Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study.
BACKGROUND
Recent studies have demonstrated that mesenchymal stem cells (MSCs) modulate the immune response and reduce lung injury in animal models. Currently, no clinical studies of the effects of MSCs in acute respiratory distress syndrome (ARDS) exist. The objectives of this study were first to examine the possible adverse events after systemic administration of allogeneic adipose-derived MSCs in ARDS patients and second to determine potential efficacy of MSCs on ARDS.


METHODS
Twelve adult patients meeting the Berlin definition of acute respiratory distress syndrome with a PaO2/FiO2 ratio of < 200 were randomized to receive allogeneic adipose-derived MSCs or placebo in a 1:1 fashion. Patients received one intravenous dose of 1 × 106 cells/kg of body weight or saline. Possible side effects were monitored after treatment. Acute lung injury biomarkers, including IL-6, IL-8 and surfactant protein D (SP-D), were examined to determine the effects of MSCs on lung injury and inflammation.


RESULTS
There were no infusion toxicities or serious adverse events related to MSCs administration and there were no significant differences in the overall number of adverse events between the two groups. Length of hospital stay, ventilator-free days and ICU-free days at day 28 after treatment were similar. There were no changes in biomarkers examined in the placebo group. In the MSCs group, serum SP-D levels at day 5 were significantly lower than those at day 0 (p = 0.027) while the changes in IL-8 levels were not significant. The IL-6 levels at day 5 showed a trend towards lower levels as compared with day 0, but this trend was not statistically significant (p = 0.06).


CONCLUSIONS
Administration of allogeneic adipose-derived MSCs appears to be safe and feasible in the treatment of ARDS. However, the clinical effect with the doses of MSCs used is weak, and further optimization of this strategy will probably be required to reach the goal of reduced alveolar epithelial injury in ARDS.


BACKGROUND
Clinical trials.gov, NCT01902082.
Guoping
G
Zheng
Lanfang
L
Huang
Haijiang
H
Tong
Qiang
Q
Shu
Yaoqin
Y
Hu
Menghua
M
Ge
Keqin
K
Deng
Liuya
L
Zhang
Bin
B
Zou
Baoli
B
Cheng
Shaoxing Second Hospital, 123 Yan An Road, Shaoxing, Zhejiang 312000, China. jxu5@yahoo.com.
Jianguo
J
Xu
D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002478:Cells, Cultured; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010865:Pilot Projects; D012128:Respiratory Distress Syndrome / Q000175:diagnosis* / Q000601:surgery*; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult