Key result
Direct co-culture allowing cell-to-cell contact between MSCs and cardiac myofibroblasts yielded the most prominent anti-fibrosis effects compared to paracrine approaches.
Why the study?
Does direct co-culture with MSCs improve anti-fibrosis effects in cardiac myofibroblasts compared to paracrine approaches?
Does direct co-culture with MSCs improve anti-fibrosis effects in cardiac myofibroblasts compared to paracrine approaches?
Direct cell-to-cell contact between MSCs and cardiac myofibroblasts provides superior anti-fibrotic effects compared to paracrine mechanisms alone, highlighting a key mechanism for MSC therapy in cardiac fibrosis.
Does not support clinical MSC use in cardiac fibrosis; leaves open contact-dependent mechanisms for human translation.
The onset of cardiac fibrosis post myocardial infarction greatly impairs the function of heart. Recent advances of cell transplantation showed great benefits to restore myocardial function, among which the mesenchymal stem cells (MSCs) has gained much attention. However, the underlying cellular mechanisms of MSC therapy are still not fully understood. Although paracrine effects of MSCs on residual cardiomyocytes have been discussed, the amelioration of fibrosis was rarely studied as the hostile environment cannot support the survival of most cell populations and impairs the diffusion of soluble factors. Here in order to decipher the potential mechanism of MSC therapy for cardiac fibrosis, we investigated the interplay between MSCs and cardiac myofibroblasts (mFBs) using interactive co-culture method, with comparison to paracrine approaches, namely treatment by MSC conditioned medium and gap co-culture method. Various fibrotic features of mFBs were analyzed and the most prominent anti-fibrosis effects were always obtained using direct co-culture that allowed cell-to-cell contacts. Hepatocyte growth factor (HGF), a well-known anti-fibrosis factor, was demonstrated to be a major contributor for MSCs' anti-fibrosis function. Moreover, physical contacts and tube-like structures between MSCs and mFBs were observed by live cell imaging and TEM which demonstrate the direct cellular interactions.
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Li et al. (2015) studied Cardiac fibrosis post myocardial infarction. Direct co-culture of MSCs and cardiac myofibroblasts vs. MSC conditioned medium and gap co-culture was evaluated on Fibrotic features of cardiac myofibroblasts. Direct co-culture allowing cell-to-cell contact between MSCs and cardiac myofibroblasts yielded the most prominent anti-fibrosis effects compared to paracrine approaches.
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