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1.
Figure 5

Figure 5. Cell apoptosis. From: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

A) & B) Representative images of TUNEL-positive cells in the infarcted hearts of mice 3 weeks after cell treatment with CDCs (A) and PBS (B). C) Quantitative assessment of TUNEL-positive cells in the myocardium of mice treated with different cell types and control, is shown (n=3 mice per group). Bar = 500 um.

Tao-Sheng Li, et al. J Am Coll Cardiol. ;59(10):942-953.
2.
Figure 8

Figure 8. Comparison of purified c-kit+ stem cells and unsorted CDCs. From: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

A) 3 weeks after infarction, LVEF was higher in mice that received unsorted CDCs than those with c-kit+ cells purified from the same CDCs, although these purified c-kit+ stem cells also improved cardiac function when compared to controls injected with saline only. B) Although the same number of cells was used for culture, the purified c-kit+ stem cells released less VEGF, SDF, IGF-1, and HGF than the unsorted CDCs.

Tao-Sheng Li, et al. J Am Coll Cardiol. ;59(10):942-953.
3.
Figure 6

Figure 6. Cardiac function. From: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

LVEF at baseline (4 hrs post-MI) did not differ among groups, indicating a similar infarct size in animals of all groups. After 3 weeks, LVEF was higher in mice implanted with CDCs, compared to controls injected with saline only. Differences between any other two groups are not significant. Data are presented as mean ± SEM.

Tao-Sheng Li, et al. J Am Coll Cardiol. ;59(10):942-953.
4.
Figure 4

Figure 4. Cell engraftment and in vivo myogenic differentiation. From: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

A) Immunostaining shows some human CDCs (green, HNA) expressing α-sarcomeric actin, indicating myogenic differentiation, 3 weeks after implantation into infarcted mice hearts. B) Quantitation of engraftment (HNA+ cells). C) Quantitation of cardiomyocytes differentiated from transplanted human cells (HNA+/α-SA+ cells). Bar = 20 um. D) Quantitation of engraftment by quantitative PCR (n=3 mice per group).

Tao-Sheng Li, et al. J Am Coll Cardiol. ;59(10):942-953.
5.
Figure 2

Figure 2. Comparison of in vitro production of growth factors from cells cultured. From: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

Concentrations of angiopoietin-2, bFGF, HGF, IGF-1, SDF-1, and VEGF, measured by ELISA (n=3), are depicted (A). B) Schematic depicting the secretion of each of the six cytokines in each given cell type, as wheel-and-spoke diagrams in which the length of each spoke is proportional to the growth factor concentration in conditioned media and is normalized to that from CDCs. The symmetrical starburst pattern highlights the uniquely well-balanced paracrine profile of CDCs.

Tao-Sheng Li, et al. J Am Coll Cardiol. ;59(10):942-953.
6.
Figure 1

Figure 1. Morphology and phenotype characterization. From: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

A) Representative images of cardiosphere-derived stem cells (CDCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose tissue-derived mesenchymal stem cells (AD-MSCs), and bone marrow-derived mononuclear cells (BM-MNCs) after 3 days in culture under 20% O2. CDCs, BM-MSCs, and AD-MSCs demonstrate adherent growth and stromal (mesenchymal) cell-like morphology; BM-MNCs have smaller size and round shape. B) Expression profile of CD29, CD31, CD34, CD45, CD90, CD117 (c-kit), and CD133 in CDCs, BM-MSCs, AD-MSCs, and BM-MNCs. Bar = 50 μm.

Tao-Sheng Li, et al. J Am Coll Cardiol. ;59(10):942-953.
7.
Figure 7

Figure 7. Ventricular remodeling. From: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

A) Representative images of Masson’s staining of infarcted mice hearts, after implantation of different types of human cells or saline injection only. Quantitative analyses (n=3 mice per group) of LV wall thickness (B) and infarct perimeter (C) show that remodeling was attenuated more efficiently by CDC implantation, compared with BM-MSCs, AD-MSCs, and BM-MNC treatment, although implantation of BM-MSCs, AD-MSCs, and BM-MNCs resulted in less remodeling compared to control treatment with saline injection only.

Tao-Sheng Li, et al. J Am Coll Cardiol. ;59(10):942-953.
8.
Figure 3

Figure 3. In vitro myogenic differentiation and angiogenesis assay. From: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

A) Troponin T, with distinct myocyte-like appearance, was expressed spontaneously in a fraction of CDCs cultured for 7 days. This cardiac-specific marker was rarely expressed in BM-MSCs, AD-MSCs, and BM-MNCs. B) Quantitative analysis of Troponin T expression (n=3) in CDCs (9% of the cells positive), BM-MSCs (0.4% positive) and AD-MSCs and BM-MNCs (approximately 0.1% positive). C) CDCs, BM-MSCs, and AD-MSCs produced capillary-like tube formations in extracellular matrix. BM-MNCs did not form similar structures under these conditions. D) Quantitation and comparison of tube formation capacity by the different cell types (n=3). Bars = 50 um.

Tao-Sheng Li, et al. J Am Coll Cardiol. ;59(10):942-953.

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