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Abstract

Myocardial infarction represents one of the leading causes of mortality and morbidity worldwide. From a medical point of view, its management remains imperfect and only allows a slowing down of the disease's course. Based on preclinical results and lessons learned from the first human clinical trials, the cell therapy approach represents a promising therapeutic proposal. However, weak viability and short-term engraftment were recorded when corresponding human cells were evaluated in clinical trials, highly limiting the structural and functional benefits of their administration in infarcted heart.

The general objective of the project was to define if hMuStem cells can be implanted in infarct heart, interact with cardiac tissue cells and positively impact on function.

To do this, an infarction induction protocol was performed on an immunodeficient rat model followed by a xenotransplantation protocol. Histologically, a reduced myocardial fibrosis and an increased angiogenesis were observed three weeks post-transplantation. It was associated with skeletal and cardiac muscle fiber formation in the infarct site. A large proportion of engrafted cells adopted a reserve cell position in the conjunctive matrix. On a functional level, an attenuation of the left ventricle dilatation and a significant preservation of the contractile function have been highlighted.

Overall, our results suggest that intramyocardial transplantation of hMuStem cells could represent a suitable strategy for the treatment of myocardial infarction.

Thesis supervisors: Laétitia Guével, Flavien Charpentier

Partners: 

• Institut du Thorax, INSERM, CNRS, UNIV Nantes, Nantes;
• UMR 1064/Core Facility TRIP/Nantes Université, CHU, INSERM UMS 016, CNRS UMS 3556, Nantes.

Associated publication:

• Rannou A, Toumaniantz G, Larcher T, Leroux I, Ledevin M, Hivonnait A, Babarit C, Fleurisson R, Dubreil L, Ménoret S, Anegon I, Charpentier F, Rouger K, Guével L. Human MuStem Cell Grafting into Infarcted Rat Heart Attenuates Adverse Tissue Remodeling and Preserves Cardiac Function. Mol Ther Methods Clin Dev. 2020 Jun 15;18:446-463. doi: 10.1016/j.omtm.2020.06.009.

2016-2019