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Journal ArticleDOI

Patients with stage II of the knee osteoarthritis most likely benefit from the intra-articular injections of autologous adipose tissue—from 2 years of follow-up studies

TL;DR: In this paper, the authors defined a specific group of patients with knee osteoarthritis, who are the most likely to benefit from the treatment with intra-articular injection of an autologous adipose tissue (AAT).
Abstract: Knee osteoarthritis (OA) is a common, chronic, progressive and degenerative disease which affects patients’ quality of life and may cause disability and social isolation. OA is a huge economic burden for the patient and a large strain for the whole healthcare system. Articular cartilage has a small potential to repair, with progressively more clinicians emphasizing cellular therapy. Subcutaneous fat tissue in human body is a large reservoir of mesenchymal stem cells (MSCs) and is been harvested in minimally invasive, simple procedure. The purpose of this study was to define a specific group of patients with knee osteoarthritis, who are the most likely to benefit from the treatment with intra-articular injection of an autologous adipose tissue (AAT). From 2016 to 2018, 59 symptomatic bilateral and unilateral knee OA patients were treated with a single intra-articular (IA) injection of an autologous adipose tissue (AAT). Before the treatment and at the follow-up, the participant was asked to fulfill the Knee Injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee 2000 (IKDC 2000), The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Health Questionnaire EQ-5D-5L and to quantify the pain in the affected joint with a Numeric Rating Scale (NRS). Moreover, the patients were asked to: (i) assess their satisfaction with the effects of the conducted treatment: from 0 (unsatisfied) to 10 (very satisfied), (ii) describe the rehabilitation, if it was performed (supervised or individual and duration in weeks) and (iii) indicate any additional treatment applied, like IA injections of hyaluronic acid (HA) or platelet-rich plasma (PRP), knee arthroscopy, partial or total knee arthroplasty (TKA) at the follow-up. The mean age of 37 participants (16 males and 21 females) included into statistical analysis was 57.78 ± 7.39 years, the mean BMI was 31.30 ± 7.51. The questionnaires were fulfilled after the average follow-up time of 27 ± 6.5 months. A significant difference (p < 0.05) compared with the baseline, was observed in pain [NRS], WOMAC, KOOS index, pain, symptoms, ADL, Sport and Rec, QoL, EQ-5D-5L index. The satisfaction in the whole group was 6.16 ± 3.07. There was no significant difference between satisfied and unsatisfied patients in BMI and pain [NRS] at the baseline. 6 out of 7 patients with stage IV in K-L were unsatisfied with the effects of the treatment with AAT. The main conclusion of this study is that the patients with stage II of the knee OA with normal BMI are were most likely to benefit from IA injection of AAT, in contrast to the patients with stage IV, who will not beware not satisfied with the effectiveness of this kind of treatment. There were no adverse events reported at the donor site as well as in the treated knee joints.

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Journal ArticleDOI
09 Feb 2022-Cells
TL;DR: Clinicians should interpret the results of the 19 assessed meta-analyses of clinical studies on the management of primary knee osteoarthritis with stem cells with caution and should be cautious of the conclusions drawn therein.
Abstract: (1) Background: Conclusions of meta-analyses of clinical studies may substantially influence opinions of prospective patients and stakeholders in healthcare. Nineteen meta-analyses of clinical studies on the management of primary knee osteoarthritis (pkOA) with stem cells, published between January 2020 and July 2021, came to inconsistent conclusions regarding the efficacy of this treatment modality. It is possible that a separate meta-analysis based on an independent, systematic assessment of clinical studies on the management of pkOA with stem cells may reach a different conclusion. (2) Methods: PubMed, Web of Science, and the Cochrane Library were systematically searched for clinical studies and meta-analyses of clinical studies on the management of pkOA with stem cells. All clinical studies and meta-analyses identified were evaluated in detail, as were all sub-analyses included in the meta-analyses. (3) Results: The inconsistent conclusions regarding the efficacy of treating pkOA with stem cells in the 19 assessed meta-analyses were most probably based on substantial differences in literature search strategies among different authors, misconceptions about meta-analyses themselves, and misconceptions about the comparability of different types of stem cells with regard to their safety and regenerative potential. An independent, systematic review of the literature yielded a total of 183 studies, of which 33 were randomized clinical trials, including a total of 6860 patients with pkOA. However, it was not possible to perform a scientifically sound meta-analysis. (4) Conclusions: Clinicians should interpret the results of the 19 assessed meta-analyses of clinical studies on the management of pkOA with stem cells with caution and should be cautious of the conclusions drawn therein. Clinicians and researchers should strive to participate in FDA and/or EMA reviewed and approved clinical trials to provide clinically and statistically valid efficacy.

