Knee osteoarthritis, also known as gonarthrosis, is one of the most common causes of chronic pain and loss of mobility in the adult population. When the condition progresses to stages II, III, or IV, many patients are told that joint replacement is the only option.
However, the clinical evidence accumulated over the past two decades shows that, in selected patient profiles, there are regulated alternatives that can be considered before surgery.
At ITRT, we develop advanced therapy medicinal products with cultured mesenchymal cells (CMC), evaluated in clinical trials authorized by the Spanish Agency of Medicines and Medical Devices (AEMPS), which have proven to be a safe alternative in specific cases.
What is knee osteoarthritis?
Knee osteoarthritis is a degenerative process that affects the articular cartilage and, progressively, the subchondral bone, menisci, ligaments, and synovial membrane. It is not simply passive knee wear and tear: it involves a complex biological alteration with a chronic inflammatory component.
Characteristic symptoms include:
- Mechanical pain
- Stiffness after rest
- Joint crepitus (sounds and sensations when moving the joint)
- Effusion and progressive loss of function
In more advanced stages, knee damage can significantly limit quality of life.
Grades of gonarthrosis: what do stages II, III, and IV mean?
The Kellgren-Lawrence radiological classification grades knee osteoarthritis on a four-grade scale, based on joint space narrowing, the presence of osteophytes, and subchondral bone involvement.
From grade II onward, the disease already causes significant functional limitations and is usually the point at which patients begin to look for therapeutic alternatives:
Grade II: early gonarthrosis with visible involvement
This stage is characterized by mild joint space narrowing and osteophytes (small bony growths or protrusions that form at the edges of joints) already visible on X-ray. Patients typically report moderate mechanical pain when climbing stairs, after prolonged activity, or when getting up after rest. This is the grade at which advanced imaging allows the most precise characterization of the knee damage before it progresses.
Grade III: moderate knee wear and tear with functional limitation
This stage involves moderate to severe joint space narrowing, subchondral bone sclerosis, and possible early deformity. Pain becomes more constant, occurs during everyday activities, and interferes with nighttime rest. At this grade, knee wear and tear is usually accompanied by meniscal involvement and changes in the synovial membrane that should be evaluated together.
Grade IV: advanced knee osteoarthritis
This grade corresponds to marked joint space loss, extensive sclerosis, and clear bone deformity. Function is significantly compromised and, in many cases, joint replacement is recommended. Not all grade IV cases are equivalent: compartmental involvement, the condition of the menisci, and the presence or absence of joint effusion determine the prognosis and the possibility of considering alternatives before surgery.
Why is MRI essential in evaluating knee osteoarthritis?
X-rays classify the grade but do not characterize the cartilage, menisci, subchondral bone, or synovial membrane. For this reason, evaluation at ITRT requires a recent 3 Tesla MRI: these systems double the signal-to-noise ratio compared to 1.5 Tesla systems, allow for thinner slices, and improve the detection of subtle cartilage lesions. This is the resolution needed to determine whether a case meets the criteria required by the AEMPS and to objectively document subsequent structural changes.
Beyond knee wear and tear: which biologic treatments are regulated?
There is currently considerable terminological confusion between unregulated procedures (PRP, minimally manipulated cell injections, non-cultured adipose tissue derivatives) and advanced therapy medicinal products based on cultured mesenchymal cells (CMC).
Under the European regulatory framework, CMC are classified as medicinal products in accordance with Regulation (EC) 1394/2007. This entails:
- Manufacturing in a cleanroom under Good Manufacturing Practice (GMP) standards.
- Cell characterization, quality controls, and product certification.
- Individual AEMPS authorization, patient by patient and batch by batch.
- Full traceability of the process.
This regulatory distinction is the main guarantee of clinical safety and reproducibility.
See also: Which cell therapies can be considered legal and regenerative?
ITRT clinical evidence in knee osteoarthritis with cultured mesenchymal cells
ITRT has sponsored and participated in several AEMPS-authorized clinical trials in grade II–IV gonarthrosis, with publications in international peer-reviewed scientific journals:
- Single-center phase I-II trial with autologous CMC (MSV, Valladolid). Published in Transplantation (Orozco et al., 2013) and with two-year follow-up (Transplantation, 2014). Results confirmed the safety profile, significant clinical improvement in pain and function, and objective improvement in cartilage quality assessed by quantitative MRI (T2 mapping), sustained at two years. An extended series of 50 cases with clinical and MRI evaluation was published in the Journal of Stem Cell Research & Therapy (Soler Rich et al., 2015).
