Repairing Cartilage With Fat-Based Stem Cells May Be Feasible With New Technology

Head-to-head comparisons between bone marrow and fat stem cells have shown that bone marrow stem cells consistently outperform fat stem cells. As I have written in past posts, the present protocols for inducing cartilage from mesenchymal stem cells were developed using bone marrow stem cells. Therefore, the fact that bone marrow stem cells outperform fat stem cells with it comes to cartilage formation is no surprise.

In a study in New Zealand White rabbits, bone marrow stem cells outperformed fat stem cells when it came to the repair the cartilage defects in the knee joint. See Li Q, Tang J, Wang R, Bei C, Xin L, Zeng Y, Tang X. “Comparing the chondrogenic potential in vivo of autogeneic mesenchymal stem cells derived from different tissues.” Artif Cells Blood Substit Immobil Biotechnol. 2011 Feb;39(1):31-8. Here again, the system for chondrocyte differentiation system used was developed with, by, and for bone marrow mesenchymal stem cells. Thus the ability of these cells to outperform fat stem cells says nothing about the ability of fat-based mesenchymal stem cells to form cartilage in alternative culture systems.

Because fat-based stem cells are highly accessible and unlikely to be rejected by the immune system, there is a deep desire to efficiently convert fat-based stem cells into cartilage. Unfortunately, this task is not as straightforward as previously believed. As it turns out, fat-derived stem cells secrete molecules that actually inhibit cartilage formation. However, new research has found that if fat-based stem cells are pre-treated with antibodies that neutralize Vascular Endothelial Growth Factor (VEGF) and growing them in nutrients that are specifically designed to promote cartilage formation can counteract the effects of these molecules.

Chondrocytes make and maintain healthy cartilage. However, damage and diseases, such as osteoarthritis, can destroy cartilage and this can result in pain, compromising the patient’s mobility.

Professor Barbara Boyan, and her colleagues from the Georgia Institute of Technology showed that adipose (fat) stem cells (ASCs) secrete large amounts of factors. Some of these factors, especially the growth factor VEG, prevents cartilage regeneration and actually causes the death (apoptosis) of chondrocytes.

However, by treating ASCs with a media designed to encourage the differentiation of fat-based stem cells into cartilage cells reduced the amount of these secreted factors and prevented the growth of blood vessels. Also, the fat-based stem cells were treated with an antibody that neutralizes VEGF, and this pretreatment prevented chondrocyte death.

Professor Boyan said: “Non-treated ASCs actually impeded healing of hyaline cartilage defects, and although treating ASCs improved the situation they added no benefit compared to cartilage allowed to heal on its own. However we only looked at cartilage repair for a week after treatment. Other people have shown that two to six weeks is required before the positive effect of ASCs on cartilage regeneration is seen.”

Therefore, fat-based stem cells might be able to help repair damaged cartilage, and careful handling plus pre-treatment can help ensure a positive result.

See: “Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration,” Christopher SD Lee et al.; Stem Cell Research & Therapy, 24 August 2012, 3:35, DOI:10.1186/scrt126

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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).