[Bone marrow stem cells-based SERCA2a gene therapy for heart failure after acute myocardium infarction].
ABSTRACT Explore the possibility of MSC to be used to target delivery of therapeutic gene and evaluate the therapeutic effects among gene therapy, MSC transplantation and MSC-based gene therapy.
MSC were infected with an adenoviral expression vector carrying SERCA2a. SD female rats were used to make animal model with heart failure after AMI and divided into 4 groups randomly. Group I (n = 7) received SERCA2a gene therapy, group II (n = 7) received MSC transplantation, group III (n = 8) received MSC infected with SERCA2a gene transplantation, and group IV (n = 7) received empty adenoviral vector. Cardiac function was evaluated by echocardiography and physiological recorder. SERCA2a gene and protein expression were evaluated by RT-PCR and Western blot respectively.
Compared to group IV, EF and FS of group I, group II and group III were elevated significantly on 14 days after therapy (EF: 67.7 +/- 3.9, 62.6 +/- 4.0, 67.9 +/- 3.7 versus 45.0 +/- 2.2; FS: 33.9 +/- 1.9, 31.1 +/- 2.0, 33.9 +/- 1.9 versus 22.5 +/- 1.1, P < 0.05). While the elevation values of EF and FS began to reduce in group I 14 days after, it continued to increase in both group II and group III. Absolute value of LVEDP at 21 days after treatment was increased in group I, group II and group III compared to group IV (5.3 mm Hg +/- 1.2 mm Hg, 6.0 +/- 1.3 mm Hg, 6.2 mm Hg +/- 1.2 mm Hg versus 1.5 mm Hg +/- 0.2 mm Hg, P < 0.05), as well as absolute value of DP/dtmin (4756 mm Hg/s +/- 270 mm Hg/s, 5028 mm Hg/s +/- 253 mm Hg/s, 5283 mm Hg/s +/- 363 mm Hg/s versus 3201 mm Hg/s +/- 211 mm Hg/s, P < 0.05). DP/dtmax at 21 days after treatment increased in group I, group II and group III compared to group IV (6026 mm Hg/s +/- 281 mm Hg/s, 6278 mm Hg/s +/- 319 mm Hg/s, 7057 mm Hg/s +/- 389 mm Hg/s versus 5293 mm Hg/s +/- 360 mm Hg/s, P < 0.05). SERCA2a expressions and enzyme activity were significantly stronger in group I and group III than in group II and group IV.
It showed that all MSC transplantation, SERCA2a gene therapy and MSC-based gene therapy could enhance cardiac function. The recovered heart function continued to improve in MSC transplantation group and MSC-based gene therapy group up to 21 days, however slowed down in single gene therapy group in 21 days. Such therapeutic tendency of MSC-based gene therapy was stronger than that of MSC transplantation. Thus, MSC proved an effective platform for the targeted delivery of therapeutic gene.