Human Thymus Mesenchymal Stromal Cells Augment Force Production in Self-Organized Cardiac Tissue

Stem Cell Program, University of California Davis, Sacramento, California, USA.
The Annals of thoracic surgery (Impact Factor: 3.85). 09/2010; 90(3):796-803; discussion 803-4. DOI: 10.1016/j.athoracsur.2010.04.080
Source: PubMed


Mesenchymal stromal cells have been recently isolated from thymus gland tissue discarded after surgical procedures. The role of this novel cell type in heart regeneration has yet to be defined. The purpose of this study was to evaluate the therapeutic potential of human thymus-derived mesenchymal stromal cells using self-organized cardiac tissue as an in vitro platform for quantitative assessment.
Mesenchymal stromal cells were isolated from discarded thymus tissue from neonates undergoing heart surgery and were incubated in differentiation media to demonstrate multipotency. Neonatal rat cardiomyocytes self-organized into cardiac tissue fibers in a custom culture dish either alone or in combination with varying numbers of mesenchymal stromal cells. A transducer measured force generated by spontaneously contracting self-organized cardiac tissue fibers. Work and power outputs were calculated from force tracings. Immunofluorescence was performed to determine the fate of the thymus-derived mesenchymal stromal cells.
Mesenchymal stromal cells were successfully isolated from discarded thymus tissue. After incubation in differentiation media, mesenchymal stromal cells attained the expected phenotypes. Although mesenchymal stromal cells did not differentiate into mature cardiomyocytes, addition of these cells increased the rate of fiber formation, force production, and work and power outputs. Self-organized cardiac tissue containing mesenchymal stromal cells acquired a defined microscopic architecture.
Discarded thymus tissue contains mesenchymal stromal cells, which can augment force production and work and power outputs of self-organized cardiac tissue fibers by several-fold. These findings indicate the potential utility of mesenchymal stromal cells in treating heart failure.

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    • "However, further studies assessed that, following specific molecular cues, MSCs reached the site of injury and allowed the repair of tissues by means of the expression of different trophic factors [8–10]. In the last 20 years, MSCs were isolated from a wide range of tissues [11–14] and organs [15, 16]. Furthermore, it was demonstrated that under specific stimuli MSCs possessed an incredible capacity of transdifferentiation, developing in mesodermal (myocyte, osteocyte, endothelium, adipocyte, and cardiomyocyte), ectodermal (neuronal), and endodermal (hepatic, pancreatic, respiratory epithelium) lineages. "
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    • "Cells were isolated from neonatal Sprague–Dawley rats (Charles River Laboratories, Wilmington, MA, USA) 2– 4 days of age as described (Sondergaard et al. 2010). The isolated cells were suspended in a plating medium (PM) consisting in 64 % (v/v) M199, 20 % F12K, 7 % fetal bovine serum, 7 % calf bovine serum, 1 % penicillinstreptomycin (all Invitrogen), 40 ng/ml hydrocortisone, 25 μg/ml 6-aminocaproic acid and 30 μg/ml ascorbic acid (all Sigma-Aldrich). "
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    • "The EHT model that was used in this study is based on the self-organization of neonatal rat cardiac cells as described previously [3], [10]. All procedures involving laboratory animals were done in accordance with protocols approved by the University of California Davis Institutional Animal Care and Use Committee. "
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