Abstract

Fracture non-union is a challenging orthopaedic issue and a socio-economic global burden. Several biological therapies have been introduced to improve traditional surgical approaches. Among these, the latest research has been focusing on adipose tissue as a powerful source of mesenchymal stromal cells, namely, adipose-derived stem cells (ADSCs). ADSC are commonly isolated from the stromal vascular fraction (SVF) of liposuctioned hypodermal adipose tissue, and their applications have been widely investigated in many fields, including non-union fractures among musculoskeletal disorders. This review aims at providing a comprehensive update of the literature on clinical application of ADSCs for the treatment of non-unions in humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Only three articles met our inclusion criteria, with a total of 12 cases analyzed for demographics and harvesting, potential manufacturing and implantation of ADSCs. The review of the literature suggests that adipose derived cell therapy can represent a promising alternative in bone regenerative medicine for the enhancement of non-unions and bone defects. The low number of manuscripts reporting ADSC-based therapies for long bone fracture healing suggests some critical issues that are discussed in this review. Nevertheless, further investigations on human ADSC therapies are needed to improve the knowledge on their translational potential and to possibly achieve a consensus on their use for such applications.

Highlights

  • Biological therapies have been introduced, such as platelet-rich plasma (PRP), bone morphogenetic proteins (BMPs) and autologous mesenchymal stromal cells isolated from bone marrow (MSCs) [6,7]

  • A significant amount of data from basic and translational research suggests that adipose-derived stem cells (ADSCs)/stromal vascular fraction (SVF) grafting and implantation is a promising strategy for bone regeneration

  • Current literature demonstrates that clinical application of SVF and ADSCs-derived grafts is safe and feasible though it cannot be routinely performed, as it requires experienced stem cells good manufacturing practices (GMPs) manufacturing laboratories

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Summary

Introduction

Bone fractures are the most common traumatic injuries affecting large organs in humans. The limited yield of endogenous stem cells, with the secreted bioactive signals derived thereof, in autologous bone, especially in the elderly or in selected comorbidities, makes the autograft often fail to promote a functional and biologically effective bone healing. To address this criticality, biological therapies have been introduced, such as platelet-rich plasma (PRP), bone morphogenetic proteins (BMPs) and autologous mesenchymal stromal cells isolated from bone marrow (MSCs) [6,7]. ADSC are multipotent cells which can be quite isolated from the stromal vascular fraction (SVF) of liposuctioned hypodermal adipose tissue [9,10] Their applications in musculoskeletal disorders have been widely investigated, especially for cartilage and tendon regeneration [11–13]. The aim of the study is to provide an up-to-date review of the literature on the clinical application of adipose-derived stem cells for the treatment of non-unions in humans

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