Adipose-Derived Stromal Cells for Chronic Wounds: Scientific Evidence and Roadmap Toward Clinical Practice

Abstract

Chronic wounds, ie, non-healing ulcers, have a prevalence of ~1% in the general population. Chronic wounds strongly affect the quality of life and generate considerable medical costs. A fraction of chronic wounds will heal within months of appropriate treatment; however, a significant fraction of patients will develop therapy-refractory chronic wounds, leading to chronic pain, infection, and amputation. Given the paucity of therapeutic options for refractory wounds, cell therapy and in particular the use of adipose-derived stromal cells (ASC) has emerged as a promising concept. ASC can be used as autologous or allogeneic cells. They can be delivered in suspension or in 3D cultures within scaffolds. ASC can be used without further processing (stromal vascular fraction of the adipose tissue) or can be expanded in vitro. ASC-derived non-cellular components, such as conditioned media or exosomes, have also been investigated. Many in vitro and preclinical studies in animals have demonstrated the ASC efficacy on wounds. ASC efficiency appears to occurs mainly through their regenerative secretome. Hitherto, the majority of clinical trials focused mainly on safety issues. However more recently, a small number of randomized, well-controlled trials provided first convincing evidences for a clinical efficacy of ASC-based chronic wound therapies in humans. This brief review summarizes the current knowledge on the mechanism of action, delivery and efficacy of ASC in chronic wound therapy. It also discusses the scientific and pharmaceutical challenges to be solved before ASC-based wound therapy enters clinical reality.

Adipose-Derived Stromal Cells within a Gelatin Matrix Acquire Enhanced Regenerative and Angiogenic Properties: A Pre-Clinical Study for Application to Chronic Wounds

“…Thus, the gelatin-based delivery studied here represents an attractive, non-invasive route, which maximizes the local efficacy of ASC therapy for chronic wound care without toxicity/tumorigenicity. The risk of side effects of ASC/gelatin therapy are considered to be limited because (i) clinical-grade gelatin is widely used in surgery worldwide (as hemostatic sponges), and (ii) ASC have been extensively studied and administrated through many delivery routes, showing an excellent tolerance in humans [ 5 ]. First-in-human studies are planned soon to clinically validate the use of the ASC-patch solution as a simple and effective treatment improving patient compliance and physician acceptance.…”

“…Even in the presence of guidelines, severe ulcers are not efficiently managed with current therapies. In this respect, cell therapy based on adipose-derived stromal cells (ASC) has emerged as particularly promising [ 5 , 6 ]. Several in vitro and pre-clinical animal studies have demonstrated that ASC exert beneficial effects on wounds [ 5 , 7 , 8 , 9 , 10 ].…”

“…In this respect, cell therapy based on adipose-derived stromal cells (ASC) has emerged as particularly promising [ 5 , 6 ]. Several in vitro and pre-clinical animal studies have demonstrated that ASC exert beneficial effects on wounds [ 5 , 7 , 8 , 9 , 10 ]. ASC promote healing [ 11 ]; suppress excessive inflammatory responses [ 12 , 13 , 14 ]; increase survival and proliferation of fibroblasts allowing ExtraCellular Matrix (ECM) remodeling [ 15 , 16 ]; produce anti-fibrotic factors [ 17 ]; and promote neovascularization [ 18 ].…”

“…Several human clinical trials have also been reported worldwide, most of them of limited reliability (i.e., uncontrolled studies). The appearance in recent years of a few well-conducted controlled studies has provided a new perspective to interpret the efficacy of ASC-based therapies for patients with chronic wounds [ 5 ]. Some recent and controlled trials reported that expanded ASC or the stromal vascular fraction have a superior efficacy compared with the control group, with a satisfactory safety profile.…”

Can the Autogenous Nanofat Injection Improve the Symptoms of Patients With Temporomandibular Joint Internal Derangement? A Prospective Observational Clinical Study

“…Pain reduction in those patients is related to the ADSCs exhibiting immunosuppressive characteristics and minimal immunogenicity, making them excellent for transplantation to painful and injured sites; also, their ability to release trophic factors improves the therapeutic and corrective outcome 33,34 …”