• Cell therapy
• Immunomodulatory function
• Mesenchymal stromal cells
• Neuroinflammation
• Three-dimensional culture

• light‐emitting diode
• mesenchymal stem cells
• photobiomodulation

• Mesenchymal Stem Cells/radiation effects
• Mesenchymal Stem Cells/metabolism
• Mesenchymal Stem Cells/cytology
• Light
• Adipose Tissue/cytology
• Humans
• Vascular Endothelial Growth Factor A/metabolism
• Oxidative Stress/radiation effects
• Interleukin-6/metabolism
• Cells, Cultured
• Time Factors
• Red Light

• 306385/2020-1 Conselho Nacional de Desenvolvimento Científico e Tecnológico
• 2020/12547-8 Fundação de Amparo à Pesquisa do Estado de São Paulo

• Humans
• Platelet-Rich Plasma
• Osteoarthritis, Knee/therapy
• Adipose Tissue/transplantation
• Randomized Controlled Trials as Topic

• adipose tissue
• knee
• micro-fragmented adipose tissue
• minimally manipulated
• osteoarthritis
• platelet-rich plasma

• GR-2021-12374140 Italian Ministry of Health

• 3D bioprinting
• adipose tissue
• allogenic hyaline cartilage
• articular cartilage
• knee
• osteoarthritis

• adipose-derived mesenchymal stem cells
• adipose-derived mesenchymal stem cells conditioned medium
• knee osteoarthritis
• mouse model
• post-traumatic osteoarthritis

Platelet-rich plasma (PRP) has been established as safe and effective for knee osteoarthritis (OA). Another orthobiologic therapy, microfragmented adipose tissue (MFAT), has gained attention because of its heterogeneous cell population (including mesenchymal stem cells). However, prospective comparative data on MFAT are lacking. Because of the safety, efficacy, and simplicity of PRP, new therapeutics such as MFAT should be compared directly with PRP.

To compare patient-reported outcomes of a single injection of PRP versus MFAT for knee OA.

Randomized controlled trial; Level of evidence, 2.

A total of 58 patients with symptomatic knee OA (Kellgren-Lawrence grades 1-4) were randomized to receive a single injection of either leukocyte-rich PRP or MFAT under ultrasound guidance. PRP was created by processing 156 mL of whole blood. MFAT was created by harvesting 30 mL of adipose tissue via standard lipoaspiration. Scores for the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales and visual analog scale for pain with Activities of Daily Living (VAS-ADL) were recorded at baseline and at 1, 3, and 6 months after the injection. The primary outcome was the KOOS–Pain subscore at 6 months after the injection.

The PRP group (n = 30) had a mean volume of 5.12 ± 1.12 mL injected. This consisted of a mean platelet count of 2673.72 ± 1139.04 × 10³/µL and mean leukocyte count of 25.36 ± 13.27 × 10³/µL (67.81% lymphocytes, 18.66% monocytes, and 12.33% neutrophils). The MFAT group (n = 28) had a mean volume of 7.92 ± 3.87 mL injected. The mean total nucleated cell count was 3.56 ± 4.62 million/mL. In both groups, KOOS subscale and VAS-ADL scores improved from baseline, and there was no significant difference between the PRP and MFAT groups in the final KOOS–Pain subscore (80.38 ± 16.07 vs 81.61 ± 16.37, respectively; P = .67) or any other outcome score.

A single injection of either PRP or MFAT resulted in a clinically meaningful improvement for patients with knee OA at 6 months, with no difference between treatment groups.

NCT04351087 (ClinicalTrials.gov identifier).

• knee osteoarthritis
• mesenchymal stem cell
• microfragmented adipose tissue
• platelet-rich plasma

An early resolution of osteoarthritis (OA), through minimally invasive orthobiological solutions, would be important to enable a return to daily and sport activities, and delay prosthesis solutions. No study has yet evaluated amniotic epithelial stem cells (AECs) in OA. They could be considered a valid alternative to adipose derived cells, expanded or concentrated, because they differentiate into three lineages and express mesenchymal and embryonic markers, without a tumorigenic phenotype. The innovative aspects of this study are the comparison of three injective orthobiological treatments, the in vivo use of AECs in OA, and the evaluation of structural and inflammatory fronts of OA for up to six months.

The challenge of osteoarthritis (OA) is to find a minimally invasive orthobiological therapy to contrast OA progression, on inflammatory and structural fronts. The aim of the present study is to compare the effects of an intra-articular injection of three orthobiological treatments, autologous culture expanded adipose-derived mesenchymal stromal cells (ADSCs), autologous stromal vascular fraction (SVF) and allogenic culture expanded amniotic epithelial stem cells (AECs), in an animal model of OA. OA was induced in 24 sheep by bilateral lateral meniscectomy and, at 3 and 6 months post-treatment, the results were analyzed with macroscopy, histology, histomorphometry, and biochemistry. All the three treatments showed better results than control (injection of NaCl), but SVF and AECs showed superiority over ADSCs, because they induced higher cartilage regeneration and lower inflammation. SVF showed better results than AECs at 3 and 6 months. To conclude, SVF seems to be more favorable than the other biological options, because it is easily obtained and rapidly used after harvesting, with good healing potential. AECs cause no discomfort and could be also considered for the treatment of OA joints.

• animal model
• biological treatment
• meniscectomy
• osteoarthritis
• sheep

• ACL reconstruction
• ACL repair
• biologics
• platelet-rich plasma
• stem cells

Among degenerative musculoskeletal disorders, osteoarthritis remains one of the main causes of pain and disability in the adult population. Current available alternatives to alleviate symptoms include conservative treatments such as physical therapy, anti-inflammatory drugs and an educational approach to lifestyle modification. The use of certain analgesics, such as opiates and corticosteroids offer short-term results but does not address the etiological source of pain and disability. In addition, prolonged use of such medications can cause additional complications. Therefore, the demand for regeneration of joint cartilage has led to an alternative approach called "orthobiologics". This alternative is based on cellular and molecular components capable of inducing and promoting tissue repair. Products derived from adipose tissue have been studied as an excellent source of orthobiologics in an attempt to promote joint cartilage repair. However, the lack of standardization regarding collection and processing protocols presents a challenge for the generalization of study results and determination of effectiveness. To the best of our knowledge, orthobiologics derived from fat have not yet been classified. Therefore, this manuscript proposes the HGS classification system which aims to describe certain parameters that are relevant to the quality of organic products regarding harvesting techniques (H), graft type (G), and number of centrifugations (S). The more parameters used would imply greater characterization and complexity of the evaluation of the biological product used. The HGS classification may provide a valuable contribution to the understanding of clinical procedures and research results, aiming to ultimately usher in a standardization of optimal practice.

• Orthobiologics
• Adipose tissue
• Mesenchymal stem cells
• Regenerative medicine
• Musculoskeletal disorders
• Orthopedics

There has been considerable advancement over the last few years in the treatment of osteoarthritis, common chronic disease and a major cause of disability in older adults. In this pathology, the entire joint is involved and the regeneration of articular cartilage still remains one of the main challenges, particularly in an actively inflammatory environment. The recent strategies for osteoarthritis treatment are based on the use of different therapeutic solutions such as cell and gene therapies and tissue engineering. In this review, we provide an overview of current regenerative strategies highlighting the pros and cons, challenges and opportunities, and we try to identify areas where future work should be focused in order to advance this field.

• cartilage
• cell-based therapy
• gene therapy
• osteoarthritis
• tissue-based therapy

• bone regeneration
• bone turnover marker
• mesenchymal stromal cells