What is it about?

Adipose tissue-derived stem cells (ASCs) in the form of stromal vascular fraction (SVF) and cultured expansion have been applied in clinical settings in some countries to treat osteoarthritis (OA) of knees, one of the most common debilitating, incurable disorders. Since the first report of successful cartilage-like tissue regeneration with autologous adipose SVF containing ASCs, there has been a gradual increase in the number of publications confirming such results. Thus far, most of the reports have been limited to treatments of OA of knees. Recently, successful applications of adipose SVF in treating OA of ankles and hips have been reported. In addition, several groups have reported modified method of applying adipose SVF, such as combining bone marrow stimulation with adipose SVF or adding additional extracellular matrix (ECM) in treating OA. Here, we present an updated, systematic review of clinical effectiveness and safety in treating OA of knees, ankles, and one hip since 2016 using ASCs in the form of adipose SVF or in cultured expansion, along with a description and suggestion of potential biological mechanisms of cartilage regeneration.

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Why is it important?

With accumulation of clinical data, potential mechanisms of actions of MSCs regenerating cartilage tissue have been postulated. Although it is not yet clear, the mechanism involves engraftment of stem cells and their trophic effects working together in harmony. MSCs secrete various bioactive factors: cytokines, growth factors, and extracellular vesicles, which include exosomes that transfer cytoplasmic contents from one cell to other recipient cells. Caplan first postulated that these bioactive factors have trophic effects, regenerating cartilage tissue via autocrine and paracrine fashions. Later, other groups provided evidence that MSCs actually attach at the site of cartilage defects and regenerate cartilage. Adipose tissue is an excellent source of MSCs. One gram of adipose tissue may yield up to 2,000,000 nucleated cells, of which 1% to 10% is considered to be ASCs. Based on these numbers, we can be certain that sufficient number of ASCs can be provided to treat OA with adequate amount of adipose tissue. Since a large number of MSCs attached at the site of injury may produce a huge quantity of trophic factors, it is only logical to assume that utilizing a great number of stem cells would produce better efficacy, as demonstrated by other groups. In such a sense, culture expansion of the stem cells may be able to produce better efficacy than autologous adipose SVF.

Perspectives

At present, there is no cure for painful OA for knees, hips, and ankles. For these patients, treatment with ASCs, either in the form of adipose SVF cells or culture-expanded cells, can be an alternative option that has been slowly gaining evidence of being safe and efficacious. As data accumulates, the mechanisms of cartilage regeneration by ASCs/MSCs are being elucidated to involve both direct engraftment and trophic factors. Among the trophic factors, extracellular vesicles, especially exosomes, are gaining much attention. ASC/MSC-based therapy, as with all other cell-based therapies, incurs significant operational efforts and costs as the therapy requires stringent manufacturing process, storage, and delivery to patients in order to ensure the safety and optimal viability of the cells. Thus, isolating the potential trophic factors responsible for cartilage regeneration may help to overcome these obstacles and possibly apply the therapy to general patient population. For now, though, better designed studies are needed to elucidate the true mechanism of the action of the therapy and possibly for general application of these stem cells to treat OA/DJD by cartilage regeneration.

Professor Sang Hee Lee
Myongji University

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This page is a summary of: Cartilage Regeneration in Humans with Adipose Tissue-Derived Stem Cells and Adipose Stromal Vascular Fraction Cells: Updated Status, International Journal of Molecular Sciences, July 2018, MDPI AG,
DOI: 10.3390/ijms19072146.
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