Long-term repopulation of aged bone marrow stem cells using young Sca-1 cells promotes aged heart rejuvenation

Aging Cell
Jiao LiRen-Ke Li

Abstract

Reduced quantity and quality of stem cells in aged individuals hinders cardiac repair and regeneration after injury. We used young bone marrow (BM) stem cell antigen 1 (Sca-1) cells to reconstitute aged BM and rejuvenate the aged heart, and examined the underlying molecular mechanisms. BM Sca-1+ or Sca-1- cells from young (2-3 months) or aged (18-19 months) GFP transgenic mice were transplanted into lethally irradiated aged mice to generate 4 groups of chimeras: young Sca-1+ , young Sca-1- , old Sca-1+ , and old Sca-1- . Four months later, expression of rejuvenation-related genes (Bmi1, Cbx8, PNUTS, Sirt1, Sirt2, Sirt6) and proteins (CDK2, CDK4) was increased along with telomerase activity and telomerase-related protein (DNA-PKcs, TRF-2) expression, whereas expression of senescence-related genes (p16INK4a , P19ARF , p27Kip1 ) and proteins (p16INK4a , p27Kip1 ) was decreased in Sca-1+ chimeric hearts, especially in the young group. Host cardiac endothelial cells (GFP- CD31+ ) but not cardiomyocytes were the primary cell type rejuvenated by young Sca-1+ cells as shown by improved proliferation, migration, and tubular formation abilities. C-X-C chemokine CXCL12 was the factor most highly expressed in homed donor BM (GFP+ ) cells i...Continue Reading

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Citations

Feb 7, 2020·Aging·Faisal J Alibhai, Ren-Ke Li
Oct 10, 2020·World Journal of Stem Cells·Qing-Shu MengXiao-Ting Liang
Nov 21, 2020·Aging·Faisal J Alibhai, Ren-Ke Li
Jun 8, 2021·Frontiers in Cardiovascular Medicine·Jielei GuShiming Liu
May 9, 2021·Cardiovascular Research·Maggie S ChenJessica C Garbern
Jul 22, 2021·Seminars in Cell & Developmental Biology·Yi WangDa-Zhi Wang
Sep 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Arushi TanejaNagalingam Ravi Sundaresan

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Methods Mentioned

BETA
SMA
FACS
density gradient centrifugation

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