Abstract 14867: Wnt11 Over-expressing Mesenchymal Stem Cells Promote Cardiomyocyte Proliferation by Paracrine Signaling
Objective: The regenerative capacity of the heart is very limited and consequently, the heart cannot regenerate adequately after injury. Our previous studies showed that the paracrine factors released from mesenchymal stem cells (MSCs) overexpressing Wnt11 protected cardiomyocytes (CM) after myocardial infarction. Here, we hypothesized that these factors also stimulate CM proliferation.
Methods and Results: MSCs harvested from rat bone marrow were transduced with Wnt11 (MSCWnt11) or EGFP empty vector (MSCGFP). Conditioned medium (CdM ) were obtained from MSCGFP (CdMGFP) or MSCWnt11 (CdMWnt11) under normal and hypoxic culture for 36 hours. CM obtained from neonatal and adult rat ventricles were cultured in CdMGFP, CdMWnt11 or CdMWnt11-H medium for 3 and 7 days. Cultured CM were stained with BrdU, Ki67, and Aurora B, respectively and identified by staining with α-actinin. Some CM were positive for these proliferative markers (Fig. 1). The expression of proliferating cell nuclear antigen (PCNA), cyclin D2, Nkx2.5, b-myosin heavy chain (b-MHC), atrial natriuretic factor (ANF), troponin I type 1 (Tnni1), troponin I type 3 (Tnni3), sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA2), and desmin was analysed (Fig. 2). Although PCNA was downregulated in CM treated with CdM, other cardiac specific markers were significantly upregulated in CM treated with CdMWnt11 or CdMWnt11-Hobtained from MSCWnt11 exposed to hypoxia for 24 hours. Moreover, CdMWnt11 also increased adult CM mitosis, cytokinesis, and CM numbers compared to CdMGFP. In addition, CdM significantly improved the contractile dyskinesis of adult CM caused by 7 days culture in non-serum M199 medium (Fig. 3).
Conclusions: Our studies support the hypothesis that paracrine factors released from MSC promote CM re-entry cell-cycle and proliferation. Wnt11 may serve as a positive regulator of CM proliferation.
Author Disclosures: J. Wang: None. H. Liu: None. B. Yu: None. M. Gong: None. Y. Wang: None. M. Ashraf: None. M. Xu: None.
- © 2014 by American Heart Association, Inc.