Microfragmented Adipose Tissue and Its Initial Application in Articular Disease
Osteoarthritis (OA) is a degenerative disease primarily affecting articular cartilage, with joint pain being its most prominent clinical manifestation. In China, the morbidity of symptomatic OA, characterized by a knee Kellgren and Lawrence score of ≥2 accompanied by knee pain, is reported to be 8.1%. As the population ages, the incidence of OA is on the rise. Articular cartilage lacks blood vessels, nerves, and lymph, resulting in poor self-healing capabilities. Current nonsurgical treatments include medications such as non-steroidal anti-inflammatory drugs, glucocorticoids, and opioids, as well as physiotherapy treatments like hyaluronic acid (HA) or platelet-rich plasma (PRP) injections. While these methods can temporarily alleviate pain and improve joint function, they fail to halt the degeneration of articular cartilage.
Microfragmented adipose tissue (MAT) has emerged as a promising alternative for treating OA. MAT is obtained by extracting fat from the human body using a liposuction device and then processing it through an isolation and washing system without the use of digestive enzymes. This method preserves the three-dimensional scaffolds, growth factors, and cellular colonies, including mesenchymal stem cells (MSCs). MAT injections have shown potential in reducing pain, improving joint function, and avoiding adverse events in patients with OA.
Mechanism of MAT
MAT is collected through a simple and safe procedure that does not require digestive enzymes or additives. Patients typically choose fat-rich areas such as the lower or lateral abdomen as donor sites. After local anesthesia is administered, Klein solution is injected into the selected area via a hypodermic injection. A small skin incision of approximately 2 to 3 mm is made, and around 60 mL of adipose tissue is manually extracted using an injector connected to a disposable liposuction intubation. The MAT preparation tool is a closed cylindrical system filled with 0.9% NaCl solution and is free of air. The adipose tissue is placed into a barrel by a blue filter and shaken for about 1 minute to emulsify it. During shaking, a flow of 0.9% NaCl solution is maintained to eliminate blood elements and residues associated with adipose tissue emulsification. When the fluid becomes clear, the floating MAT is collected using a gray filter outlet connected to an injector under the device. Approximately 20 to 30 mL of MAT can be collected from 60 mL of adipose tissue. Throughout this process, the adipose tissue encounters only slight mechanical force, preserving the interstitial vascular niche and the integrity of the tissue itself.
Recent studies have demonstrated that adipose tissue contains multi-lineage progenitor cells that function as MSCs. These MSCs can be isolated from the stromal vascular fraction (SVF) obtained through enzymatic digestion of adipose tissue. However, MAT retains more pericytes and fewer adventitial stromal cells compared to SVF, indicating that the perivascular niche remains intact. Pericytes, which surround capillaries and microvessels, and adventitial stromal cells, which surround arteries and veins, have been identified as progenitor cells in vitro. Both pericytes and adventitial cells express MSC markers in vivo and can promote mesodermal differentiation upon culture. Transcriptomic analysis of single pericytes purified from human adipose tissue has confirmed the presence of progenitor cells and revealed that adventitial stromal cells may be more primitive than pericytes in development.
Quantitative studies using laser flow cytometry have shown that MAT retains more pericytes but fewer adventitial stromal cells, suggesting that arteries and veins surrounded by the adventitia are lost after mechanical dissociation, while microvessels persist in MAT. Immunofluorescence for pericyte markers has shown that pericytes expressing NG2 or platelet-derived growth factor receptor-b (PDGFR-b) are resistant and function as peri-endothelial cells in microvessels after mechanical segmentation, proving that the perivascular niche is preserved intact. Additionally, pericytes can participate in tissue repair through the secretion of growth factors and cytokines. MAT contains more angiogenic growth factors, such as angiogenin, endoglin, dipeptidyl peptidase IV, hepatocyte growth factor, and placenta growth factor, as well as cytokines like adiponectin, CD14, CD31, insulin-like growth factor binding protein 2, and complement D. These secretions not only aid in tissue repair but also have anti-inflammatory effects. In mice with sepsis, inflammation was significantly reduced after MAT injection. Comparative studies have shown that MAT maintains the secretion of active cytokines for 28 days, while the MSC contents and cytokine activity from syngeneic adipose tissue decrease rapidly within a week. MAT medium can reduce the migration of U937 monocytes at the early stage and persist in its effect after 14 days, whereas adipose tissue loses its effect. In summary, MAT maintains the intact stromal vascular niche, aids in repairing damaged areas, and reduces inflammatory responses through the secretory ability of the niches.
