Monitoring of diffusion properties and transverse relaxation time of mouse ischaemic muscle after administration of human mesenchymal stromal cells derived from adipose tissue.

Agnieszka Skorupa,Ewelina Pilny,Ryszard Smolarczyk,Łukasz Boguszewicz,Mateusz Ciszek,Stanisław Szala,Łukasz Krakowczyk,Tomasz Cichoń,Magdalena Jarosz–Biej,Maria Sokół

doi:10.1111/cpr.12672

Abstract

ObjectivesApplication of non‐invasive imaging methods plays an important role in the assessment of cellular therapy effects in peripheral artery disease. The purpose of this work was to evaluate the kinetics of MRI‐derived parameters characterizing ischaemic hindlimb muscle after administration of human mesenchymal stromal cells derived from adipose tissue (hADSC) in mice.Materials and methodsMRI experiments were performed on a 9.4T Bruker system. The measurement protocol included transverse relaxation time mapping and diffusion tensor imaging. The monitoring period encompassed 14 days after femoral artery ligation and subsequent cell administration. The effect of hADSC transplantation was compared with the effect of normal human dermal fibroblasts (NHDFs) and phosphate‐buffered saline injection.ResultsThe most significant differences between the hADSC group and the remaining ones were observed around day 3 after ischaemia induction (increased transverse relaxation time in the hADSC group in comparison with the control group) and around day 7 (increased transverse relaxation time and decreased third eigenvalue of the diffusion tensor in the hADSC group in comparison with the control and NHDF groups) at the site of hADSC injection. Histologically, it was associated with increased macrophage infiltration at days 3‐7 and with the presence of small regenerating fibres in the ischaemic tissue at day 7.ConclusionsOur results underscore the important role of macrophages in mediating the therapeutic effects of hADSCs and confirm the huge potential of magnetic resonance imaging in monitoring of cellular therapy effects.

Highlights

IntroductionFrom 3% to 10% of the population in the Western world suffer from peripheral arterial disease, and this represents a major health problem of ageing population
From 3% to 10% of the population in the Western world suffer from peripheral arterial disease, and this represents a major health problem of ageing population.The natural response to major artery occlusion is a complex process, which can be divided into three phases: (a) cell necrosis and apoptosis phase caused by hypoxia; (b) inflammatory phase characterized by lymphocyte, monocyte and neutrophil migration into the damaged tissue for removal of dead cells; and (c) the muscle regeneration phase.[1]
Since many studies indicate that mesenchymal stromal cells (MSCs) and fibroblasts are indistinguishable from each other,[34] we focused on the ischaemic tissue response to human normal human dermal fibroblasts (NHDFs) cells

Summary

Introduction

From 3% to 10% of the population in the Western world suffer from peripheral arterial disease, and this represents a major health problem of ageing population. The natural response to major artery occlusion is a complex process, which can be divided into three phases (with some overlapping): (a) cell necrosis and apoptosis phase caused by hypoxia; (b) inflammatory phase characterized by lymphocyte, monocyte and neutrophil migration into the damaged tissue for removal of dead cells; and (c) the muscle regeneration phase.[1] During this process, vasculogenesis, angiogenesis and arteriogenesis occur to establish a functional vascular network. Skeletal muscle has the ability to recover after ischaemic injury. Post‐ ischaemic vessel growth and remodelling processes are markedly impaired in patients suffering from arterial diseases. The prevalence of this condition is approximately 1.3%.3 new therapeutic approaches for these patients are being searched

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