Abstract
Adipose-derived regenerative cell (ADRC) is a promising alternative source of autologous somatic stem cells for the repair of damaged tissue. This study aimed to assess the safety and feasibility of autologous ADRC implantation for therapeutic angiogenesis in patients with critical limb ischaemia (CLI). A clinical pilot study—Therapeutic Angiogenesis by Cell Transplantation using ADRCs (TACT-ADRC) study—was initiated in Japan. Adipose tissue was obtained by ordinary liposuction method. Isolated ADRCs were injected into the ischaemic limb. We performed TACT-ADRC procedure in five patients with CLI. At 6 months, no adverse events related to the TACT-ADRC were observed. No patients required major limb amputation, and ischaemic ulcers were partly or completely healed during the 6-month follow-up. In all cases, significant clinical improvements were seen in terms of rest pain and 6-min walking distance. Numbers of circulating CD34+ and CD133+ cells markers of progenitor cell persistently increased after ADRC implantation. The ratio of VEGF-A165b (an anti-angiogenic isoform of VEGF) to total VEGF-A in plasma significantly decreased after ADRC implantation. In vitro experiments, cultured with ADRC-conditioned media (CM) resulted in increased total VEGF-A and decreased VEGF-A165b in C2C12 cells, but not in macrophages. ADRC-CM also increased CD206+ cells expression and decreased TNF-α in macrophages. Autologous ADRC implantation was safe and effective in patients with CLI and could repair damaged tissue via its ability to promote angiogenesis and suppress tissue inflammation.
Highlights
Adipose-derived regenerative cell (ADRC) is a promising alternative source of autologous somatic stem cells for the repair of damaged tissue
Three patients had critical limb ischaemia (CLI) caused by collagen disease-associated vasculitis (CDV), one patient had CLI caused by thromboangiitis obliterans (TAO), and one patient had CLI caused by a combination of peripheral artery disease (PAD) and CDV
We reported that ADRC implantation augmented ischaemia-induced angiogenesis via an increase in EPC mobilization by the paracrine effect of VEGF and SDF-111; the number of circulating progenitor cells, such as CD34+ and CD133+ cells, persistently increased in responders up to 1 month after BM-MNC implantation[18]
Summary
Adipose-derived regenerative cell (ADRC) is a promising alternative source of autologous somatic stem cells for the repair of damaged tissue. This study aimed to assess the safety and feasibility of autologous ADRC implantation for therapeutic angiogenesis in patients with critical limb ischaemia (CLI). Autologous ADRC implantation was safe and effective in patients with CLI and could repair damaged tissue via its ability to promote angiogenesis and suppress tissue inflammation. IV III Unmeasured marrow-derived mononuclear cell (BM-MNC) implantation in patients with CLI in the first clinical pilot trial— Therapeutic Angiogenesis by Cell Transplantation (TACT)[5]. To assess the safety and feasibility of intramuscular autologous ADRC implantation in patients with CLI, we initiated a clinical pilot study—Therapeutic Angiogenesis by Cell Transplantation using ADRCs (TACT-ADRC) study—in Japan and analysed its results (UMIN ID: UMIN000010143; 01/03/2013)
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