra). They attached this viral vector to the scaffolds and then added the stem cells, which attached and grew. When they added a chemical to the culture media to turn on the gene, the cells produced high levels of IL-1Ra. When inflammatory molecules were added to the cultures, the IL-1Ra prevented the production of a joint-damaging protein.

The researchers are now refining the system components and testing customized implants in animal models. “Our hope is to prevent, or at least delay, a standard metal and plastic prosthetic joint replacement,” Guilak says.

—by Carol Torgan, Ph.D.

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Reference: Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing. Moutos FT, Glass KA, Compton SA, Ross AK, Gersbach CA, Guilak F, Estes BT. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4513-22. doi: 10.1073/pnas.1601639113. Epub 2016 Jul 18. PMID: 27432980.

Funding: NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Collaborative Research Center; AO Foundation (Davos, Switzerland); Arthritis Foundation; National Science Foundation; and Nancy Taylor Foundation for Chronic Diseases.