title: Transplantation of Immortalized CD34+ and CD34- Adipose-Derived Stem Cells Improve Cardiac Function and Mitigate Systemic Pro-Inflammatory Responses.
abstract: Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34- mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34- mADSCshTERT demonstrated phenotypic characteristics and multi-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34- mADSCshTERT, whereas CD34- mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34- mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34- mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCshTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34- mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34- mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.
authors: Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors: Jong-Ho
authors: JH
authors: Kim
authors: Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors: Seung-Cheol
authors: SC
authors: Choi
authors: Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors: Chi-Yeon
authors: CY
authors: Park
authors: Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors: Jae-Hyoung
authors: JH
authors: Park
authors: Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors: Ji-Hyun
authors: JH
authors: Choi
authors: Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors: Hyung-Joon
authors: HJ
authors: Joo
authors: Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors: Soon-Jun
authors: SJ
authors: Hong
authors: Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
authors: Do-Sun
authors: DS
authors: Lim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D016207:Cytokines / Q000097:blood; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D009203:Myocardial Infarction / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D019899:Paracrine Communication; D010641:Phenotype; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D018836:Inflammation Mediators; C509186:TERT protein, human; D019098:Telomerase