Clinical Efficacy and Safety of Injection of Stromal Vascular Fraction Derived from Autologous Adipose Tissues in Systemic Sclerosis Patients with Hand Disability: A Proof-Of-Concept Trial.

Youngjae Park,Yoon Jae Lee,Jung Hee Koh,Jennifer Lee,Jong Won Rhie,Moon Young Kim,Wan-Uk Kim,Ki Joo Kim,Hong-Ki Min,Seung-Ki Kwok,Sung-Hwan Park,Su Jin Lee,Suk-Ho Moon

doi:10.3390/jcm9093023

Abstract

Background: Stromal vascular fraction (SVF) has recently emerged as a potential therapeutic modality, due to its multipotent cellular components in tissue regeneration. Systemic sclerosis (SSc) is a progressive autoimmune disease that results in hand disability by skin fibrosis and microangiopathies. We performed an open-label study to investigate the efficacy and safety of SVF injection in SSc patients (Clinical Trial number: NCT03060551). Methods: We gathered 20 SSc patients with hand disability, planning for a 24-week follow-up period. SVF was extracted from autologous adipose tissues, processed by the closed system kit, and injected into each finger of SSc patients. We observed various efficacy and safety profiles at each follow-up visit. Results: Among the 20 initially enrolled patients, eighteen received SVF injection, and were completely followed-up for the whole study period. Patients received 3.61 × 106 mesenchymal stem cells into each finger on average. Skin fibrosis, hand edema, and quality of life were significantly improved, and 31.6% of active ulcers were healed at 24 weeks after injections. Semiquantitative results of nailfold capillary microscopy were ameliorated. There was no single serious adverse event related to the procedure. Conclusions: Injection of SVF derived from autologous adipose tissues is tolerable, and shows clinical efficacy in SSc patients.

Highlights

Systemic sclerosis (SSc) is a progressive autoimmune disease that affects multiple internal and external organs by pathogenetic mechanisms that mainly include microangiopathies and fibrosis [1]
Recently updated treatment guidelines from the European League against Rheumatism (EULAR) covered approved treatment options based on literature reviews, only limited therapies received a high level of recommendation [2]
fluorescence-activated cell sorting (FACS) data showed that 75.1 and 99.2% of adherent cells were positive for CD73 and CD13, respectively, on average, whereas 3.9 and 3.3% of cells were positive for CD34 and HLA, respectively. These results suggest that most adherent cells have adipose-derived stem cells (ASC)-like cellular characteristics

Summary

Introduction

Systemic sclerosis (SSc) is a progressive autoimmune disease that affects multiple internal and external organs by pathogenetic mechanisms that mainly include microangiopathies and fibrosis [1]. Hand disability is one of the most frequently observed and QOL-influencing clinical features in patients with SSc, but remains a poorly solved issue in terms of therapeutic methods, as are other systemic involvements of SSc [3] Various phenotypes, such as Raynaud’s phenomenon, digital ulcers, skin fibrosis, and joint synovitis or contractures, are included in this category [4]. Intravenous injection of iloprost, one of the synthetic prostanoids, is proved to have efficacy in the healing of digital ulcers, while bosentan, an endothelin receptor antagonist, reduces the additional development of digital ulcers in SSc patients [2] All these treatments have various adverse effects and limitations to maintaining persistent application for long periods. Conclusions: Injection of SVF derived from autologous adipose tissues is tolerable, and shows clinical efficacy in SSc patients

Methods

Findings

Discussion

Conclusion