- Multicenter phase IIb trial with allogeneic CMC. Published in Transplantation (Vega et al., 2015), comparing allogeneic cells against an active control with hyaluronic acid in patients with knee osteoarthritis. The study confirmed the safety profile of allogeneic CMC and showed clinical improvement in pain and function superior to the active control.
- Phase IIa trial with cryopreserved CMC (MSV-Crio). Final results published in The Knee (Soler et al., 2016), confirming the safety profile and findings consistent with cartilage regeneration observed by MRI.
- Multicenter phase III ARTROCELL trial (EudraCT 2019-002446-21), currently ongoing, comparing allogeneic CMC against autologous CMC and against hyaluronic acid as an active control. Results have not yet been published.
This line of research remains active, with recent publications and participation in international scientific networks. It is important to note that knee osteoarthritis is the most complex indication in cell therapy, since it simultaneously affects the cartilage, menisci, subchondral bone, and synovial membrane. Results vary depending on clinical stage, compartmental involvement, and the patient’s medical history.
What clinical requirements apply for evaluating CMC treatment?
Not every patient with knee osteoarthritis is a candidate. Evaluation is individualized and based on:
- Diagnostic imaging: a recent 3 Tesla MRI is essential to evaluate the cartilage, menisci, subchondral bone, and synovial membrane.
- Complete medical history: we need to understand how long the knee injury has been present, previous treatments, comorbidities, and functional activity level.
- Clinical and radiological stage: grades II and III generally show a better prognostic profile; advanced grade IV cases with severe deformity require stricter evaluation.
- Absence of exclusion criteria: certain oncologic, infectious, or immunologic histories may contraindicate the procedure.
The individual AEMPS authorization is only requested when the medical team has verified that the case meets the necessary criteria. Requesting an evaluation does not imply that the treatment will be carried out.
Every case of knee osteoarthritis is different. The indication for treatment with cultured mesenchymal cells (CMC) requires an individualized evaluation of the medical history and imaging studies.
If you are considering alternatives to joint replacement and would like the ITRT medical team to review your case, you can send your recent MRI and a brief clinical summary to cells@itrt.es. We will let you know whether your profile meets the criteria for a specialized medical evaluation at Centro Médico Teknon, in Barcelona.
Frequently asked questions
Are cultured mesenchymal cells (CMC) the same as "stem cells"?
No. CMC are an advanced therapy medicinal product, manufactured under GMP standards, cellularly characterized, and individually authorized by the AEMPS. The generic term “stem cells” is used imprecisely in unregulated contexts and is not equivalent.
Are CMC the same as platelet-rich plasma (PRP)?
No. PRP is a product derived from the patient’s own blood. It is not an advanced therapy medicinal product, does not require GMP manufacturing or individual AEMPS authorization, and therefore the results are not the same.
Do CMC replace knee replacement surgery?
Not always. In certain clinical profiles, CMC may be considered as an alternative prior to joint replacement surgery, but the indication for surgery is determined by the medical team evaluating each individual case.
Where is the procedure performed?
The complete process involves two centers with differentiated roles:
- Bone marrow harvest: performed at Centro Médico Teknon (Barcelona), home of ITRT, through a guided percutaneous procedure.
- Cell culture and expansion: the sample is transported to the Institute of Molecular Biology and Genetics (IBGM, University of Valladolid and CSIC), where mesenchymal cells are isolated and expanded in a cleanroom under GMP standards, with cell characterization and batch-by-batch quality controls.
- Administration and follow-up: the cell-based medicinal product is transported back to Teknon, where it is administered to the patient and clinical and MRI follow-up is carried out.
Each batch is released with its quality certificate and is administered only with the individual AEMPS authorization issued for that specific patient.
Legal disclaimer
Advanced therapy medicinal products with cultured mesenchymal cells (CMC) require a medical prescription and individual authorization by the AEMPS. This content is for informational purposes only and does not substitute medical advice. The clinical results mentioned correspond to patients treated in the context of authorized clinical trials and are not extrapolatable to other patients.
