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Mouse c‐kit + Cardiac Progenitor Cells Do not Age Gracefully
Author(s) -
Castaldi Alessandra,
Dodia Ramsinh Mansinh,
Orogo Amabel M.,
Najor Rita H.,
Gustafsson Asa B.,
Brown Joan Heller,
Purcell Nicole H.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1070.16
Subject(s) - mitochondrial biogenesis , progenitor cell , senescence , biology , downregulation and upregulation , population , lin28 , microbiology and biotechnology , mef2c , stem cell , mitochondrion , medicine , andrology , gene expression , cancer research , gene , induced pluripotent stem cell , genetics , embryonic stem cell , environmental health
Although c‐kit + cardiac progenitor cells (CPCs) are currently used in clinical trials there remain considerable gaps in our understanding of the molecular mechanisms underlying their proliferation and differentiation. Despite the fact that cardiac injury affects mainly the older human population, studies aimed at understanding CPC biology and their ability to contribute to cardiac regeneration have been performed on young animal models. In the present study we asked whether CPCs isolated from young (3 month) and aged (24 month) mice present different characteristics that could account for different outcomes in future CPC‐based therapeutic treatments for cardiac injury. We observed morphological differences and increased senescence as measure by the presence of senescence associated β‐galactosidase and increased p16 mRNA. The aged CPCs proliferated slower than their young counterpart and the expression of the stemness marker LIN28 was extremely low in the lines. We subsequently treated the cells with Dexamethasone (Dex), routinely used to induce cardiac commitment in CPCs, for 7 days and analyzed the expression of cardiac lineage marker genes. While MEF2C, GATA4, GATA6 and PECAM mRNAs were significantly upregulated in response to Dex treatment in young CPCs, their expression was not increased in aged CPCs. Interestingly, Dex treatment of aged CPCs failed to increase mitochondrial biogenesis and expression of the mitochondrial protein Complex III and IV, consistent with a defect in mitochondria complex assembly in the aged CPCs. This study should have an impact on the design of future CPC‐based therapeutic approaches for the treatment of older patients suffering from cardiac injury. Support or Funding Information This work was supported by grants from the National Heart, Lung and Blood Institute Grants: HL085577 (JHB, NHP, ÅBG and AC), HL028143 (JHB), HL114949 (NHP), and HL087023 (ÅBG) and by the National Institutes of Health NRSA Predoctoral Fellowship HL123309 (AMO). ÅBG is supported by an AHA Established Investigator Award.