Dynamic secretome of bone marrow-derived stromal cells reveals a cardioprotective biochemical cocktail

Abstract

Transplanted stromal cells have demonstrated considerable promise as therapeutic agents in diverse disease settings. Paracrine signaling can be an important mediator of these therapeutic effects at the sites of acute or persistent injury and inflammation. As many stromal cell types, including bone marrow-derived stromal cells (BMSCs), display tissue-specific responses, there is a need to explore their secretory dynamics in the context of tissue and injury type. Paracrine signals are not static, and could encode contextual dynamics in the kinetic changes of the concentrations of the secreted ligands. However, precise measurement of dynamic and context-specific cellular secretory signatures, particularly in adherent cells, remains challenging. Here, by creating an experimental and computational analysis platform, we reconstructed dynamic secretory signatures of cells based on a very limited number of time points. By using this approach, we demonstrate that the secretory signatures of CD133-positive BMSCs are uniquely defined by distinct biological contexts, including signals from injured cardiac cells undergoing oxidative stress, characteristic of cardiac infarction. Furthermore, we show that the mixture of recombinant factors reproducing the dynamics of BMSC-generated secretion can mediate a highly effective rescue of cells injured by oxidative stress and an improved cardiac output. These results support the importance of the dynamic multifactorial paracrine signals in mediating remedial effects of stromal stem cells, and pave the way for stem cell-inspired cell-free treatments of cardiac and other injuries.

SDF-1α Gene-Activated Collagen Scaffold Restores Pro-Angiogenic Wound Healing Features in Human Diabetic Adipose-Derived Stem Cells

“…However, it did not compromise the signaling of the anti-angiogenic tissue inhibitors, which are essential for tissue remodeling [ 57 , 67 , 68 , 70 ]. It has been observed that stem cells possess a unique ability to sense external stimuli and accordingly modulate their secretome to offer a cytoprotective effect [ 86 ]. In our study, the modulatory impact of the SDF-1α gene-activated scaffold in the ADSCs appears to be controlled by the receptor CXCR7 ( Figure 2 C).…”

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

“…These processes are likely to act on RNA‐dependent and RNA‐independent elements of FUS‐related pathology . Transplanted bone marrow derived stem cells were shown to secrete such anti‐inflammatory cytokines and growth factors, as IL‐10, vascular endothelial growth factor (VEGF), insulin‐like growth factor‐1 (IGF‐1), hepatocyte growth factor (HGF), brain‐derived neurotrophic factor (BDNF), neuronal growth factor (NGF), and others . This secretion was shown to be condition‐dependent, and in particular, the presence of inflammation was found to stimulate the release of the anti‐inflammatory molecules .…”

Stem cell secretome as a new booster for regenerative medicine

“…Other work by Kshitiz et al reinforced the idea that secretome of bone marrow-derived stromal cells revealed a cardioprotective biochemical cocktail (36). In this study, researchers reconstructed dynamic secretory signatures of cells based on a very limited number of time points.…”