Stem Cell-Based Therapy for Cartilage Regeneration and Osteoarthritis

Stem Cell-Based Therapy for Cartilage Regeneration and Osteoarthritis

Funding Type: 
Early Translational I
Grant Number: 
TR1-01216
Investigator: 
Approved funds: 
$3,118,431
Disease Focus: 
Arthritis
Bone or Cartilage Disease
Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
Cell Line Generation: 
iPS Cell
Public Abstract: 
Arthritis is the result of degeneration of cartilage (the tissue lining the joints) and leads to pain and limitation of function. Arthritis and other rheumatic diseases are among the most common of all health conditions and are the number one cause of disability in the United States. The annual economic impact of arthritis in the U.S. is estimated at over $120 billion, representing more than 2% of the gross domestic product. The prevalence of arthritic conditions is also expected to increase as the population increases and ages in the coming decades. Current treatment options for osteoarthritis is limited to pain reduction and joint replacement surgery. Stem cells have tremendous potential for treating disease and replacing or regenerating the diseased tissue. This grant proposal will be valuable in weighing options for using stems cells in arthritis. It is very important to know the effect of aging on stems cells and how stem cell replacement might effectively treat the causes of osteoarthritis. We will establish conditions for stem cells to repair a surgical defect in laboratory models and test efficacy in animal models of cartilage defects. We will demonstrate that stem cells have anti-arthritic effects, establish optimal conditions for stem cells to migrate into the diseased tissue and initiate tissue repair, and test efficacy in animal models of arthritis. We will plan safety and efficacy studies for the preclinical phase, identify collaborators with the facilities to obtain, process, and provide cell-based therapies, and identify clinical collaborators in anticipation of clinical trials. If necessary we will also identify commercialization partners. Stem cells fight disease and repair tissues in the body. We anticipate that stem cells implanted in arthritic cartilage will treat the arthritis in addition to producing tissue to heal the defect in the cartilage. An approach that heals cartilage defects as well as treats the underlying arthritis would be very valuable. If our research is successful, this could lead to first ever treatment of osteoarthritis with or without stem cells. This treatment would have a huge impact on the large numbers of patients who suffer from arthritis as well as in reducing the economic burden created by arthritis.
Statement of Benefit to California: 
California has been at the forefront of biomedical research for more than 40 years and is internationally recognized as the biotechnology center of the world. The recent debate over the moral and the ethical issues of stem cell research has hampered the progress of scientific discoveries in this field, especially in the US. The CIRM is a unique institute that fosters ethical stem cell research in California. The CIRM also serves as an exemplary model for similar programs in other states and countries. This grant proposal falls under the mission statement of the CIRM for funding innovative research. The proposal will generate highly innovative and effective therapies for cartilage degeneration and osteoarthritis and will explore the potential use of tissue-engineered products from stem cells. If successful, this will further validate the significance of the CIRM program and will help maintain California's leading position at the cutting edge of biomedical research. Reducing the medical and economic burden of large numbers of patients who suffer from arthritis would is of significant benefit.
Progress Report: 

Year 1

Arthritis is the result of degeneration of cartilage (the tissue lining the joints) and leads to pain and limitation of function. The annual economic impact of arthritis in the U.S. is estimated at over $120 billion, representing more than 2% of the gross domestic product. The prevalence of arthritic conditions is also expected to increase as the population increases and ages in the coming decades. Current treatment options for osteoarthritis are limited to pain reduction and joint replacement surgery. Stem cells have tremendous potential for treating disease and replacing or regenerating the diseased tissue. In this grant we proposed a series of experiments to develop stems cells for use in arthritis. We have met all the milestones we proposed in the first year of the grant application. We have differentiated embryonic stem cells into cells that can generate cartilage tissue similar to that generated by normal cartilage cells. We have induced pluripotency in adult human cells obtained from skin. Inducing pluripotency means transforming adult cells into cells that function very similar to embryonic stem cells. The advantage of this approach is that it removes the need for embryos as source of cells and greatly reduces the risk of rejection by the patient. We have also induced pluripotency in adult human cells obtained from joint cartilage. We believe that the original source of the cells may make a significant difference in the quality of the tissue being regenerated. For example, pluripotent cells generated from cartilage cells will likely produce a better quality of cartilage tissue than pluripotent cells generated from skin cells. We have established conditions for successful repair of surgical defects using stem cells in laboratory models. We are currently working on an appropriate surgical technique for the in vivo experiments, which will involve implanting these cells in cartilage defects in live animals. We have completed our experiments as outlined in our grant submission, which was the goal to enhance the development of cartilage by testing of various stem cells lines. The next phase of our project will be to prepare for the animal experiments to test the viability of our laboratory experiments that would result in cartilage repair.

