title: Combination of CD34-positive cell subsets with infarcted myocardium-like matrix stiffness: a potential solution to cell-based cardiac repair.
abstract: Detection of the optimal cell transplantation strategy for myocardial infarction (MI) has attracted a great deal of attention. Commitment of engrafted cells to angiogenesis within damaged myocardium is regarded as one of the major targets in cell-based cardiac repair. Bone marrow-derived CD34-positive cells, a well-characterized population of stem cells, might represent highly functional endothelial progenitor cells and result in the formation of new blood vessels. Recently, physical microenvironment (extracellular matrix stiffness) around the engrafted cells was found to exert an essential impact on their fate. Stem cells are able to feel and respond to the tissue-like matrix stiffness to commit to a relevant lineage. Notably, the infarct area after MI experiences a time-dependent stiffness change from flexible to rigid. Our previous observations demonstrated myocardial stiffness-dependent differentiation of the unselected bone marrow-derived mononuclear cells (BMMNCs) along endothelial lineage cells. Myocardial stiffness (~42 kPa) within the optimal time domain of cell engraftment (at week 1 to 2) after MI provided a more favourable physical microenvironment for cell specification and cell-based cardiac repair. However, the difference in tissue stiffness-dependent cell differentiation between the specific cell subsets expressing and no expressing CD34 phenotype remains uncertain. We presumed that CD34-positive cell subsets facilitated angiogenesis and subsequently resulted in cardiac repair under induction of infarcted myocardium-like matrix stiffness compared with CD34-negative cells. If the hypothesis were true, it would contribute greatly to detect the optimal cell subsets for cell therapy and to establish an optimized therapy strategy for cell-based cardiac repair.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shuning
authors.initials: S
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Kang
authors.initials: K
authors.lastname: Yao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Zheyong
authors.initials: Z
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Juying
authors.initials: J
authors.lastname: Qian
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic; D014945:Wound Healing / Q000502:physiology*
chemical_list: D018952:Antigens, CD34
keywords: CD34-positive cells; endothelial cell lineage; matrix stiffness; myocardial infarction