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Age-Dependency in Cardiac Progenitor Cell Therapy

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Review of “Age-Dependent Effect of Pediatric Cardiac Progenitor Cells after Juvenile Heart Failure” from Stem Cells Translational Medicine by Stuart P. Atkinson

Age represents a key a parameter affecting the therapeutic value of stem/progenitor cells and how patients react to said therapeutics. However, the majority of studies, including those looking into cardiac progenitor cell therapy for heart failure, represent data relating to adults [1, 2].

In order to correct this knowledge gap, the laboratory of Michael E. Davis (Emory University, Atlanta, USA) has been studying the effect of human cardiac progenitor cells (CPC) taken from patients ranging from 0 to 5 years in a rat model of juvenile heart failure. In their new Stem Cells Translational Medicine study, the authors demonstrate that the therapeutic potential of hCPCs is age-dependent, with neonatal CPC treatment exhibiting the best results [3]. 

The researchers collected hCPCs from three age groups (neonate [0 days to 1 month], infant [1 month to 1 year], and child [1 to 5 years]) for injection into the ventricle musculature of an adolescent rat model of heart failure. While the age of the cells did not affect the retention of cells in the heart, which remained stable at around 20% at day 21 after injection, the authors observed a direct correlation between hCPC age and cardiac function and remodeling at 28 days. 

Specifically, the neonate hCPCs performed better than the infant or child hCPCs, likely due to increased chemotactic and proliferative capabilities and the increased recruitment of stem cell antigen 1-positive cells (See Figure), surmised to represent various progenitor cell types. Gene array data also highlighted a neonate-specific upregulation in the expression of genes associated with cell-cycle regulation, development, angiogenesis, anti-inflammatory response, regeneration, and anti-apoptosis.

This study suggests that the regenerative/reparative potential of human cardiac progenitor cell therapy is age dependent, with the youngest cells having the highest potential. Further examination of these cells may highlight which proteins and pathways mediate heightened therapeutic potential and reveal potentially druggable targets. Therefore, future studies may also lead to improved transplant outcomes when using older hCPCs or the creation of cell-free treatment strategies for heart failure.

References

  1. Bolli R, Chugh AR, D'Amario D, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 2011;378:1847-1857.
  2. Makkar RR, Smith RR, Cheng K, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 2012;379:895-904.
  3. Agarwal U, Smith AW, French KM, et al. Age-Dependent Effect of Pediatric Cardiac Progenitor Cells After Juvenile Heart Failure. Stem Cells Transl Med 2016;5:883-892.