Haeyeon Seo1,2, Ho Joong Choi1, Ok-Hee Kim1,2, Jung Hyun Park2,3, Ha Eun Hong1,2, Say-June Kim4,5,6. 1. Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea. 2. Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. 3. Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea. 4. Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea. sayjunekim@gmail.com. 5. Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. sayjunekim@gmail.com. 6. Catholic Central Laboratory of Surgery, Department of Surgery, Division of Hepatobiliary pancreatic surgery. Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo- daero, Seocho-gu, 06591, Seoul, Republic of Korea. sayjunekim@gmail.com.
Abstract
BACKGROUND: Hypoxic preconditioning (HP) is a stem cell preconditioning modality designed to augment the therapeutic effects of mesenchymal stem cells (MSCs). Although autophagy is expected to play a role in HP, very little is known regarding the relationship between HP and autophagy. METHODS AND RESULTS: The adipose-derived stem cell (ASC)-secretome obtained under normoxia (NCM) and ASC-secretome obtained under HP (HCM) were obtained by culturing ASCs for 24 h under normoxic (21% partial pressure of O2) and hypoxic (1% partial pressure of O2) conditions, respectively. Subsequently, to determine the in vivo effects of HCM, each secretome was injected into 70% partially hepatectomized mice, and liver specimens were obtained. HCM significantly reduced the apoptosis of thioacetamide-treated AML12 hepatocytes and promoted the autophagic processes of the cells (P < 0.05). Autophagy blockage by either bafilomycin A1 or ATG5 siRNA significantly abrogated the anti-apoptotic effect of HCM (P < 0.05), demonstrating that HCM exerts its anti-apoptotic effect by promoting autophagy. The effect of HCM - reduction of cell apoptosis and promotion of autophagic process - was also demonstrated in a mouse model. CONCLUSIONS: HP appears to induce ASCs to release a secretome with enhanced anti-apoptotic effects by promoting the autophagic process of ASCs.
BACKGROUND: Hypoxic preconditioning (HP) is a stem cell preconditioning modality designed to augment the therapeutic effects of mesenchymal stem cells (MSCs). Although autophagy is expected to play a role in HP, very little is known regarding the relationship between HP and autophagy. METHODS AND RESULTS: The adipose-derived stem cell (ASC)-secretome obtained under normoxia (NCM) and ASC-secretome obtained under HP (HCM) were obtained by culturing ASCs for 24 h under normoxic (21% partial pressure of O2) and hypoxic (1% partial pressure of O2) conditions, respectively. Subsequently, to determine the in vivo effects of HCM, each secretome was injected into 70% partially hepatectomized mice, and liver specimens were obtained. HCM significantly reduced the apoptosis of thioacetamide-treated AML12 hepatocytes and promoted the autophagic processes of the cells (P < 0.05). Autophagy blockage by either bafilomycin A1 or ATG5 siRNA significantly abrogated the anti-apoptotic effect of HCM (P < 0.05), demonstrating that HCM exerts its anti-apoptotic effect by promoting autophagy. The effect of HCM - reduction of cell apoptosis and promotion of autophagic process - was also demonstrated in a mouse model. CONCLUSIONS: HP appears to induce ASCs to release a secretome with enhanced anti-apoptotic effects by promoting the autophagic process of ASCs.
Authors: Nuh N Rahbari; O James Garden; Robert Padbury; Mark Brooke-Smith; Michael Crawford; Rene Adam; Moritz Koch; Masatoshi Makuuchi; Ronald P Dematteo; Christopher Christophi; Simon Banting; Val Usatoff; Masato Nagino; Guy Maddern; Thomas J Hugh; Jean-Nicolas Vauthey; Paul Greig; Myrddin Rees; Yukihiro Yokoyama; Sheung Tat Fan; Yuji Nimura; Joan Figueras; Lorenzo Capussotti; Markus W Büchler; Jürgen Weitz Journal: Surgery Date: 2011-01-14 Impact factor: 3.982
Authors: Jakub Tolar; Alma J Nauta; Mark J Osborn; Angela Panoskaltsis Mortari; Ron T McElmurry; Scott Bell; Lily Xia; Ning Zhou; Megan Riddle; Tania M Schroeder; Jennifer J Westendorf; R Scott McIvor; Pancras C W Hogendoorn; Karoly Szuhai; Leann Oseth; Betsy Hirsch; Stephen R Yant; Mark A Kay; Alexandra Peister; Darwin J Prockop; Willem E Fibbe; Bruce R Blazar Journal: Stem Cells Date: 2006-10-12 Impact factor: 6.277