William G. Rodkey, DVM
Director of The Center for Translational and Regenerative Medicine Research (CTRMR)
The purpose of our Translational and Regenerative Medicine Research is to gain a better understanding of factors that lead to:
- degenerative joint disease
- improved healing of soft tissues such as ligaments, tendons, articular cartilage, and meniscus cartilage, and
- novel and untried approaches of treatment modalities
Our focus is to develop new surgical techniques, innovative adjunct therapies, rehabilitative treatments, and related programs that will help to delay, minimize, or prevent the development of joint degeneration and osteoarthritis. In 2008, we collaborated with various educational institutions, predominantly Colorado State University. Our concerted efforts have significant potential to slow the degenerative processes while leading the way to enhance healing and regeneration of injured tissues.
The specialty discipline of regenerative medicine is an exciting one that has gained global attention and has led to many new and innovative techniques by scientists around the world. One of the broad goals of this work, and our main focus, can be stated simply as joint preservation. In 2008, we continued our efforts on regeneration of an improved tissue for resurfacing of articular cartilage (chondral) defects that typically lead to joint degeneration and osteoarthritis. We have worked in collaboration with Drs. Wayne McIlwraith and David Frisbie at Colorado State University. The focus of these efforts was on the use of adult autogenous (one’s own) mesenchymal stem cells (MSCs) to stimulate and enhance healing of injured articular cartilage.
The following provides some background information and a summary of our most recent findings. This work is ongoing, and the encouraging results presented here will allow us to continue to focus on this work in the coming years.
Osteoarthritis (OA) is a debilitating, progressive disease characterized by the deterioration of articular cartilage accompanied by changes in the subchondral bone and soft tissues of the joint. Traumatic injury to joints is also often associated with acute damage to the articular cartilage. Unfortunately, hyaline articular (joint) cartilage is a tissue with very poor healing or regenerative potential. Once damaged, articular cartilage typically does not heal, or it may heal with functionless fibrous scar. Such tissue does not possess the biomechanical and biochemical properties of the original hyaline cartilage; hence, the integrity of the articular surface and normal joint functions are compromised. The result often is OA. Because of the tremendous economic costs of OA, our efforts in the area of regenerative medicine have been to address methods to ameliorate its impact.
As noted above, our major effort this year involves the use of adult autogenous mesenchymal stem cells that come from the patients themselves as an adjunct to microfracture. That is, there is no use of embryonic stem cells, nor is there a necessity to find donors. Each patient is his/her own source of the stem cells. We believe that there is a simple and inexpensive way to produce these stem cells, and then when added to the microfracture site, these stem cells will significantly enhance the speed and intensity of the healing process. If we can prove this method successful, it is likely that the rehabilitation protocol can be greatly accelerated, thus minimizing discomfort, lost time away from work or sports, and overall financial costs. And of course, we also hope that such treatment could help prevent or at least minimize degenerative osteoarthritis after chondral injury.
The primary objective of this ongoing research project is to test the potential of bone marrow derived MSCs to augment the healing response gained in full-thickness cartilage defects that have undergone the microfracture procedure. The working hypothesis is that the combined effects of intraarticular injection of autogenous bone marrow derived MSCs with microfracture will promote superior healing in full-thickness defects compared to microfractured defects alone, and furthermore, the healing with the MSCs will be superior to that observed in our earlier studies referenced above. We are using our well-established equine model to pursue the goals and objectives of this study. We are confident that we can definitively address the main question: Do bone marrow derived mesenchymal stem cells enhance the cartilage repair process when used in conjunction with the microfracture procedure?
This study is being carried out in twelve horses in conjunction with our collaborators at Colorado State University. Full-thickness cartilage lesions were made in each knee (stifle) joint and then microfractured in a standard manner. At the same time, bone marrow aspirates were obtained, MSCs were isolated, and the MSCs were expanded in culture for the next three weeks. After three weeks, randomly and in a fashion blinded to the investigators, one joint received an injection of the expanded MSCs while the opposite joint received a placebo control. Four months later, relook arthroscopy was performed on all of the joints, and photographic documentation of the joints was carried out. All of the tissue will be harvested at twelve months. Not until all samples have been analyzed will the investigators be allowed to know which joints received which treatment. We are all very excited to bring this study to its conclusion and find out if adult autogenous MSCs can make a significant difference in cartilage healing, and thus help prevent or at least minimize degenerative osteoarthritis after injury to the cartilage.
These exciting times and earlier outcomes are encouraging, and we believe that very important research results lie just ahead for the Basic Science Research group and the Institute.