Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue

Abstract

Stem cell based-therapies represent a possible solution to repair damaged myocardial tissue by promoting cardioprotection, angiogenesis, and reduced fibrosis. However, recent evidence indicates that most of the positive outcomes are likely due to the release of paracrine factors (cytokines, growth factors, and exosomes) from the cells and not because of the local engraftment of stem cells. This cocktail of essential growth factors and paracrine signals is known as secretome can be isolated in vitro, and the biomolecule composition can be controlled by varying stem-cell culture conditions. Here, we propose a straightforward strategy to deliver secretome produced from hASCs by using a nanocomposite injectable hydrogel made of gelatin and Laponite®. The designed secretome-loaded hydrogel represents a promising alternative to traditional stem cell therapy for the treatment of acute myocardial infarction.

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

“…MSC‐CM derived from 3D cell spheroids comprises elevated quantities of anti‐inflammatory, anti‐apoptotic, and proangiogenic factors such as TSG‐6 and stanniocalcin‐1 (STC‐1), [ 154 ] VEGF, FGF2, HGF, and Angiogenin (ANG). [ 155–157 ] This MSC spheroid‐derived CM leads to enhanced endothelial cell proliferation, migration, and tube formation [ 155,157 ] and improved functional recovery in a mouse ischemic model compared to CM derived from monocultures. [ 156 ] 3D spheroid‐derived CM also confers an anti‐inflammatory effect to macrophages, with PGE2 identified as the effector CM molecule.…”

“…[ 215 ] This biomaterial/CM combination was subsequently evaluated in an MI rat model and found to enhance angiogenesis and reduce infarct area. [ 155 ] MSC‐CM encapsulated in synthetic micro‐particles cloaked with MSC cell membrane achieved heart regeneration in a mouse MI model. [ 216 ] EV‐laden peptide hydrogels showed superior therapeutic performance compared to bolus EV injection in a rat MI model, in terms of increasing angiogenesis, and reducing fibrosis, apoptosis, and inflammation.…”

Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases

“…Significant improvement of exosome implantation on injured myocardium has been proven by that an injectable shear-thinning gel (STG) carrying EVs probably effectively improve myocardial function and increased the hemodynamics as well as the number of blood vessels . Furthermore, exosomes generated by human adipose-derived stem cells (hASCs), Gelatin and Laponite R were combined to formulate a shear-thinning, nanocomposite hydrogel (nSi Gel) which was considered as an injectable carrier of secretome (nSi Gel+), and the results indicate an increasing density of blood vessels around the myocardium, an improvement in myocardial function and a reduction in scar area (Waters et al, 2018). However, the residence time and stability of exosomes are the major challenges in the clinical application of exosomes in recent years.…”

Mesenchymal Stem/ Stromal Cells metabolomic and bioactive factors profiles: a comparative analysis on the Umbilical Cord and Dental Pulp derived Stem/ Stromal Cells secretome

“…The conditioning process was handled under serum-free conditions, so that the only factors detected in the CM were those produced by the UC-MSCs and DPSCs and not those bared to the system by exogenous supplementation. [64][65][66][67], the dental pulp and other dental tissues [61,[68][69][70][71], the umbilical cord tissue [63,72], cord blood [73], and other placental/ foetal tissues [63,74]. These works report the identification of .…”

“…It is made available under a The copyright holder for this preprint (which was this version posted August 7, 2019. . https://doi.org/10.1101/728550 doi: bioRxiv preprint most of the angiogenic factors herein investigated, such as Ang-2 [63], Endothelin-1 [65,70], FGF-2 [57-59, 63, 64, 69, 73], G-CSF [67], HB-EGF [73], HGF [59,64,65,72,73], IL-8 [57,63,68,72,74], PLGF [58] [63], VEGF [55-62, 64, 65, 68-70, 73], and TGF-β [60,64] [63].…”