Animal Model Exploration
Animal models have been used to explore the mechanism and indications of MAT. Researchers have identified that MAT can be used to treat cartilage damage. Since articular cartilage lacks blood vessels and material transport mainly depends on diffusion, it is feasible to repair cartilage through MAT injection. To evaluate the safety, feasibility, and clinical effects of MAT injection into articular cartilage, a study was conducted on 130 dogs with spontaneous OA. The dogs received a single joint MAT injection, and follow-up was performed at 2 weeks, 1 month, 3 months, and 6 months after treatment. Assessments included radiographic results, the Helsinki chronic pain index (HCPI), and a modified orthopedic score (OS) that evaluates lameness. The OS results showed that 88% of dogs improved within 6 months, 11% showed no changes, and 1% deteriorated. The HCPI results demonstrated that 63% of dogs were apparently improved within 6 months, 29% were obviously improved, 6% were slightly improved, and 2% deteriorated. Radiographic results of dogs with improved conditions showed that cartilage lesions were filled, and joint fluid was slightly reduced. No treatment-related complications were observed. The reduction in pain and decreased dysfunction observed with MAT injection was similar to the experimental results from PRP injection. However, since PRP requires multiple injections while MAT only requires one injection to promote long-term effects, further comparative studies of MAT, HA, and PRP are necessary.
Initial Clinical Application
MAT has also been applied in clinical settings to treat various articular diseases. In a study involving 20 subjects with chronic shoulder pain and rotator cuff injuries, MAT injection was performed. Each subject had a history of chronic shoulder pain for more than one year and could not raise their arms above 90°. Follow-up was conducted at the 1st and 5th weeks and the 3rd, 6th, and 12th months after injection. Assessments included the numerical pain scale (NPS) and the American Shoulder and Elbow Surgeons Score (ASES). The NPS improved significantly after treatment compared to the baseline and continued to benefit the patients over the next 12 months. The ASES improved linearly in the first three months and continued to benefit the patients throughout the entire 12 months. No adverse events were reported during the follow-up period. The absence of adverse events may be attributed to the anti-inflammatory cytokines in MAT, the filtration of substances associated with inflammatory reactions during MAT preparation, and the use of the patient’s own adipose tissue, which does not trigger an immune response.
In another case, a 59-year-old male patient with severe knee pain, OA, a medial meniscus tear, and patellomalacia received a MAT injection. Approximately six months after the injection, his Visual Analog Scale (VAS) score improved from 8 to 0, and MRI showed that the articular cartilage had expanded the joint space from 0.75 to 1.50 mm. The MRI results indicated that MAT could provide support, buffer, and fill soft tissue, demonstrating a latent healing ability.
A long-term follow-up study was conducted on a 33-year-old man with knee injuries from a skiing accident. The patient underwent microfracture surgery and anterior cruciate ligament reconstruction but continued to experience persistent knee pain. After receiving a MAT injection, the patient’s pain improved within 10 days and disappeared completely by the 6th week. The clinical situation remained stable at the 12th and 30th months, with the patient able to perform physical activities without limitations. This case report highlights the long-term effectiveness of MAT injection in reducing pain and restoring joint function.
In a larger study, 38 patients with knee OA received MAT injections. The patients had knee cartilage disease grade > II (International Cartilage Research Society classification), persistent knee pain, and had failed previous treatments including HA and PRP injections and hormone therapy. The patients underwent normative arthroscopic cartilage curettage and received MAT injections, with 14 patients also receiving meniscectomy. Follow-up assessments at 1, 3, 6, and 12 months post-surgery showed that 92% of the patients improved, and 100% were satisfied with the treatment. No adverse reactions or complications were reported during follow-up. The study demonstrated the safety and effectiveness of MAT injection, even in patients who had undergone meniscectomy, which is known to accelerate OA tendencies.
Conclusions
MAT injection is an innovative technology that has been certified by the Food and Drug Administration (FDA) in the United States, Conformite Europeenne (CE) Mark in Europe, and the Therapeutic Goods Administration in Australia. It is a simple, cost-effective, and safe treatment that can achieve significant effectiveness with just one injection. Numerous basic studies and clinical trials are currently underway to explore the potential of MAT injections in treating articular cartilage injuries. Follow-up results, including unpublished data, indicate that MAT injection can reduce pain, improve joint function, and does not cause adverse events. Even in patients who have undergone multiple failed treatments, MAT injection has shown apparent pain reduction. However, the mechanism by which MSCs and their cytokines interact with chondrocytes remains unclear. The number of subjects in clinical trials is small, the treatment assessment system is not uniform, and the follow-up time is too short to observe long-term effects. Additionally, the lack of control trials makes it difficult to persuade practitioners to adopt MAT as a treatment option. Longer-term follow-up and increased randomized controlled trials are needed to provide clearer conclusions and establish MAT injection as a new non-operative orthopedic treatment option.
doi.org/10.1097/CM9.0000000000000518
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