Open AccessTransplantation of Immortalized CD34+ and CD34- Adipose-Derived Stem Cells Improve Cardiac Function and Mitigate Systemic Pro-Inflammatory Responses
Author(s) -
Jong Ho Kim,
Seung Cheol Choi,
Chi-Yeon Park,
Jae Hyoung Park,
Ji Hyun Choi,
Hyung Joon Joo,
Soon Jun Hong,
Do Sun Lim
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0147853
Subject(s) - cd34 , stem cell , transplantation , biology , immunology , cancer research , microbiology and biotechnology , andrology , medicine
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 (mADSCs hTERT ) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCs hTERT 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- mADSCs hTERT demonstrated phenotypic characteristics and multi-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCs hTERT exhibited a higher proliferation ability compared to CD34- mADSCs hTERT , whereas CD34- mADSCs hTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCs hTERT . Primary mADSCs, CD34+, and CD34- mADSCs hTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCs hTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCs hTERT . IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCs hTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCs hTERT 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- mADSCs hTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCs hTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCs hTERT groups compared to the AMI-induced control group. Transplantation of CD34- mADSCs hTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCs hTERT groups. GFP-tagged CD34+ and CD34- mADSCs hTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo .