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A Perfect Stem Cell Source to Treat the Damaged Heart?

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Review of “Cardiac Adipose-Derived Stem Cells Exhibit High Differentiation Potential to Cardiovascular Cells in C57BL/6 Mice” from Stem Cells Translational Medicine by Stuart P. Atkinson

Research aimed at stem cell treatment for the damaged heart relies heavily on stem/progenitor cells derived from peripheral blood and bone marrow. However, these sources come with certain disadvantages, and so other more amenable stem cell reservoirs have been sought after.

Researchers from the laboratory of Michio Asahi (Osaka Medical College, Japan) sought to assess the potential of adipose tissue-derived stem cells (AdSCs) from various anatomical sites, given that these cells can differentiate into cardiovascular lineage cells [1-3] and are easily isolated in large numbers. To do this, the group isolated and assessed mouse AdSCs from subcutaneous, visceral, subscapular, and cardiac fat tissues and compared their stem cell function and cardiac differentiation potential [4]. Could their results point to an effective and reliable source of cells for the treatment of the damaged heart?

Of the adipose tissues tested, cardiac brown adipose tissue (CA) exhibited the highest AdSC count and density, demonstrated the highest proliferative rate, and exhibited an enhanced endothelial and cardiac differentiation potential. To test their regenerative/reparative potential in mouse, the authors then systemically transfused AdSCs derived from various sources and assessed their recruitment to ischemic myocardium as a model for the treatment of myocardial infarction (MI). Excitingly, the CA-derived cells had the unique ability to migrate and differentiate into vascular lineage cells and cardiomyocytes by 7 days post transfusion. Additionally, following injection into the heart, CA-derived AdSCs mediated a significantly higher recovery in cardiac function, a reduction in the infarct area (See figure for PBS-control vs CA-derived AdSCs and AdSCs from subcutaneous white adipose tissue), and an increase in the capillary density in the ischemic border zone.

Its seems plain that the source of origin of AdSCs will have a significant impact on their therapeutic worth and, hopefully, a similar assessment in humans will lead us towards the construction of an optimized autologous cell therapy for MI. But if the results stand, the question still remains whether this source – cardiac adipose – is relevant. Can we collect and purify sufficient numbers of cells to be clinically relevant, or will we have to amplify these cells in vitro? Furthermore, will long-term expansion affect their capabilities? Encouragingly, the authors do note that they used relatively small amounts of cells (10,000) and the source (below the thymus in a region free of major vessels in human [5]) is likely to be relatively free from risk, and easily accessible in patients already undergoing cardiovascular procedures.

Discussion Points

  • Is cardiac adipose tissue a relevant source of stem cells?
  • Will we need to amplify these cells to clinically relevant numbers and will they still have the same potent effect at the end of long-term culture?
  • What makes stem cells from different sources behave in a tissue-specific manner?

References

  1. Planat-Benard V, Menard C, Andre M, et al. Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 2004;94:223-229.
  2. Zhu F, Guo GH, Chen W, et al. Effects of bone marrow-derived mesenchymal stem cells engraftment on vascular endothelial cell growth factor in lung tissue and plasma at early stage of smoke inhalation injury. World J Emerg Med 2010;1:224-228.
  3. Harris LJ, Abdollahi H, Zhang P, et al. Differentiation of adult stem cells into smooth muscle for vascular tissue engineering. J Surg Res 2011;168:306-314.
  4. Nagata H, Ii M, Kohbayashi E, et al. Cardiac Adipose-Derived Stem Cells Exhibit High Differentiation Potential to Cardiovascular Cells in C57BL/6 Mice. Stem Cells Transl Med 2016;5:141-151.
  5. Cheung L, Gertow J, Werngren O, et al. Human mediastinal adipose tissue displays certain characteristics of brown fat. Nutr Diabetes 2013;3:e66.