Abstract

Mesenchymal stromal cells (MSCs) were obtained from human bone marrow and amplified in cultures supplemented with human platelet lysate. Once semi-confluent, cells were seeded in solid collagen scaffolds that were rapidly colonized by the cells generating a 3D cell scaffold. Here, they acquired a myofibroblast phenotype and when exposed to appropriate chemical stimulus, developed tension and cell shortening, similar to those of striated and smooth muscle cells. Myofibroblasts contained a molecular motor—the non-muscle myosin type IIA (NMMIIA) whose crossbridge (CB) kinetics are dramatically slow compared with striated and smooth muscle myosins. Huxley’s equations were used to determine the molecular mechanical properties of NMMIIA. Thank to the great number of NMMIIA molecules, we determined the statistical mechanics (SM) of MSCs, using the grand canonical ensemble which made it possible to calculate various thermodynamic entities such as the chemical affinity, statistical entropy, internal energy, thermodynamic flow, thermodynamic force, and entropy production rate. The linear relationship observed between the thermodynamic force and the thermodynamic flow allowed to establish that MSC-laden in collagen scaffolds were in a near-equilibrium stationary state (affinity ≪ RT), MSCs were also seeded in solid collagen scaffolds functionalized with the tripeptide Arg-Gly-Asp (RGD). This induced major changes in NMMIIA SM particularly by increasing the rate of entropy production. In conclusion, collagen scaffolds laden with MSCs can be viewed as a non-muscle contractile bioengineered tissue operating in a near-equilibrium linear regime, whose SM could be substantially modified by the RGD peptide.

Highlights

  • Several “non-muscle” native tissues, including the placenta and the skin or pathological or bioengineered tissues can develop shortening and/or tension under specific circumstances when they are stimulated by an electrical field or KCl in vitro

  • We showed that the bioengineered tissue we generated exhibited a near-equilibrium thermodynamic status associated with a linear stationary state

  • Human Mesenchymal stromal cells (MSCs) seeded in collagen scaffolds used in this study represent an engineered tissue with contractile properties that were close to those of the human placenta

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Summary

Introduction

Several “non-muscle” native tissues, including the placenta and the skin or pathological or bioengineered tissues can develop shortening and/or tension under specific circumstances when they are stimulated by an electrical field or KCl in vitro. Most of these “non-muscle” structures can be native, bioengineered or pathological tissues. Myofibroblasts have been discovered in the skin by Gabbiani et al [1]. These cells are involved in wound healing contraction secondary to their active retraction in the granulation tissue [2].

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