Chao Wang1, Xiaoming Li2, Hongxing Dang1, Ping Liu2, B O Zhang2, Feng Xu3. 1. Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014 China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014 China; Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, Chongqing, China. 2. State Key Lab of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China. 3. Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014 China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014 China; Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, Chongqing, China. Electronic address: xufeng9899@163.com.
Abstract
BACKGROUND: Insulin-like growth factor 2 (IGF2), an essential component of the stem cell niche, has been reported to modulate the proliferation and differentiation of stem cells. Previously, a continuous expression of IGF2 in tissues was reported to maintain the self-renewal ability of several types of stem cells. Therefore, in this study, we investigated the expression of IGF2 in adipose tissues and explored the effects of IGF2 on adipose-derived stromal cells (ADSCs) in vitro. METHODS: The expression pattern of IGF2 in rat adipose tissues was determined by gene expression and protein analyses. The effect of IGF2 on proliferation, stemness-related marker expression and adipogenic and osteogenic differentiation was systematically investigated. Furthermore, antagonists of IGF2-specific receptors-namely, BMS-754807 and picropodophyllin-were added to explore the underlying signal transduction mechanisms. RESULTS: IGF2 levels displayed a tendency to decrease with age in rat adipose tissues. After the addition of IGF2, isolated ADSCs displayed higher proliferation and expression of the stemness-related markers NANOG, OCT4 and SOX2 and greater differentiation potential to adipocytes and osteoblasts. Additionally, both type 1 insulin-like growth factor receptor (IGF-1R) and insulin receptor (IR) participated in the IGF2-mediated promotion of stemness in ADSCs. CONCLUSIONS: Our findings indicate that IGF2 could enhance the stemness of rat ADSCs via IGF-1R and IR and may highlight an effective method for the expansion of ADSCs for clinical application.
BACKGROUND:Insulin-like growth factor 2 (IGF2), an essential component of the stem cell niche, has been reported to modulate the proliferation and differentiation of stem cells. Previously, a continuous expression of IGF2 in tissues was reported to maintain the self-renewal ability of several types of stem cells. Therefore, in this study, we investigated the expression of IGF2 in adipose tissues and explored the effects of IGF2 on adipose-derived stromal cells (ADSCs) in vitro. METHODS: The expression pattern of IGF2 in rat adipose tissues was determined by gene expression and protein analyses. The effect of IGF2 on proliferation, stemness-related marker expression and adipogenic and osteogenic differentiation was systematically investigated. Furthermore, antagonists of IGF2-specific receptors-namely, BMS-754807 and picropodophyllin-were added to explore the underlying signal transduction mechanisms. RESULTS:IGF2 levels displayed a tendency to decrease with age in rat adipose tissues. After the addition of IGF2, isolated ADSCs displayed higher proliferation and expression of the stemness-related markers NANOG, OCT4 and SOX2 and greater differentiation potential to adipocytes and osteoblasts. Additionally, both type 1 insulin-like growth factor receptor (IGF-1R) and insulin receptor (IR) participated in the IGF2-mediated promotion of stemness in ADSCs. CONCLUSIONS: Our findings indicate that IGF2 could enhance the stemness of rat ADSCs via IGF-1R and IR and may highlight an effective method for the expansion of ADSCs for clinical application.
Authors: Abhishek Chandra; Anthony B Lagnado; Joshua N Farr; Megan Schleusner; David G Monroe; Dominik Saul; João F Passos; Sundeep Khosla; Robert J Pignolo Journal: J Bone Miner Res Date: 2022-03-29 Impact factor: 6.390