5 citations

Journal ArticleDOI
TL;DR: In this paper , a review of the regulatory landscape governing the utilization of autologous and allogeneic adipose tissue remains complex, and the FDA's nomenclature and guidance regarding adipose products are discussed.
Abstract: Adipose tissue is widely recognized as an abundant and accessible human tissue that serves as a source of cells and extracellular matrix scaffolds for regenerative surgical applications. Increasingly, orthopedic surgeons are turning to adipose tissue as a resource in their treatment of osteoarthritis and related conditions. In the U.S., the regulatory landscape governing the orthopedic surgical utilization of autologous and allogeneic adipose tissue remains complex. This manuscript reviews the Food and Drug Administration's nomenclature and guidance regarding adipose tissue products. Additionally, it surveys recent pre-clinical and clinical trial literature relating to the application of adipose-derived cells and tissues in the treatment of osteoarthritis.

4 citations

Journal ArticleDOI
TL;DR: The meta-analysis of clinical research shows that intra-articular injection of SVF, in combination with adjuvant surgery, could alleviate pain and improve early functional recovery for patients with KDJD at Kellgren-Lawrence (KL) grades II–III.

1 citations

Journal ArticleDOI
TL;DR: The role of a combination therapy with use of intra-articular corticosteroids is lacking in the absence of adequate study data and cannot be defined yet as discussed by the authors , however, the current scientific data do not yet justify any recommendation for its use.
Abstract: Guideline-based surgical cartilage therapy for focal cartilage damage offers highly effective possibilities to sustainably reduce patients' complaints and to prevent or at least delay the development of early osteoarthritis. In the knee joint, it has the potential to reduce almost a quarter of the arthroses requiring joint replacement caused by cartilage damage. Biologically effective injection therapies could further improve these results. Based on the currently available literature and preclinical studies, intra- and postoperative injectables may have a positive effect of platelet-rich plasma/fibrin (PRP/PRF) and hyaluronic acid (HA) on cartilage regeneration and, in the case of HA injections, also on the clinical outcome can be assumed. The role of a combination therapy with use of intra-articular corticosteroids is lacking in the absence of adequate study data and cannot be defined yet. With regard to adipose tissue-based cell therapy, the current scientific data do not yet justify any recommendation for its use. Further studies also regarding application intervals, timing and differences in different joints are required.
References
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Journal ArticleDOI
TL;DR: The burden of four major musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, osteoporosis, and low back pain, which affects nearly everyone at some point in time and about 4-33% of the population at any given point is described.
Abstract: Musculoskeletal conditions are a major burden on individuals, health systems, and social care systems, with indirect costs being predominant. This burden has been recognized by the United Nations and WHO, by endorsing the Bone and Joint Decade 2000-2010. This paper describes the burden of four major musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, osteoporosis, and low back pain. Osteoarthritis, which is characterized by loss of joint cartilage that leads to pain and loss of function primarily in the knees and hips, affects 9.6% of men and 18% of women aged > 60 years. Increases in life expectancy and ageing populations are expected to make osteoarthritis the fourth leading cause of disability by the year 2020. Joint replacement surgery, where available, provides effective relief. Rheumatoid arthritis is an inflammatory condition that usually affects multiple joints. It affects 0.3-1.0% of the general population and is more prevalent among women and in developed countries. Persistent inflammation leads to joint destruction, but the disease can be controlled with drugs. The incidence may be on the decline, but the increase in the number of older people in some regions makes it difficult to estimate future prevalence. Osteoporosis, which is characterized by low bone mass and microarchitectural deterioration, is a major risk factor for fractures of the hip, vertebrae, and distal forearm. Hip fracture is the most detrimental fracture, being associated with 20% mortality and 50% permanent loss in function. Low back pain is the most prevalent of musculoskeletal conditions; it affects nearly everyone at some point in time and about 4-33% of the population at any given point. Cultural factors greatly influence the prevalence and prognosis of low back pain.

