Introduction

Alterations in articular cartilage can produce pain and reduce the quality of life, evolving into the development of osteoarthritis (OA) and consequently permanent disabling symptoms.

Pharmacological or surgical treatments currently used for OA patients can help with the management of symptoms and delay disease progression [1–3], but metal resurfacing is the only currently available treatment able to provide pain relief and satisfactory function recovery, when the final stages of OA are reached [4–7]. Although new treatment options have come from recent achievements in biotechnologies [8, 9], the regeneration of hyaline cartilage is still a chimera [10]. Looking for a new direction in cartilage regeneration, the recent history of orthopaedics has been enriched with innovative therapies, ranging from platelet-derived growth factors (GFs) to cell-based treatments [11, 12], also combined with various biomaterials for tissue engineering strategies. In particular, recently mesenchymal stem cells (MSCs) are emerging as an alternative to the use of differentiated chondrocytes, thanks to their potential to differentiate into several lines such as osteoblasts, chondrocytes, myoblasts, or adipocytes and to their capability of self-renewal, high plasticity, and immunosuppressive and anti-inflammatory action [13]. MSCs can be obtained from different human sources, such as bone marrow, periosteum, umbilical cord blood, dermis, muscle, infrapatellar fat pad, synovial membrane, and adipose tissue [13]. Among these sources, adipose-derived mesenchymal stem cells (ADSCs) are attracting attention as an alternative to the better studied bone marrow mesenchymal stem cells (BMSCs) [14, 15]. The reasons for increased interest in ADSCs reside in their abundance (ADSCs are 5% of nucleated cells versus 0.0001–0.01% of BMSCs), the ease with which they can be harvested (with the advantages of lower donor-site morbidity), and their rapid expansion and high proliferation potential [16]; moreover, they have shown that they can maintain their phenotype better over many culture passages with respect to BMSCs [17]. Thus, over the last decade, the number of preclinical and clinical papers dealing with ADSCs has increased significantly. However, their mechanism of action is not fully understood, since both the differentiation of stem cells by themselves and paracrine and trophic effects might be involved. Moreover, the optimal strategy for applying ADSCs has not yet been identified and many aspects still remain controversial [18].

The aim of this systematic review is to analyze the current literature on the use of ADSCs in vivo to show the available evidence on their therapeutic potential for cartilage regeneration, by investigating their efficacy, drawbacks, and possible future application strategies in humans for the treatment of chondral pathologies.

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