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Studying the Effect of Diabetes on Cardiac Therapy Relevant Stem Cells

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Review of “Chronic High-Fat Feeding Affects the Mesenchymal Cell Population Expanded From Adipose Tissue but Not Cardiac Atria” from Stem Cells Translational Medicine by Stuart P. Atkinson

Human adult stem cell transplants have the potential to be an effective treatment for heart failure through the paracrine support of the damaged heart and potentially differentiation and integration into the myocardium to replace lost cells. However, heart disease rarely appears without other “companion” ailments, such as type 2 diabetes mellitus (T2DM) which have the potential to impair the function of stem/progenitor populations [1, 2]. This includes cardiosphere-derived cells (CDCs) and adipose-derived mesenchymal cells (AD-MSCs) which have shown early stage short-term safety and therapeutic efficacy in treating heart failure [3, 4].

To assess the effect of a diabetic diet a study from Filippo Perbellini (Imperial College, London, UK) has compared the function of these therapeutically relevant stem cell types in mice fed on a high-fat diet (HFD) to mice fed on a standard diet. Their in-depth studies suggest that while HFD does not affect CDC function, it does alter the cellular content of the AD-MSC population with possible consequences to their regenerative abilities [5].

Mice fed on the HFD displayed the characteristic early diabetic phenotype, and in line with an increase in body fat, the authors also noted an increase in the yield of AD-MSCs at early culture passages, although they observed no increases in the quantity of CDCs isolated from atrial tissues. Encouragingly, stem cell culture times were not altered by diet, so suggesting that diabetic conditions will not affect the in vitro amplification of stem cells to therapeutically relevant levels.

Functional assessment found no significant effect of diet on CDCs or AD-MSCs in terms of VEGF secretion (Vascular endothelial growth factor – enhances vasculogenesis and arteriogenesis), cell migration, or stem cell clonogenic capability. However, while the characteristic surface marker expression and cardiac differentiation potential was not altered in CDCs from either diet group, HFD mice did present with an increase in markers indicative of a higher level of endothelial, fibroblast, and hematopoietic cell content in the collected AD-MSC population. Furthermore, AD-MSCs from the HFD mice displayed a slower response to cardiomyocyte differentiation conditions and a much lower expression of some key cardiac genes as compared to CDCs.

These comparisons demonstrate that CDCs remain unaffected by the early diabetic phenotype and have an enhanced ability to differentiate towards the cardiomyocyte lineage as compared to AD-MSCs. This supports the conclusion that CDCs may be the more clinically relevant cell type for the treatment of heart disease in patients suffering from other associated ailments.

References

  1. Tepper OM, Carr J, Allen RJ, Jr., et al. Decreased circulating progenitor cell number and failed mechanisms of stromal cell-derived factor-1alpha mediated bone marrow mobilization impair diabetic tissue repair. Diabetes 2010;59:1974-1983.
  2. Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002;106:2781-2786.
  3. Gutierrez E, Sanz-Ruiz R, Alvarez EV, et al. General overview of the Seventh International Symposium on Stem Cell Therapy and Cardiovascular Innovations. J Cardiovasc Transl Res 2011;4:115-120.
  4. 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.
  5. Perbellini F, Gomes RS, Vieira S, et al. Chronic High-Fat Feeding Affects the Mesenchymal Cell Population Expanded From Adipose Tissue but Not Cardiac Atria. Stem Cells Transl Med 2015;4:1403-1414.