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October 28, 2016

Cartilage prepared from iPS cells do not activate immune cells

Scientists at CiRA show that like normal cartilage, cartilage derived from iPS cells can be used to treat cartilage disease without matching the donor and recipient

In most cell transplantations, it is imperative to match the donor and patient to avoid immune responses that reject the transplant. Cartilage is one exception, and several thousand transplantations without such matching are known. The reason for this exception is the nature of cartilage. "Cartilage consists of chondrocytes and extracellular matrix," explains CiRA Professor Noriyuki Tsumaki. Chondrocytes are responsible for secreting extracellular matrix (ECM) proteins. When cartilage is transplanted the ECM protects the chondrocytes from the host's immune cells, thus preventing an immune response. In addition, chondrocytes express limited amounts of HLA on the cell surface, which are responsible for triggering the immune reaction.

However, cartilage transplants are hard to come by. Tsumaki and his team have therefore been seeking other sources for cartilage, focusing on induced pluripotent stem (iPS) cells. While it was expected that cartilage derived from iPS cells should also be immune privileged, the Tsumaki lab reports the first proof in Tissue Engineering Part A.

Like chondrocytes from normal cartilage, the study shows that iPS cell-derived chondrocytes express limited amounts of HLA, and iPS cell-derived cartilage does not stimulate T cells, which are key players in immune reactions that reject the donor tissue. Tsumaki himself is an orthopedic surgeon who aims to translate his research to patient treatment for knee ailments. "This finding will influence our strategy for clinical care," he said. The lab is already at the forefront of creating both chondrocytes and cartilage using iPS cells and has already tested the effects of their transplantation in a number of animals.

Donor matching can be a painstakingly long process, especially if the patient has the misfortune of a rare HLA type. The immuno-privilege of iPS cell-derived cartilage, on the other hand, suggests any healthy donor is sufficient. Tsumaki anticipates this work to expedite the use of iPS cells for cartilage injuries. "I hope to start patient care in the next few years."

Paper Details
  • Journal: Tissue Engineering
  • Title: "Limited immunogenicity of human iPS cell-derived cartilages"
  • Authors: Takeshi Kimura, Akihiro Yamashita, Keiichi Ozono, and Noriyuki Tsumaki

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