A clinical trial of autologous adipose-derived regenerative cell transplantation for a postoperative enterocutaneous fistula.
OBJECTIVE
Adipose-derived stem cell (ADSC) transplantation is expected to be a minimally invasive, but effective, treatment for postoperative enterocutaneous fistulas associated with poor blood flow and chronic inflammation. The aim of this study was to assess the safety and efficacy of a novel ADSC therapy for this condition.


METHODS
We conducted an open-label, single-arm exploratory phase I study to assess the safety and efficacy of a novel ADSC therapy. Using the Celution system, we isolated adipose-derived regenerative cells (ADRCs) containing abundant ADSCs from liposuction-obtained gluteal adipose tissue. A mixture of ADRCs and fibrin glue was subsequently transplanted into the fistula, and ADRCs were percutaneously and endoscopically injected around the fistula. We evaluated the safety and feasibility of ADRC transplantation and fistula closure in six patients (UMIN000007316).


RESULTS
ADRC transplantation was completed in all patients. The fistula closure rates were 83.3 % at 4 and 12 weeks and 100 % at 24 weeks. All patients had grade 1 pain and subcutaneous hemorrhage at the liposuction sites, but no serious adverse events related to this procedure were observed.


CONCLUSIONS
Transplantation of autologous ADRCs is safe, feasible and advantageous, as it can secure a sufficient cell count without culture or multiple passages, and will likely be effective for a postoperative enterocutaneous fistula.
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. tmizushima@gesurg.med.osaka-u.ac.jp.
Tsunekazu
http://orcid.org/0000-0002-0825-6823
T
Mizushima
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Hidekazu
H
Takahashi
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Hiroshi
H
Takeyama
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Atsushi
A
Naito
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Naotsugu
N
Haraguchi
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Mamoru
M
Uemura
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Junichi
J
Nishimura
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Taishi
T
Hata
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Ichiro
I
Takemasa
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Hirofumi
H
Yamamoto
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Yuichiro
Y
Doki
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Masaki
M
Mori
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000368:Aged; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage; D006801:Humans; D007412:Intestinal Fistula / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D015718:Fibrin Tissue Adhesive
Adipose-derived regenerative cells; Adipose-derived stem cells; Cell therapy; Enterocutaneous fistula