Cartilage from the skin
Cartilage tissue was obtained from induced pluripotent stem cells
LifeSciencesToday based on materials from Duke University Medical Center:
Duke researchers engineer cartilage from pluripotent stem cellsA team of scientists at Duke University Medical Center has grown cartilage tissue from induced pluripotent stem cells (iPSCs) of a mouse.
The obtained chondrocytes are suitable both for the elimination of cartilage defects and for the study of osteoarthritis. This achievement, confirming that induced pluripotent stem cells are quite suitable for growing articular cartilage from the patient's own tissues, is reported online in the journal Proceedings of the National Academy of Sciences (Diekman et al., Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells).
"The method of producing induced pluripotent stem cells – an achievement for which Shinya Yamanaka from Kyoto University was awarded the Nobel Prize this year – provides for such a transformation of adult stem cells that they acquire the properties of embryonic stem cells," says the head of the study Farshid Gilak, PhD, professor of orthopedic surgery at Duke University.
"Adult stem cells are limited in their capabilities, and the use of embryonic stem cells is associated with ethical issues," continues Professor Gilak. "What the mouse model shows in this study is the ability to create an unlimited number of stem cells that can be transformed into any type of tissue – in this case, into cartilage, which is deprived of the ability to regenerate independently."
Articular cartilage is a shock absorber of joints. It is a fabric that allows you to walk, climb stairs, jump and do your daily work without experiencing pain. But normal wear and tear or injuries reduce its functionality and lead to the development of osteoarthritis. Since articular cartilage is practically incapable of regeneration, damage and osteoarthritis are the leading causes of joint diseases in elderly people, in which doctors and patients often face the need for joint replacement.
A group led by Brian Diekman, PhD, has resorted to the most modern technologies that have made induced pluripotent stem cells a promising alternative to other methods of tissue engineering. These methods are based on the transformation of adult stem cells derived from bone marrow or adipose tissue.
One of the problems that the researchers sought to solve was obtaining an equally differentiated population of chondrocytes – cells that make up cartilage and synthesize collagen – and cutting off other cell types that are capable of forming induced pluripotent stem cells.
To do this, they induced differentiation into iPSCs chondrocytes obtained from adult mouse fibroblasts by treating cultures with a growth medium. In addition, these cells expressed the green fluorescent protein only when they successfully differentiated into chondrocytes. Now the glowing green chondrocytes could be easily identified and sorted from unwanted cells.
Illuminating chondrogenesis: mouse induced pluripotent stem cells in the process of chondrogenesis.
Under the control of a specific promoter of chondrocytes, in addition to type II collagen (red), green fluorescent protein is expressed by F-actin (purple) and nuclei (blue) of differentiated cells.
Scientists used cell sorting to produce tissue-engineered cartilage for potential use in the treatment of cartilage defects and the development of new drugs for the treatment of osteoarthritis.
Photo: Brian Diekman and Johannah Sanchez-Adams
The resulting chondrocytes produced a large number of cartilage components, including collagen, and demonstrated stiffness characteristic of natural cartilage tissue. This means that they will cope well with the task of correcting cartilage defects in the body.
"We used a multi–step approach with initial differentiation, subsequent sorting and transition to tissue creation," says Dr. Dickman. "What we have proven is the possibility of using iPSCs to produce high-quality cartilage suitable both for tissue replacement and for studying diseases and possible methods of their treatment."
At the next stage of the study, the scientists plan to test this method of creating cartilage on human induced pluripotent stem cells.
"The advantage of this method is that we can continuously obtain cartilage in vitro," concludes Professor Gilak. "In addition to cell therapy, the iPSC method makes it possible to create patient-specific cell and tissue models that can be used for screening drugs for the treatment of osteoarthritis, for which there are no cures or effective therapies that can stop cartilage loss today."
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