Mesenchymal stromal cell therapy in ischemic heart disease

Figures & data

Figure 1. Mesenchymal stromal cells – mechanisms of action. (Reprint from Singer NG and Caplan AL. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011; 6:457–78. With permission from Annual Reviews).

Table 1. Mesenchymal stromal cells in patients with acute myocardial infarction.

Reference	No. of patients	Design	Donor	Dose	Delivery route	End-points
Chen et al. (2006) [31]	69	RPCT	Autologous	48–60 × 10^9	IC	Improved LVEF, LV dimensions, perfusion and wall motion
Katritsis et al. (2007) [33]	22	Open	Autologous	1–2 × 10^6	IC	Improved wall motion and perfusion
Hare et al. (2009) [19]	53	RPCT	Allogeneic	0.5/1.6/5 × 10^6/kg	IV	Improved FEV1. Not arrhythmogenic
Yang et al. (2010) [27]	16	Open	Autologous	10 × 10^6	IC	Safe and feasible
Houtgraaf et al. (2012) [28]	14	RPCT	Autologous	20 × 10^6	IC	Improved perfusion and scar tissue

FEV1: forced expiratory volume in 1 second; IC: intracoronary; IV: intravenous; LV: left ventricular; LVEF: left ventricular ejection fraction; RPCT: randomized placebo controlled trial.

Figure 2. Hospital admission rates per patient from 3 years before treatment to 3 years after treatment. NS: non-significant; PCI: percutane coronary intervention; UAP: unstable angina pectoris; AMI: acute myocardial infarction. (Reprinted from Mathiasen et al. Int J Cardiol. 2013 Dec 10;170(2):246–51) with permission from Elsevier).

Table 2. Mesenchymal stem cells in patients with chronic ischemic heart disease.

Reference	No. of patients	Donor	Design	Dose	Delivery route	End-points
Chen et al. (2006) [31]	22	Autologous	Open	5 × 10^6	IC	Improved LVEF and exercise capacity. Reduced symptoms
Mohyeddin-Bonab et al. (2007) [32]	8	Autologous	Open	5.55 × 10^6	IC/IM	Improved LVEF, reduced symptoms and infarct size
Katritsis et al. (2007) [33]	5	Autologous	Open	1.3–2.8 × 10^6	IC	Not arrhythmogenic
Williams et al. (2011) [34]	4	Autologous	Open	100/200 × 10^6	IM	Reduced LV dimensions and infarct size
Friis et al. (2011) [8]	31	Autologous	Open	21.5 × 10^6	IM	Improved LVEF and exercise capacity. Reduced symptoms.
Lasala et al. (2011) [35]	10	Autologous	Open	7.5 × 10^6	IC	Increased LVEF
Hare et al. (2012) [20]	30	Allogeneic/autologous	RO	20/100/200 × 10^6	IM	Safe and feasible
Mathiasen et al. (2015) [12]	60	Autologous	PPCT	Average 83 × 10^6	IM	Safe, improved LVEF, muscle mass
Perin et al. (2015) [21]	60	Allogeneic	RSCT	25/75/150 × 10^6	IM	Safe and feasible

IC: intracoronary; IM: intramyocardial; LV: left ventricular; LVEF: left ventricular ejection fraction; RO: randomized open study; RPCT: randomized placebo controlled trial; RSCT: randomized sham controlled trial.

Figure 3. Differences in cardiac function from baseline to 6-month follow-up. (A) End-systolic volume, (B) end-diastolic volume, (C) ejection fraction, (D) stroke volume, (E) cardiac output, (F) myocardial mass, and (G) scar tissue (Paired t-test. Bar values are mean ±95% confidence intervals). (Reprinted from Mathiasen et al. Eur Heart J. 2015 Jul 14;36(27):1744–53 with permission from Oxford University Press).

Figure 4. Dose–response effects: (A) end-systolic volume, (B) ejection fraction, and (C) mean myocardial mass. p Values represent the differences between subgroups of the mesenchymal stromal cell group (one-way ANOVA. Bar values are mean ±95% confidence intervals). (Reprinted from Mathiasen et al. Eur Heart J. 2015 Jul 14;36(27):1744–53 with permission from Oxford University Press).

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