Study to Compare Efficacy and Safety of Cartistem and Microfracture in Patients With Knee Articular Cartilage Injury
Study to Compare Efficacy and Safety of Cartistem and Microfracture in Patients With Knee Articular Cartilage Injury
The purpose of the study is to assess and compare the safety and efficacy of the
 allogeneic-unrelated umbilical cord blood-derived mesenchymal stem cell product (Cartistem®)
 to that of a microfracture treatment in patients with articular cartilage defect or injury.
The cartilage is a unique avascular, aneural tissue that does not regenerate easily once
 damaged. Chondral defects or damages to articular cartilages due to accidents, necrosis of
 subchondral bone tissue, or arthritis have become some of the more common disorders today.
 About 15% of the world's population is reportedly suffering from cartilage and joint damages
 such as degenerative arthritis and rheumatoid arthritis. As population aging progresses and
 as more young people start taking up active sports, the size of the target patient group is
 also growing. However, despite ongoing research, an effective treatment for cartilage defects
 is yet to be discovered. Various different types of treatments are currently in use, such as
 drug therapy, arthroscopy, and artificial joint surgery. However, they all fail to address
 the root cause. Complete treatment, or regeneration of damaged or defective cartilage is
 impossible and continuous drug administration or secondary surgeries are required in many
 cases.

 As a way of regenerating the damaged or defective cartilage tissue, treatment of localized
 damage to articular cartilage using autologous chondrocytes is currently under review. A few
 life science companies both home and abroad are marketing this method of treatment called
 'autologous chondrocyte transplant'. The treatment involves the extraction of healthy
 cartilage tissue from the patient which is then cultured and transplanted into the damaged
 site.

 However, this treatment requires the extraction of chondrocytes directly from the patient and
 thus causes trauma in healthy articular cartilage. Also, this type of treatment cannot be
 applied to large lesions, nor is the efficacy satisfactory in patients over the age of 40
 whose cellular activation levels are low. Thus, autologous chondrocyte transplant is rather
 limited in the number of cells harvested and their activation level and is therefore
 restricted in terms of treatment site, severity of the condition, and the size of lesion. The
 current technology allows the application of treatments in local cartilage defects but not in
 degenerative arthritis or rheumatoid arthritis. The technology needs to be taken up to
 another level in order to benefit such prevalent arthritic disorders. Treatments using stem
 cells do not cause damage to healthy articular cartilage as they don't require the harvesting
 of healthy cartilage tissues from the patients. Moreover, the number of successfully cultured
 cells is larger due to the excellent proliferation capability of stem cells and thus, mass
 supply is possible.

 This clinical trial for the stem cell therapies is essential because treatment of cartilage
 defects with umbilical cord blood-derived mesenchymal stem cells, known to have the highest
 level of activity among all adult stem cells, opens the possibility of articular cartilage
 regeneration even for aged patients and patients with large lesions unable to benefit from
 existing treatments.

 The biggest challenge faced by nations competing in the field of "tissue differentiation and
 regeneration using stem cells" is the question of whether or not the use of embryonic stem
 cells is ethical. Chondrogenesis using umbilical cord blood-derived mesenchymal stem cells
 can not only avoid similar challenges, but also present an innovative treatment mode with
 significant clinical implications for the patients.

 In the clinical study, mesenchymal stem cells will be isolated from umbilical cord blood and
 cultured, mixed with semi- solid polymer, and administered into the cartilage tissue lesion
 by orthopedic surgery in order to stimulate the regeneration of defective cartilage tissue
 and to improve their functions.
Inclusion Criteria:

 -  Patients with knee joint cartilage defect or injury of ICRS (International Cartilage
 Repair Society) Grade 4 confirmed by arthroscopy (At screening, patients diagnosed as
 such with an MRI may be included)

 -  Male or female patients at least 18 years of age

 -  Patients whose lesion (unilateral joint) is 2 ㎠ ~ 9㎠ in size

 -  Patients with articular swelling, tenderness and active range of motion of Grade 2 or
 below

 -  Patients with pain in affected joint of 60-mm or below on a 100-mm VAS (visual
 analogue scale)

 -  Patients with adequate blood coagulation activity, PT(INR) < 1.5, APTT <1.5×control

 -  Patients with adequate renal function, Creatinine ≤ 2.0 ㎎/㎗, levels of proteinuria
 measured with Dipstick: trace or less

 -  Patients with adequate hepatic function, Bilirubin ≤ 2.0 ㎎/㎗, AST/ALT ≤ 100 IU/L

 -  Patients who have received no surgery or radiation therapy in the affected joint
 within the past 6 six weeks, and have recovered from the side effects of such past
 treatments

 -  Female patients of childbearing potential must agree to practice adequate methods of
 birth control to prevent pregnancy during the study

 -  Patients whose physical examination results show no ligament instability of Grade II
 or above (Grade 0: none, Grade I: 0-5 mm, Grade II: 5-10 mm, Grade III: >10 mm)

 -  Patients who voluntarily agreed to enroll in the study and signed an informed consent
 form

 Exclusion Criteria:

 -  Patients with autoimmune disease or the medical history

 -  Patients with infections requiring parenteral administration of antibiotics

 -  Patients with myocardial infarction, ischemic heart failure, other serious heart
 conditions or uncontrolled hypertension, or any medical history of such diseases

 -  Patients with serious internal diseases

 -  Patients who are currently pregnant or nursing

 -  Patients with psychotic diseases, epilepsy, or any history of such diseases

 -  Patients with alcohol abuse

 -  Patients who smoke excessively

 -  Patients with chronic inflammatory articular diseases such as rheumatoid arthritis

 -  Patients who were enrolled in any other clinical trials within the past four weeks

 -  Patients who had been administered with immunosuppressants such as Cyclosporin A or
 azathioprine within the past six weeks

 -  Patients whose physical examination results show ligament instability of Grade II or
 above (Grade 0: none, Grade I: 0-5 mm, Grade II: 5-10 mm, Grade III: >10 mm)

 -  Patients with a known history of hypersensitivity/allergy to gentamicin

 -  Patients who the principal investigator considers inappropriate for the clinical trial
 due to any other reasons than those listed above