1. REGENERATION OF BONE TISSUE THROUGH STEM CELLS FOR THE TREATMENT OF OSTEOARTHRITIS Allen Wang and Sravan Rajathilak Arthritis Arthritis is a degenerative disease of the joints and is characterized by pain and disability, it causes inflammation and stiffness in the affected joint. Arthritis affects an estimated 52 million adults within the United States. Most of these arthritis patients are adults of advanced age. However, arthritis can affect the younger population as well. There are many risk factors that may increase the chance of developing arthritis such as being overweight, family history of arthritis, and injury. Different forms of arthritis affect the joint through different pathways. Osteoarthritis causes the deterioration of cartilage, while rheumatoid arthritis is an autoimmune disorder that first targets the synovium, or joint lining. Arthritis can be treated through different means, such as medication or even surgery. However, these treatment methods can only address the symptoms, not the actual problem itself. In order to address the actual disease, a new treatment method must be developed. One such method is through the use of stem cells. Stem Cells Stem cells are cells which have the ability to differentiate into almost any cell type. In order to do so, the stem cells must be induced to differentiate before they have any use. A stem cell is an unspecialized cell that cannot perform any true function for the body until specialization through differentiation. In the body, stem cells act as a repair mechanism which replaces cells that have been worn down through continuous use. In organs such as the intestines and other digestive organs, and the bone, stem cells will naturally grow and replace damaged or worn out tissue. Stem cells found within the bone marrow have the ability to differentiate into new bone cells. These stem cells are known as Mesenchymal stem cells. These stem cells are one of two stem cells identified within the bone marrow. Mesenchymal stem cells can be used to repair or replace the damaged tissue caused by osteoarthritis, providing a new solution to osteoarthritis. Osteoarthritis As explained before, arthritis is a degenerative disease of the joints and is characterized by pain and disability in the affected area. Osteoarthritis is the most common form of arthritis and affects any joint within the body. The most common joints affected are the hands, knees, hips, and spine. Osteoarthritis breaks down the cartilage that covers the bones found within the joint. Cartilage is a slippery tissue that covers the ends of bone in the joint and protects the bone by absorbing the shock caused by movement of the joint. Figure 1 An illustration of a healthy joint. No deterioration of the cartilage detected. Figure 1 An illustration of an arthritic joint. Deterioration of the cartilage is prevalent as well as damage to the bone. Types of stem cells Treatment of Osteoarthritis As mentioned before, stem cells can be used to treat osteoarthritis. Current techniques used for treating osteoarthritis do not have the ability to treat the disease itself. Rather, the current techniques focus on treating the symptoms of osteoarthritis and attempt to help the patient return to a normal life. The treatment tries to decrease the pain in the joints through medication, exercise, therapy, or even surgery. Current treatment methods also attempt to allow the patient regain flexibility in the affect joint. The treatment method does help patients, but simply treating the symptoms cannot help the patient completely recover from the disease. However, treating osteoarthritis through the use of Mesenchymal stem cells can potentially fix even the disease itself. Mesenchymal stem cells are found within the bone marrow and have the ability to differentiate into bone cells, and produce cartilage. Osteoarthritis causes the deterioration of the cartilage that covers the bone found within the joints. The cartilage absorbs the shock in the joints caused by movement. Without the cartilage present to protect the bones, the bones will grind against each other causing pain to the patient. Over time, the bone will also begin to wear down due to the friction. The risk of osteoarthritis increases with age, meaning more elderly have this disease. One of the current solutions to osteoarthritis is the replacement of the joint with a prosthesis. The prosthesis can be made of metal, plastic, or both and acts as a fake joint. The prosthesis will last anywhere from 10 to 15 years. In older patients, a prosthesis may last them the rest of their lives, but in many younger osteoarthritis patients, the prosthesis must be replaced multiple times. Rather than use a fake joint that needs replacement over time, a different solution would be the implanting a new knee into the patient with new cartilage. According to an article published in Biotechnology and Bioengineering, Mesenchymal stem cells were shown to be able to different into osteoblasts, a cell that synthesizes bone, on a honeycomb collagen scaffold. This study shows that Mesenchymal stem cells do have the capability to differentiate into bone cells and can be used for stem cell therapy in the treatment of osteoarthritis. In an article published in Arthritis & Rheumatism, it was concluded that local delivery of adult mesenchymal stem cells to injured joints stimulates regeneration of meniscal tissue and retards the progressive destruction normally seen in the caprine model of osteoarthritis. Osteoarthritis was induced on knee joints of the animals used in the test. After 6 weeks, one group of the test subjects received 10 million autologous cells suspended in a dilute solution of sodium hyaluronan. The control simply received sodium hyaluronan. The results were there was evidence of marked regeneration of the medial meniscus, and implanted cells were detected in the newly formed tissue. However, there was no evidence of repair of the ligament in any of the joints. This study showed that Mesenchymal stem cells do have a positive effect on patients with osteoarthritis, but cannot allow for a complete recovery. Mesenchymal stem cell therapy has been shown to be a possible treatment method for osteoarthritis, but current techniques are still in need of improvement. Ethics of Using Stem Cells Stem cell research has been a controversial topic since 1998 when scientists first isolated a human stem cell by destroying a human embryo. Stem cells that are created from the destruction of the embryo are known as human embryonic stem cells (hESC). These stem cells have been the topic of much debate. Questions embryonic stem cells raised such as when does a human’s life begin, is an embryo equivalent to a human child, can the destruction of a single embryo be justified if it can cure a countless number of patients, and does an embryo have human rights. Another issue that hESCs brought was whether it was possible to use the embryonic stem cells to recreate a human embryo and create a new human. In 2006, scientists learned how to induce a patient’s cells to act like embryonic stem cells. These cells are known as induced pluripotent stem cells (iPSC). Future Treatment for Osteoarthritis Arthritis is a degenerative of the joints. The disease causes pain for the patients and affects an estimated 52 million adults in the United States alone. Osteoarthritis is the most common form of arthritis and affects 27 million adults in the United States age 25 and older. Current treatments for osteoarthritis only addresses the symptoms but not the problem itself. By only focusing on reducing the pain and allowing the patient to regain movement in the affected joint, doctors are simply not considering the cause of the disease. A new treatment for osteoarthritis that can address the disease itself would be the use of Mesenchymal stem cells for the repair or replacement of damaged bone tissue. Mesenchymal stem cells are a type of adult stem cell that is found in the bone marrow and have the ability to differentiate into bone cells. By growing new bone tissue doctors can replace the tissue that was damaged by the osteoarthritis. The new bone tissue will also need a new layer of cartilage, in order to protect the bone from the friction of bones rubbing. This stem cell therapy is a permanent solution to osteoarthritis that also addressed the actual disease rather than just the symptoms. Human Embryonic Stem Cells (hESC) Found in the human embryo Discovered in 1998 Requires the destruction of the embryo Cause of ethical debate over user of stem cells Able to differentiate into many types of cells Induced Pluripotent Stem Cells (iPSC) Cells that are induced into a stem cell like state First reported in 2006 Able to differentiate into many cell types Use of iPSCs considered more ethical than use of hESCs. Adult Stem Cells Found in the human body among differentiated cells after development Repairs tissue when needed An example is the Mesenchymal stem cell Usually differentiates into the cells that it grows around