Cartilage Engineered Using Human Embryonic Stem Cells
18 Sep, 2007 12:13 pm
Rice University researchers have engineered musculoskeletal cartilages with human embryonic stem cells, with the hope of eventually using the neotissue for the replacement of damaged or diseased cartilages in humans.
The need for cartilage replacements results from the inability of human musculoskeletal cartilages to effectively heal. This can lead to functionally deficient tissue and can result in the clinical syndrome known as arthritis, a major clinical problem with significant social and economic burdens.
Though important progress has been made in recent years toward engineering replacement cartilages in the laboratory, there are still many hurdles to overcome, including the identification of a useful source of cells that can generate the new cartilage. Cartilage tissue engineering requires many cells to produce a piece of tissue that has clinically relevant dimensions, and this requirement far exceeds our current capability to obtain cartilage cells from an individual patient.
Stem cells, from both embryonic and adult sources, may address this particular hurdle, though a great deal of work still needs to be performed. Human embryonic stem cells (hESCs), in particular, have been scarcely studied to date for cartilage applications.
Toward understanding the usefulness of hESCs for cartilage engineering, two questions need to be addressed. First, how can the cells be “differentiated” or coaxed into cartilage-producing cells? Second, how can the cells be used in tissue engineering?
In a recent study published in the journal Stem Cells, the Rice University researchers, including myself, Ms. Gwen M.B. Hoben, and Professor Kyriacos A. Athanasiou, used National Institutes of Health (NIH)-approved hESCs which were differentiated in conditions with distinct regimens of biochemical agents (growth factors) that are known to have cartilage-inducing properties. The resulting cells were then used in a tissue engineering strategy called self-assembly, which deviates from traditional approaches in that self-assembly does not require any scaffold material to direct the formation of tissue.
This self-assembly approach with the hESC-derived cartilage cells resulted in uniform pieces of cartilage with cellular, biochemical, and biomechanical properties most similar to the cartilage in the jaw joint (i.e., the temporomandibular joint disc) and the knee meniscus, which are both fibrocartilages. Interestingly, the cartilages from each distinct biochemical regimen had a unique set of characteristics, suggesting that the cartilage-producing ability of the cells can be manipulated.
This study was the first demonstration of the ability of cartilage-differentiated hESCs to “self-assemble” and produce such robust cartilage, though there is still room for improvement. Additionally, it was the first time that a study demonstrated that different types of cartilage could be produced with this single cell source, which is a new concept for a field that aims to produce tissues with diverse structures and biomechanical functions.
This initial study sets the ground for new research that seeks to enhance the properties of the hESC-derived cartilage, direct their differentiation for specific cartilage applications, and determine the clinical applicability of these cells, including their safety. This work was funded by an unrestricted fund from Rice University.
Koay J. E., et al, Tissue Engineering with Chondrogenically Differentiated Human Embryonic Stem Cells, Stem Cells, Vol. 25 No. 9 September 2007