Induced Pluripotent Stem Cells Make Cartilage

Induced pluripotent stem cells (iPSCs) are made from adult cells through genetic engineering techniques that drive terminally-differentiated adult cells to revert into embryonic-like cells. iPSCs have the capacity to form any cell type in the adult body, and they may represent the future of regenerative medicine when it comes to treatment of some diseases.

On the 30th of October, 2012, scientists from Durham NC reported that they were able to make cartilage from iPSCs. The cartilage made by iPSCs was not simply the fibrous cartilage found in the ribs and between the connection at the pelvis, but the whitish, hyaline cartilage found at weight-bearing joints. Hyaline cartilage acts as a shock absorber at the hip and knee joints and has proven difficult to make in culture.

According the Farshid Guilak, professor of orthopedics surgery at Duke University Medical Center and senior author of this study: “This technique of creating pluripotent stem cells is a way to take adult cells and convert them so that they have the properties of embryonic stem cells.”

Dr. Guilkak continued, “Adult stem cells are limited in what they can do and embryonic stem cells have ethical issues.” What this research shows in a mouse model is that ability to create an unlimited supply of stem cells that can turn into any type of tissue – in this case cartilage, which has no ability to regenerate itself.

Hyaline cartilage, which is found at articular surfaces (the surfaces between joints, allows us to walk and climb stairs. However, the everyday wear-and-tear or an injury can degrade the cartilage, leaving bones to grind against bones. the result is bone fragmentation, extensive inflammation and pain (osteoarthritis), and the replacement of that joint with an artificial joint. Articular cartilage has a very limited ability to repair itself and damage and osteoarthritis are the leading causes of impairment in older people.

Guilak’s research group, led by postdoctoral research fellow, Brian Diekman, is an alternative to other procedures presently in use, which include the application of stem cells from bone marrow or fat to the damaged cartilage.

The main challenge in using iPSCs was differentiate the cells so that they provided a relatively pure population of cartilage-making cells (chondrocytes). To hone their protocol for making and selecting chondrocytes from iPSCs, Diekman devised a technique that caused only those iPSCs that had differentiated into mature chondrocytes to glow a fluorescent green color. This provided a tag that Diekman and his colleagues used to sort the mature chondrocytes from the other cells.

The isolated chondrocytes made beautiful cartilage that had all the strength and resilience of nature cartilage. As noted by Diekman, “This was a multi-step approach, with the initial differentiation, the sorting, and then proceeding to make the tissue (cartilage in this case). What this shows is that iPSCs can be used to make high quality cartilage, either for replacement tissue or as a way to study disease and potential treatments.”

According to Diekman and Guilak, the next step in this research is to use human iPSCS to test and ultimately refine their cartilage-growing protocol. Guilak summarized his work with these words: “The advantage of this technique is that we can grow a continuous supply of cartilage in a dish. In addition to cell-based therapies, iPSC technology can also provide patient-specific cell and tissue models that could be used to screen for drugs to treat osteoarthritis.”

This work was published in the Proceedings of the National Academy of Sciences USA, 2012, DOI: 10.1073/pnas.1210422109.