Autologous c-Kit plus Mesenchymal Stem Cell Injections Provide Superior Therapeutic Benefit as Compared to c-Kit plus Cardiac-Derived Stem Cells in a Feline Model of Isoproterenol-Induced Cardiomyopathy

作者：Taghavi Sharven; Sharp Thomas E III; Duran Jason M; Makarewich Catherine A; Berretta Remus M; Starosta Tim; Kubo Hajime; Barbe Mary; Houser Steven R^*

来源：Clinical and Translational Science, 2015, 8(5): 425-431.

DOI：10.1111/cts.12251

• heart failure
• cardiomyopathy
• cardiovascular diseases

BackgroundCardiac- (CSC) and mesenchymal-derived (MSC) CD117+ isolated stem cells improve cardiac function after injury. However, no study has compared the therapeutic benefit of these cells when used autologously.
MethodsMSCs and CSCs were isolated on day 0. Cardiomyopathy was induced (day 28) by infusion of L-isoproterenol (1,100 ug/kg/hour) from Alzet minipumps for 10 days. Bromodeoxyuridine (BrdU) was infused via minipumps (50 mg/mL) to identify proliferative cells during the injury phase. Following injury (day 38), autologous CSC (n = 7) and MSC (n = 4) were delivered by intracoronary injection. These animals were compared to those receiving sham injections by echocardiography, invasive hemodynamics, and immunohistochemistry.
ResultsFractional shortening improved with CSC (26.9 1.1% vs. 16.1 +/- 0.2%, p = 0.01) and MSC (25.1 +/- 0.2% vs. 12.1 +/- 0.5%, p = 0.01) as compared to shams. MSC were superior to CSC in improving left ventricle end-diastolic (LVED) volume (37.7 +/- 3.1% vs. 19.9 +/- 9.4%, p = 0.03) and ejection fraction (27.7 +/- 0.1% vs. 19.9 +/- 0.4%, p = 0.02). LVED pressure was less in MSC (6.3 +/- 1.3 mmHg) as compared to CSC (9.3 +/- 0.7 mmHg) and sham (13.3 +/- 0.7); p = 0.01. LV BrdU+ myocytes were higher in MSC (0.17 +/- 0.03%) than CSC (0.09 +/- 0.01%) and sham (0.06 +/- 01%); p < 0.001.
ConclusionsBoth CD117+ isolated CSC and MSC therapy improve cardiac function and attenuate pathological remodeling. However, MSC appear to confer additional benefit.

• 出版日期2015-10