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Collagen scaffold enhances the regenerative properties of mesenchymal stromal cells.

ABSTRACT: MSCs are widely applied to regenerate heart tissue in myocardial diseases but when grown in standard two-dimensional (2D) cultures exhibit limited potential for cardiac repair and develop fibrogenic features with increasing culture time. MSCs can undergo partial cardiomyogenic differentiation, which improves their cardiac repair capacity. When applied to collagen patches they may improve cardiac tissue regeneration but the mechanisms remain elusive. Here, we investigated the regenerative properties of MSCs grown in a collagen scaffold as a three-dimensional (3D) culture system, and performed functional analysis using an engineered heart tissue (EHT) model. We showed that the expression of cardiomyocyte-specific proteins by MSCs co-cultured with rat neonatal cardiomyocytes was increased in collagen patches versus conventional cultures. MSCs in 3D collagen patches were less fibrogenic, secreted more cardiotrophic factors, retained anti-apoptotic and immunomodulatory function, and responded less to TLR4 ligand lipopolysaccharide (LPS) stimulation. EHT analysis showed no effects by MSCs on cardiomyocyte function, whereas control dermal fibroblasts abrogated the beating of cardiac tissue constructs. We conclude that 3D collagen scaffold improves the cardioprotective effects of MSCs by enhancing the production of trophic factors and modifying their immune modulatory and fibrogenic phenotype. The improvement in myocardial function by MSCs after acquisition of a partial cardiac cell-like phenotype is not due to enhanced MSC contractility. A better understanding of the mechanisms of MSC-mediated tissue repair will help to further enhance the therapeutic potency of MSCs.

SUBMITTER: Rashedi I

PROVIDER: S-EPMC5663483 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Collagen scaffold enhances the regenerative properties of mesenchymal stromal cells.

Rashedi Iran I Talele Nilesh N Wang Xing-Hua XH Hinz Boris B Radisic Milica M Keating Armand A

PloS one 20171031 10

MSCs are widely applied to regenerate heart tissue in myocardial diseases but when grown in standard two-dimensional (2D) cultures exhibit limited potential for cardiac repair and develop fibrogenic features with increasing culture time. MSCs can undergo partial cardiomyogenic differentiation, which improves their cardiac repair capacity. When applied to collagen patches they may improve cardiac tissue regeneration but the mechanisms remain elusive. Here, we investigated the regenerative propert ...[more]

PMID: 29088264

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Project description:Importance:Cell therapy may be helpful for cardiac disease but has been fraught with poor cell retention and survival after transplantation. Objective:To determine whether cell-laden hydrogel treatment is safe and feasible for patients with chronic ischemic heart disease (CIHD). Design, Setting, and Participants:This randomized, double-blind clinical trial was conducted between March 1, 2016, and August 31, 2019, at a single hospital in Nanjing, China. Among 115 eligible patients with CIHD, 50 patients with left ventricular ejection fraction of 45% or less were selected to receive elective coronary artery bypass grafting (CABG) and additionally randomized to cell-plus-collagen treatment (collagen/cell group), cell treatment alone (cell group), or a control group. Sixty-five patients were excluded because of severe comorbidities or unwillingness to participate. Forty-four participants (88%) completed the study. The last patient completed 12 months of follow-up in August 2019. Analyses were prespecified and included all patients with available data. Interventions:During CABG, patients in the collagen/cell group were treated with human umbilical cord-derived mesenchymal stromal cell (hUC-MSC)-laden collagen hydrogel intramyocardial injection, and the cell group was treated with hUC-MSCs alone. Patients in the control group underwent CABG alone. Main Outcomes and Measures:The primary outcome was safety of the cell-laden collagen hydrogel assessed by the incidence of serious adverse events. The secondary end point was the efficacy of treatment, according to cardiovascular magnetic resonance imaging-based left ventricular ejection fraction and infarct size. Results:Fifty patients (mean [SD] age, 62.6 [8.3] years; 38 men [76%]) were enrolled, of whom 18 were randomized to the collagen/cell group, 17 to the cell group, and 15 to the control group. Patient characteristics did not differ among groups at baseline. For the primary end point, no significant differences in serious adverse events, myocardial damage markers, and renal or liver function were observed among all groups after treatment; the collagen/cell and cell groups each had 1 case of hospitalization because of heart failure, and no serious adverse events were seen in the control group. At 12 months after treatment, the mean infarct size percentage change was -3.1% (95% CI, -6.20% to -0.02%; P?=?.05) in the collagen/cell group, 5.19% (-1.85% to 12.22%, P?=?.35) in the cell group, and 8.59% (-3.06% to 20.25%, P?=?.21) in the control group. Conclusions and Relevance:This study provides, to our knowledge, the first clinical evidence that the use of collagen hydrogel is safe and feasible for cell delivery. These findings provide a basis for larger clinical studies. Trial Registration:ClinicalTrials.gov Identifier: NCT02635464.

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Collagen scaffold enhances the regenerative properties of mesenchymal stromal cells.

Publications

Collagen scaffold enhances the regenerative properties of mesenchymal stromal cells.

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