The objective of this study was to compare the clinical efficacy of repeated doses of leucocyte-poor platelet-rich plasma (LP-PRP) plus hyaluronic acid (HA) to a single dose of autologous microfrag...

A Prospective Study Comparing Leukocyte-Poor Platelet-Rich Plasma Combined with Hyaluronic Acid and Autologous Microfragmented Adipose Tissue in Patients with Early Knee Osteoarthritis.

Introduction Over the past decade, human adipose-derived mesenchymal stem/signaling/stromal cell (ADSC) therapies have become increasingly popular as a biologic treatment for a variety of orthopedic conditions. ADSCs represent a source of stromal cells with biologic properties that allow for paracrine and immunomodulatory functions and the ability to differentiate into various downstream cellular tissues. Before considering the use of adipose tissue as a cellular source, it is imperative to understand its anatomy and physiology and its roles in the human body. Objectives To review the current literature regarding the anatomy, physiology, and various roles of human adipose tissue, as well as harvesting techniques and its role in biologic therapy. Methods A comprehensive literature review that included searches of PubMed, medline, EMBASE, and Google Scholar database(s), including both preclinical and clinical studies, was performed. Results This manuscript represents an updated understanding of adipose tissue, including its anatomy, functions in the human body, and role as a perivascular cellular source for tissue renewal, in addition to its role in providing cushioning and support to various structures. Conclusion Adipose tissue is widespread throughout the body and serves multiple physiologic functions. It can be harvested through several techniques and is an abundant source of bioactive molecules and ADSCs. Research in orthopedic surgery has begun using adipose tissue as a source of homologous and non-homologous cell and tissue applications. Future study will continue to investigate optimal sources of adipose-derived cells and tissues, and its therapeutic applications in orthopedics.

The essential roles of human adipose tissue: Metabolic, thermoregulatory, cellular, and paracrine effects

With the insufficient satisfaction rates and high cost of operative treatment for osteoarthritis (OA), alternatives have been sought. Furthermore, the inability of current medications to arrest disease progression has led to rapidly growing clinical research relating to mesenchymal stem cells (MSCs). The availability and function of MSCs vary according to tissue source. The three primary sources include the placenta, bone marrow, and adipose tissue, all of which offer excellent safety profiles. The primary mechanisms of action are trophic and immunomodulatory effects, which prevent the further degradation of joints. However, the function and degree to which benefits are observed vary significantly based on the exosomes secreted by MSCs. Paracrine and autocrine mechanisms prevent cell apoptosis and tissue fibrosis, initiate angiogenesis, and stimulate mitosis via growth factors. MSCs have even been shown to exhibit antimicrobial effects. Clinical results incorporating clinical scores and objective radiological imaging have been promising, but a lack of standardization in isolating MSCs prevents their incorporation in current guidelines.

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Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review

Background Knee osteoarthritis (KOA) is a significant cause of disability in a globally ageing population. Knee replacement surgery has been shown to improve function and quality of life. Access to this intervention can be limited for a number of reasons including rationing of care, lack of healthcare provision in austere environments, and more recently, due to the cessation of elective orthopaedic care as a result of the COVID pandemic. Referral for knee replacement surgery is often guided by the patient's Oxford Knee Score (OKS). Recent therapies including treatment with microfragmented adipose tissue (MFAT) have emerged as alternatives to relieve pain and improve function in such patients. Method We identified all patients with KOA Kellgren-Lawrence grade 3 and 4 in our dataset of patients treated with a single injection of MFAT and applied published OKS thresholds for referral for TKR to separate them into 3 cohorts according to their functional impairment. 220 patients (95 females, 125 males) with KOA were given one MFAT injection. The function (OKS) and quality of life (EuroQol-5) prior to and 24 months after therapy were compared. Results MFAT injection provided a statistically significant improvement in the quality of life (EQ-5D) at 24 months in patients with a baseline OKS of 39 or less (p value: <0.001) as well as those with OKS of 27 or less who are deemed suitable for a knee replacement (p value: <0.001). Conclusion MFAT injection improves quality of life in patients with KOA who are deemed suitable for the knee replacement. MFAT is a low-morbidity alternative biological treatment and can delay the need for total knee replacement in suitable patients.