3,361 citations

Journal ArticleDOI
TL;DR: Evidence that leads to the proposal that during local injury, MSCs are released from their perivascular location, become activated, and establish a regenerative microenvironment by secreting bioactive molecules and regulating the local immune response is discussed.

1,402 citations

Journal ArticleDOI
TL;DR: The integrated in vivoframework presented here will be helpful for the interpretation of laboratory experiments as well as for the development of new methods for the evaluation of OA at the knee.
Abstract: The in vivo pathomechanics of osteoarthritis (OA) at the knee is described in a framework that is based on an analysis of studies describing assays of biomarkers, cartilage morphology, and human function (gait analysis). The framework is divided into an Initiation Phase and a Progression Phase. The Initiation Phase is associated with kinematic changes that shift load bearing to infrequently loaded regions of the cartilage that cannot accommodate the loads. The Progression Phase is defined following cartilage breakdown. During the Progression Phase, the disease progresses more rapidly with increased load. While this framework was developed from an analysis of in vivo pathomechanics, it also explains how the convergence of biological, morphological, and neuromuscular changes to the musculoskeletal system during aging or during menopause lead to the increased rate of idiopathic OA with aging. Understanding the in vivo response of articular cartilage to its physical environment requires an integrated view of the problem that considers functional, anatomical, and biological interactions. The integrated in vivo framework presented here will be helpful for the interpretation of laboratory experiments as well as for the development of new methods for the evaluation of OA at the knee.

961 citations

Journal ArticleDOI
TL;DR: The name of MSCs should be changed to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning thatThese cells make therapeutic drugs in situ that are medicinal.
Abstract: Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to represent a class of cells from human and mammalian bone marrow and periosteum that could be isolated and expanded in culture while maintaining their in vitro capacity to be induced to form a variety of mesodermal phenotypes and tissues. The in vitro capacity to form bone, cartilage, fat, etc., became an assay for identifying this class of multipotent cells and around which several companies were formed in the 1990s to medically exploit the regenerative capabilities of MSCs. Today, there are hundreds of clinics and hundreds of clinical trials using human MSCs with very few, if any, focusing on the in vitro multipotential capacities of these cells. Unfortunately, the fact that MSCs are called "stem cells" is being used to infer that patients will receive direct medical benefit, because they imagine that these cells will differentiate into regenerating tissue-producing cells. Such a stem cell treatment will presumably cure the patient of their medically relevant difficulties ranging from osteoarthritic (bone-on-bone) knees to various neurological maladies including dementia. I now urge that we change the name of MSCs to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning that these cells make therapeutic drugs in situ that are medicinal. It is, indeed, the patient's own site-specific and tissue-specific resident stem cells that construct the new tissue as stimulated by the bioactive factors secreted by the exogenously supplied MSCs. Stem Cells Translational Medicine 2017;6:1445-1451.

709 citations

Journal ArticleDOI
TL;DR: A subpopulation of human perivascular cells that express both pericyte and mesenchymal stem cell (MSC) markers in situ is document, establishing that MSCs found throughout fetal and adult tissues are members of thepericyte family of cells.

647 citations

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