Year 2

Our initial application established the goals of our project and the reasons for our study. Arthritis is the result of degeneration of cartilage (the tissue lining the joints) and leads to pain and limitation of function. Arthritis and other rheumatic diseases are among the most common of all health conditions and are the number one cause of disability in the United States. The annual economic impact of arthritis in the U.S. is estimated at over $120 billion, representing more than 2% of the gross domestic product. The prevalence of arthritic conditions is also expected to increase as the population increases and ages in the coming decades. Current treatment options for osteoarthritis are limited to pain reduction and joint replacement surgery. Stem cells have tremendous potential for treating disease and replacing or regenerating the diseased tissue. In this project our objective is to use cells derived from stems cells to treat arthritis. We have completed our experiments as per our proposed timeline and have met milestones outlined in our grant submission. We have established conditions for converting stem cells into cartilage tissue cells that can repair bone and cartilage defects in laboratory models. We have identified several cell lines with the highest potential for tissue repair. We optimized culture conditions to generate the highest quality of tissue. In our initial experiments we found no evidence of cell rejection response in animals. We are now in the process of testing efficacy of the three most promising cell lines in regenerating healthy tissue in animals with cartilage defects. In the next phase of our project we will plan safety and efficacy studies for the preclinical phase, identify collaborators with the facilities to obtain, process, and provide cell-based therapies, and identify clinical collaborators in anticipation of clinical trials. If necessary we will also identify commercialization partners. We anticipate that stem cells implanted in arthritic cartilage will treat the arthritis in addition to producing tissue to heal the defect in the cartilage. An approach that heals cartilage defects as well as treats the underlying arthritis would be very valuable. If our research is successful, this could lead to first ever treatment of osteoarthritis with or without stem cells. This treatment would have a huge impact on the large numbers of patients who suffer from arthritis as well as in reducing the economic burden created by arthritis.

Year 3

Our initial application established the goals of our project and the reasons for our study. Arthritis is the result of degeneration of cartilage (the tissue lining the joints) and leads to pain and limitation of function. Arthritis and other rheumatic diseases are among the most common of all health conditions and are the number one cause of disability in the United States. The annual economic impact of arthritis in the U.S. is estimated at over $120 billion, representing more than 2% of the gross domestic product. The prevalence of arthritic conditions is also expected to increase as the population increases and ages in the coming decades. Current treatment options for osteoarthritis are limited to pain reduction and joint replacement surgery. Stem cells have tremendous potential for treating disease and replacing or regenerating the diseased tissue. In this project our objective is to use cells derived from stems cells to treat arthritis. We have completed our experiments as per our proposed timeline and have met milestones outlined in our grant submission. We have established conditions for converting stem cells into cartilage tissue cells that can repair bone and cartilage defects in laboratory models. We have identified several cell lines with the highest potential for tissue repair. We optimized culture conditions to generate the highest quality of tissue. In our initial experiments we found no evidence of cell rejection response in animals. We are now in the process of testing efficacy of the three most promising cell lines in regenerating healthy tissue in animals with cartilage defects. In the next phase of our project we will plan safety and efficacy studies for the preclinical phase, identify collaborators with the facilities to obtain, process, and provide cell-based therapies, and identify clinical collaborators in anticipation of clinical trials. If necessary we will also identify commercialization partners. We anticipate that stem cells implanted in arthritic cartilage will treat the arthritis in addition to producing tissue to heal the defect in the cartilage. An approach that heals cartilage defects as well as treats the underlying arthritis would be very valuable. If our research is successful, this could lead to first ever treatment of osteoarthritis with or without stem cells. This treatment would have a huge impact on the large numbers of patients who suffer from arthritis as well as in reducing the economic burden created by arthritis.

Year 4

Our initial application established the goals of our project and the reasons for our study. Arthritis is the result of degeneration of cartilage (the tissue lining the joints) and leads to pain and limitation of function. Arthritis and other rheumatic diseases are among the most common of all health conditions and are the number one cause of disability in the United States. The annual economic impact of arthritis in the U.S. is estimated at over $120 billion, representing more than 2% of the gross domestic product. The prevalence of arthritic conditions is also expected to increase as the population increases and ages in the coming decades. Current treatment options for osteoarthritis are limited to pain reduction and joint replacement surgery. Stem cells have tremendous potential for treating disease and replacing or regenerating the diseased tissue. In this project our objective is to use cells derived from stems cells to treat arthritis. We have completed our experiments as per our proposed timeline and have met milestones outlined in our grant submission. We have established conditions for converting stem cells into cartilage tissue cells that can repair bone and cartilage defects in laboratory models. We have identified several cell lines with the highest potential for tissue repair. We optimized culture conditions to generate the highest quality of tissue. In our initial experiments we found no evidence of cell rejection response in vivo. We have testing efficacy of the most promising cell lines in regenerating healthy repair tissue in cartilage defects and have selected a preclinical candidate. The next step is to plan safety and efficacy studies for the preclinical phase, identify collaborators with the facilities to obtain, process, and provide cell-based therapies, and identify clinical collaborators in anticipation of clinical trials. If necessary we will also identify commercialization partners. We also anticipate that stem cells implanted in arthritic cartilage will treat the arthritis in addition to producing tissue to heal the defect in the cartilage. An approach that heals cartilage defects as well as treats the underlying arthritis would be very valuable. If our research is successful, this could lead to first treatment of osteoarthritis that alters the progression of the disease. This treatment would have a huge impact on the large numbers of patients who suffer from arthritis as well as in reducing the significant economic burden created by arthritis.

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