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Microfragmented Adipose Tissue Injection (MFAT) May Be a Solution to the Rationing of Total Knee Replacement: A Prospective, Gender-Bias Mitigated, Reproducible Analysis at Two Years.

Introduction Subchondral bone pathology includes a wide range of pathologies, such as osteoarthritis, spontaneous insufficiency fractures, osteonecrosis, transient bone marrow lesions syndromes, and trauma. They show typical magnetic resonance imaging (MRI) findings termed bone marrow lesions (BMLs). However, the etiology and evolution of BMLs in multiple conditions remains unclear. There is still no gold standard treatment protocol in treating BMLs in the knee, and a variety of treatment modalities have been tested in the hope that they might reduce pain and stop disease progression. Objectives To review the treatment options for BMLs of the knee. Methods A literature review was performed that included searches of PubMed, Cochrane, and Medline databases using the following keywords: Bone marrow lesions, sub chondroplasty, bone marrow concentrate, platelet-rich plasma (PRP), subchondral bone augmentation. Results The use of novel biologic techniques to treat BMLs in the knee, such as PRP and Bone Marrow Cells, has yielded promising clinical outcomes. Conclusions Future research of BMLs will be mandatory to address the different pathologies better and determining appropriate treatment strategies. There is still a need for high-quality RCTs studies and systematic reviews in the future to enhance further treatment strategy in preventing or treating BMLs of the knee.

A review of bone marrow lesions in the arthritic knee and description of a technique for treatment

The aim of this study is to evaluate the outcomes of autologous microfragmented adipose tissue (MFAT) injection in elderly patients with knee osteoarthritis (OA). We hypothesized that MFAT knee infiltration for the treatment of knee OA would yield good clinical results out to two years follow-up. Multi-centric, international, open-label study conducted by orthopedic surgery, and/or regenerative medicine facilities utilizing patient registries. Subjects recruited for eligibility. The primary outcome measure was Knee Injury and Osteoarthritis Outcome Score (KOOS). Outcomes and patient factors were compared to baseline, at six, 12, and 24 months. Statistical models were used to assess KOOS subscores and probability of exceeding the Minimally Clinically Important Difference (MCID) or Patient Acceptable Symptom State (PASS), and to assess the effect of the treatment variables on KOOS - Pain. Seventy-five patients, 120 primary treatments, mean age 69.6 years, (95%CI 68.3–70.9), BMI 28.4 (95%CI 27.3–29.6), with KL grade 2 to 4 knee OA treated with a single MFAT injection. KL grades 2 (15.1%), 3 (56.3%), and 4 (28.6%), with 20.8% of knees having previously undergone surgery. Patients with KL grade 2 disease had the best results in KOOS - Pain (P = 0.001), at six, 12, and 24 months. Including advanced KL grade 3 and 4 osteoarthritis patients, significant functional and quality of life success was seen in 106/120 treatments (88.3%, 66 patients) at all follow-up time points. Fourteen treatments (11.7%, 9 patients) failed prior to the study endpoint. This study shows that a single-dose MFAT injection leads to clinical, functional, and quality of life improvement at two years in elderly patients, in KL grades 2 to 4 of knee osteoarthritis. These findings provide evidence that this treatment modality could be a safe and effective option to other commonly available treatments in carefully selected patients.

Two-year clinical outcomes of autologous microfragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study

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Response to letter to the editor: “Remarks on Gobbi et al.: Two-year clinical outcomes of autologous micro-fragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study”

Richard D Striano

Papers

Two-year clinical outcomes of autologous microfragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study

Response to letter to the editor: “Remarks on Gobbi et al.: Two-year clinical outcomes of autologous micro-fragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study”