Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart

Polančec, Denis; Zenić, Lucija; Hudetz, Damir; Borić, Igor; Jeleč, Željko; Rod, Eduard; Vrdoljak, Trpimir; Skelin, Andrea; Plečko, Mihovil; Turkalj, Mirjana; Nogalo, Boro; Primorac, Dragan

doi:10.3390/genes10060474

Cited by 34 publications

(34 citation statements)

References 37 publications

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“…We used the pairwise t-test for paired and subsequent measurements of the same patient or a knee. Within-individual variation was defined on the basis of the dGEMRIC error rates, which were based on previously published papers, and this indicated that the mean difference per region of interest between the two T1Gd measurements ranged from 3.7% to 6.8% [14,16,18]. Based on this, we defined the arbitrary change of 15% in subsequent measurements as clinically relevant, and considered this as the liminal value (on the basis of two standard deviations from the estimated error rate).…”

Section: Discussionmentioning

confidence: 99%

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A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

Borić

Hudetz

Rod

et al. 2019

Genes

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Osteoarthritis (OA) is a widely prevalent disease worldwide, and with an increasingly ageing society, it has become a challenge for the field of regenerative medicine. OA is a disease process involving multiple joint tissues, including those not visible on radiography, and is a complex disease process with multiple phenotypes that require evaluation by a multimodality imaging assessment. The purpose of this study was to evaluate the effect of micro-fragmented fat tissue intra-articular injection 24 months after application in two ways: Indirectly using functional magnetic resonance imaging (MRI) assessment analyzing the glycosaminoglycans (GAG) content in cartilage by means of delayed gadolinium (Gd)-enhanced magnetic resonance imaging of cartilage (dGEMRIC), as well as clinical outcome on observed level of GAG using standard orthopedic physical examination including VAS assessment. In our previous study assessing comprehensive results after 12 months, the dGEMRIC results have drawn attention. The present study explores the long-term effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2018. A total of 17 patients were enrolled in the study, and 32 knees were assessed in a 12-month follow-up, but only 10 patients of them with 18 knees are included in a 24-month follow-up. The rest of the seven patients dropped out of the study 12 months after follow-up: three patients underwent knee arthroplasty, and the remaining four did not fulfil the basic criteria of 24 months involvement in the study. Surgical intervention (lipoaspiration), followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s), was performed in all patients. Patients were assessed for a visual analog scale (VAS), dGEMRIC at the baseline, three, six, 12 and 24 months after the treatment. A magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively-charged contrast gadopentetate dimeglumine (Gd-DTPA2) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. Our results suggest that this method of single intra-articular injection of autologous microfragmented adipose tissue improves GAG content on a significant scale, with over half of the measurements suggesting relevant improvement 24 months after intra-articular injection opposed to the expected GAG decrease over the natural course of the disease.

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Section: Discussionmentioning

confidence: 99%

“…The collected and processed final microfragmented adipose tissue product was transferred to several 10 mL syringes and injected intra-articularly (4-15 mL) into the index knee. Immunophenotyping of a stromal vascular fraction from microfragmented lipoaspirate was also done [16].…”

Section: Transplantation and Processing Of Microfragmented Adipose Timentioning

confidence: 99%

A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

Borić

Hudetz

Rod

et al. 2019

Genes

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“…Another study included classifying and describing cell types contributing to the effect of treatment [ 207 ]. A stromal vascular fraction from lipoaspirate (SVF-LA) and stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) samples were characterized, and the following population phenotypes were identified within the CD45− fraction: endothelial progenitor cells (EPC), endothelial mature cells, pericytes, transitional pericytes, and supra adventitial-adipose stromal cells (SA-ASC).…”

Section: State-of-the-art Non-operative Therapeutic Considerationmentioning

confidence: 99%

Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations

Primorac

Molnar

Rod

et al. 2020

Genes

261

176

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Being the most common musculoskeletal progressive condition, osteoarthritis is an interesting target for research. It is estimated that the prevalence of knee osteoarthritis (OA) among adults 60 years of age or older is approximately 10% in men and 13% in women, making knee OA one of the leading causes of disability in elderly population. Today, we know that osteoarthritis is not a disease characterized by loss of cartilage due to mechanical loading only, but a condition that affects all of the tissues in the joint, causing detectable changes in tissue architecture, its metabolism and function. All of these changes are mediated by a complex and not yet fully researched interplay of proinflammatory and anti-inflammatory cytokines, chemokines, growth factors and adipokines, all of which can be measured in the serum, synovium and histological samples, potentially serving as biomarkers of disease stage and progression. Another key aspect of disease progression is the epigenome that regulates all the genetic expression through DNA methylation, histone modifications, and mRNA interference. A lot of work has been put into developing non-surgical treatment options to slow down the natural course of osteoarthritis to postpone, or maybe even replace extensive surgeries such as total knee arthroplasty. At the moment, biological treatments such as platelet-rich plasma, bone marrow mesenchymal stem cells and autologous microfragmented adipose tissue containing stromal vascular fraction are ordinarily used. Furthermore, the latter two mentioned cell-based treatment options seem to be the only methods so far that increase the quality of cartilage in osteoarthritis patients. Yet, in the future, gene therapy could potentially become an option for orthopedic patients. In the following review, we summarized all of the latest and most important research in basic sciences, pathogenesis, and non-operative treatment.

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“…As already underlined in our previous review, Lipogems ® is currently used within the clinic in several orthopedic contraindications, where intra-articular injections are used to for the management of knee, hip and shoulder osteoarthritic degeneration (more than 35000 patients over the world). Initiated more than three years ago, these results have now been confirmed in several case series [50,51], and prospective clinical studies with follow up [52,53], and the "regenerative" pathophysiological mechanism of Lipogems ® , when injected into the joint, have now been more carefully elucidated [54,55]. MFAT has also been demonstrated effective also in four patients with osteochondral lesions of the talus [56] who underwent to arthroscopic injection of MFAT of the osteochondral lesion after a first phase of microperforation of the cartilage.…”

Section: Orthopedic Surgerymentioning

confidence: 89%

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Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart

Cited by 34 publications

References 37 publications

A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations

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