Bone Marrow Versus Adipose Autologous Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis

Study Overview
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Brief Summary
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Mesenchymal stem cells (MSC) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, bone marrow, and adipose tissue. The multipotent properties of MSCs make them a promising option for the treatment of osteoarthritis (OA). Bone marrow mesenchymal stem cells (BM-MSC) and adipose derived mesenchymal stem cells (AD-MSC) have been used separately to treat OA. The aim of the present study will be to compare in a randomized non blind controlled clinical trial 3 types of intra-articular injections containing MSC populations obtained from two clinically relevant sources: BM-MSC, AD-MSC and a combination of both BM-MSC and AD-MSC.

Detailed Description
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The aim of the present study will be to compare 3 types of intra-articular injections of MSC populations obtained from two clinically relevant sources: injections containing BM-MSC or AD-MSC or a combination of both BM-MSC,and AD-MSC in a randomized non blind clinical trial. To assess the efficacy and safety of 3 kind of MSC injections in relation to pain, function and quality of life in patients with knee OA. A total of 54 patients with the diagnosis of knee OA grade II and III will be recruited to receive a single intra-articular injection of MSC: Group 1 (n 18 patients) will receive BM-MSC, Group 3 (n 18 patients) will receive AD-MSC. Group 3 (18 patients) will receive a combination of BM-MSC and AD-MSC. A randomized non blind clinical trial with active control. For this purpose, the random number generator is 54, found on the RANDOM.ORG ® website (available at https://www.random.org/integers/)

Official Title
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Bone Marrow Versus Adipose Autologous Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Randomized Non Blind Controlled Clinical Trial

Conditions
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Osteo Arthritis Knee

Intervention / Treatment
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* Biological: bone marrow mesenchymal stem cells
* Biological: Adipose Mesenchymal stem cells
* Biological: bone marrow & adipose mesenchymal stem cells injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 to 70 years, with grade II and III knee OA, according to the Ahlbäck classification will be included. Minimal VAS pain score of 4. Chronic knee pain of mechanical origin. All patients who sign a specially prepared informed consent for this clinical trial. Exclusion Criteria: Varus or valgus knee mal alignment superior to 10°. OA grade IV according Ahlbäck classification. Bone marrow cancer like lymphoma. Severe anemia. Active infections. Pregnant patients. Inmune diseases such as Rheumatoid arthritis, gout or pseudogout arthritis, psoriasis. Bone diseases such as Kahler and Paget. Corticoesteroid and hyaluronic injections within the last 3 months. Knee surgery in the last 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of 54 patients with the diagnosis of knee OA grade II and III will be recruited to receive a single intra-articular injection of MSC: Group 1 (n 18 patients) will receive BM-MSC, Group 2 (n 18 patients) will receive AD-MSC. Group 3 (18 patients) will receive a combination of BM-MSC and AD-MSC.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: bone marrow mesenchymal stem cell<br>Bone marrow mesenchymal stem cells 10 cc by intra articular injection once | Biological: bone marrow mesenchymal stem cells<br>* intrarticular bone marrow mesenchymal stem cells injection<br>|
| Active Comparator: adipose mesenchymal stem cells<br>Stromal vascular factor from adipose mesenchymal stem cells 10 cc by intra articular injection once | Biological: Adipose Mesenchymal stem cells<br>* intrarticular adipose mesenchymal stem cells injection<br>|
| Active Comparator: Bone marrow and Adipose mesenchymal stem cells<br>Bone marrow and Stromal vascular factor from adipose mesenchymal stem cells 5 cc each one, by intra articular injection once. | Biological: bone marrow & adipose mesenchymal stem cells injection<br>* intrarticular bone marrow and adipose stem cells injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| knee pain assessed by Visual Analogue Scale. | psychometric response scale which used in questionnaires. It is a measurement instrument for subjective characteristics of pain . Score from O to 10. O indicate no pain, and 10 indicate the worst pain. | 12 months | 
| knee function assessed by WOMAC (Wester Ontario McMaster Osteoarthritis Index). quosteionary. | The Index contains 24 questions five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). Individual question responses are assigned a score of between 0 (extreme) and 4 (None). Individual question scores are then summed to form a raw score ranging from 0 (worst) to 96 (best). Finally, raw scores are normalized by multiplying each score by 100/96. This produces a reported WOMAC Score of between 0 (worst) to 100 (best). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative T2-Mapping Evaluation of Changes in Cartilage Matrix | MRI T2 mapping of the cartilage is a non-invasive functional imaging technique delivering cartography of the T2 relaxation time of the cartilage without any contrast injection. It is sensitive to tissue anisotropy, and provides compositional information on the cartilage collagen network, water content and proteoglycans concentration. | 6 months after procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cell