Clinical trial NCT00891501: The Use of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Articular Cartilage Defects
Official title: The Use of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Articular Cartilage Defects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Degenerative Arthritis
Chondral Defects
Osteochondral Defects
Keywords: autologous bone marrow mesenchymal stem cells
cartilage repair
osteoarthritis
osteochondral defects
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2009-05-01
Enrollment: 25
Sex: ALL
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is conducted to assess whether implanting autologous, culture-expanded, mesenchymal stem cells obtained from the bone marrow of patients with early osteoarthritis, cartilage defects or cartilage and underlying bone and cartilage (osteochondral) defects in joints is effective in the treatment of such conditions and alleviation of patients symptoms.

Detailed description: All procedures are carried out after obtaining informed written consent from patients. Bone marrow is aspirated from the iliac crest (hip bone) of patients with osteochondral defects intraoperatively under complete sterile, aseptic conditions and under proper anaesthesia (general, local). The bone marrow aspirate is placed in tubes and transferred under aseptic conditions to the Tissue Culture Unit in the Biochemistry Department at the Cairo University School of Medicine where it is processed and bone marrow mesenchymal stem cells are isolated and grown in culture for 2-3 weeks. After this time interval, the cells are reprocessed and the cell pellet is obtained. Implantation of the cell pellet into the osteochondral defect of the joint after embedding it on a proper scaffold is performed followed by subsequent defect coverage with an autologous periosteal flap obtained from the proximal tibia to seal the defect and maintain the cell pellet in place. The patients will be assessed clinically with scoring systems preoperatively as well as 6 and 12 months postoperatively to assess relief of symptoms and joint function. Radiological assessment (X-rays and MRIs)of the affected joints will be performed at the same time points aforementioned to assess integrity of the formed cartilage. Second look arthroscopy and biopsy will also be performed to histologically assess the repair tissue and grade it via arthroscopic grading system according to the International Cartilage Repair Society guidelines.

Eligibility criteria: Inclusion Criteria:

* Active patients (15 to 55 years).
* An isolated osteochondral defect (i.e., in a joint with an otherwise healthy articular surface - with cartilage on the opposing surface no more than grade 1 or 2 Outerbridge at the most.
* A defect that is 1 - 4 cm2 or more (up to 16 cm2).

Exclusion Criteria:

* Patients younger than 15 years and older than 55 years.
* Diffuse and advanced articular cartilage degeneration of the joint
* Axial malalignment, meniscal pathology, and ligamentous instability are RELATIVE contraindications that have to be dealt with primarily either concomitantly or before the transplantation during 1 of the 2 stages of the procedure. Refusal of the patient to address these conditions in presence of a cartilage lesion is a criterion for exclusion from the study.
* Kissing lesions (i.e., on both opposing surfaces of a joint).
* Existing infection in or around the joint \& lesions of infectious or oncologic etiology.
* Debilitated patients.
* Immunocompromised patients.
* Patients with autoimmune disorders \& systemic inflammatory disease.
* Preoperative poor neurological or vascular status of the affected limb.
* Specific contraindications include the use of tobacco and medications that may impair cell proliferation, such as NSAIDs and immunosuppressive drugs. Patients must be nicotine-free (stop smoking) prior to the procedure, as studies have shown that the oxidative effect of smoking impairs cell function and subsequent healing.

Primary outcomes:
measure: Improvement in Clinical Scores and Radiological images
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Deaprtment of Orthopedic Surgery and Tissue Culture Unit of the Department of Medical Biochemistry - Cairo University School of Medicne - Kasr Al Ainy Hospitals -Al-Saray Street, El Manial
Study officials:
affiliation: Department of Orthopedic Surgery Cairo University School of Medicine
name: Abdel Aziz El Singergy, M.D
role: STUDY_DIRECTOR
affiliation: Department of Orthopedic Surgery Cairo University School of Medicne
name: Amgad M Haleem, M.Sc(Ortho)
role: PRINCIPAL_INVESTIGATOR
affiliation: Tissue Culture Unit - Department of Medical Biochemistry - Cairo University School of Medicine
name: Hazem M Atta, Ph.D
role: STUDY_DIRECTOR
References:
citation: Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1994 Apr;76(4):579-92. doi: 10.2106/00004623-199404000-00013.
citation: Wakitani S, Mitsuoka T, Nakamura N, Toritsuka Y, Nakamura Y, Horibe S. Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports. Cell Transplant. 2004;13(5):595-600. doi: 10.3727/000000004783983747.
citation: Kuroda R, Ishida K, Matsumoto T, Akisue T, Fujioka H, Mizuno K, Ohgushi H, Wakitani S, Kurosaka M. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage. 2007 Feb;15(2):226-31. doi: 10.1016/j.joca.2006.08.008. Epub 2006 Sep 26.