Abstract
Background
Many patients with collagen disease (CD), particularly systemic sclerosis (SSc) and collagen disease-associated vasculitis (CDV), develop critical limb ischemia (CLI) which leads to limb amputation. In SSc vasculopathy, intimal hyperplasia, abnormal vascular contraction, and intravascular micro thrombus due to autoimmune abnormalities are main causes of inadequate blood supply that lead to the development of CLI. Moreover, in CDV, presence of inflammation cells infiltrates and destruction of the vascular wall also lead to vascular stenosis or obstruction. However, conventional therapies including revascularization via surgical bypass showed poor outcomes in CLI patients with CD. Therefore, establishment of new methods to improve peripheral circulation for limb salvage are required.
Purpose
After discovering that circulating endothelial progenitor cells (EPCs) mobilized from the bone marrow participate in postnatal neovascularization, autologous bone marrow-derived mononuclear cells (BM-MNCs) has been performed as a new treatment for many no-option CLI patients caused by arteriosclerosis obliterans, thromboangiitis obliterans or CD. In this study, we would like to assess the long-term clinical outcomes after autologous BM-MNCs implantation in CLI patients with SSc and CDV.
Methods
This study was a retrospective, multicenter, observational, and non-controlled study. We assessed no-option CLI patients with CD who were performed the autologous BM-MNCs implantation in 10 institutes. Overall survival (OS), major-amputation-free (MAF) and amputation-free survival (AFS) rates were primary endpoints of this study. In addition, we assessed improvements of ischemic pain as visual analogue scale (VAS) scores. Safety endpoints were defined as cardiovascular events and all-cause adverse events within 6 months after implantation.
Results
A total of 69 patients (39 with SSc–related diseases (SSc group) and 30 with CDV (CDV group)), were included in this study. The median follow-up duration was 36.5 months. The 10-year OS rate was 59.1% in the SSc group and 82.4% in the CDV group, respectively. The 10-year MAF rates were 97.4% and 82.6%, respectively. The 10-year AFS rates were 57.6% and 67.8%, respectively (Figure 1). The number of major or minor amputations in the SSc group trended to be less than that in the CDV group. In addition, significant improvement in VAS scores were observed in both groups (Figure 2). No patients died, no cardiovascular events, and no severe adverse events associated with BM-MNCs implantation were noted within 6 months after this therapy in both groups.
Figure 1
Conclusions
The BM-MNCs implantation may be feasible in no-option CLI patients with CD. Improvement of ischemic symptoms by BM-MNCs implantation was significant in both groups and, in the SSc group, limb salvage rate tended to be higher than the CDV group.
Characterization of Mesenchymal Stem Cells of “No-Options” Patients with Critical Limb Ischemia Treated by Autologous Bone Marrow Mononuclear Cells
