Targeting of human CD34(+) hematopoietic stem cells with myosin light chain preserves cardiac function in chronic infarcted mouse heart

Abstract

Background We demonstrated that transplantation of the engineered CD 34(+) hematopoietic stem cells [CD34(+)HSC] mitigates cardiac function loss in damaged mouse hearts. Objective: To determine 1) if targeted arming CD34(+)HSC with bivalent antibodies directed against myosin light chain (MLC) antigen increases its homing in myocardial infarction (MI); 2) if engineered CD34(+)HSC mitigates functional loss in mouse MI. Methods: MI was created by ligation of the left descending artery in adult mice. After 48 hr, animals were divided into 3 groups: 1) MI (n = 4): animals received RPMI medium; 2) MI + CD34(+)HSC (n = 7): animals received 5x105 CD34(+)HSC; 3) Sham (n = 4): animals underwent thoractomy without MI. Two weeks later, cardiac contractility was measured in Langendorff model. Immunohistochemistry (IHS) was used to monitor the homing of armed CD34+HSC. Results: MI heart exhibited enlarged chamber diameters and a decrease in contractility comparedwith sham hearts. IHS demonstrated an accumulation of CD34+HSC in MI hearts. Engraftment of CD34+HSC increased left ventricular developed pressure (Sham/MI/CD34(+)HSC = 95 ± 1/58 ± 12/99 ± 5 mmHg, *p<0.05), rate pressure product (Sham/MI/CD34(+)HSC = 44 ± 3 x10−3/24 ± 5 x10−3/43 ± 5 x10−3 mmHg.beats/min, *p<0.05), heart rate (Sham/MI/CD34(+)HSC = 475 ± 36 /405 ± 32/432 ± 33 beats/min). Conclusion: Targeted arming of CD34+HSC with MLC results in an increase in contractility in post MI heart. The protective effects of CD34(+)HSC in MI is associated with an increase in accumulation of engineered CD34+HSC in MI hearts. (NIH 1 P20 RR018728)