Sequential paracrine mechanisms are necessary for the therapeutic benefits of stem cell therapy.

Sequential paracrine mechanisms are necessary for the therapeutic benefits of stem cell therapy. Am J Physiol Cell Physiol. 2020 Oct 07;: Authors: Sun H, Pratt RE, Hodgkinson CP, Dzau VJ Abstract Stem cell injections are an attractive therapeutic tool. It has been demonstrated that injected stem cells promote tissue repair and regeneration via paracrine mechanisms. However, the effects of injected stem cells continue for far longer than they are present. We hypothesized that the effects of injected stem cells are prolonged due a sequential paracrine relay mechanism. Conditioned media was collected from mesenchymal stem cells (MSCs) after 24hr. This media was then added to RAW264.7. Media was collected from the macrophages after 24hrs and was then added to endothelial cells (ECs). This conditioned macrophage media, but not control media, promoted wound healing and induced EC differentiation. Similar results were observed with primary macrophages. To identify the active paracrine factors released by macrophages in response to stimulation by MSC conditioned media we used an antibody array; identifying increased expression of the angiogenesis-related proteins stromal cell-derived factor 1 (SDF1) and plasminogen activator inhibitor-1 (PAI-1). Knockdown of either protein inhibited the ability of conditioned media derived from MSC paracrine factor stimulated macrophages to induce EC differentiation both in vitro and in vivo. Conditioned med...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research