Co-SuSTaIn

Project PN-III-P2-2.1-PED-2016-1881: Consolidating the Subcutaneous Transplantation of Mesenchymal Stem Cells as a Warranted Therapy for Myocardial Infarction

Numar Contract: 251PED/2017

Acronym: Co-SuSTaIn

Coordinator: Dr. Mihai Bogdan Preda

Budget: 450.000 Lei

Period: September 2017 - December 2018

Co-Sustain aims to refine and consolidate the strategy for subcutanous (s.c.) transplantation of mesenchymal stem cells (MSCs) as a warranted therapy for myocardial infarction (MI).

The goals of the project are: (i) To determine the number of human MSCs in a transplantation dose that produces maximum benefits to the infarcted heart; (ii) To assess the extra-benefits produced by a repetitive dose of s.c. transplanted MSCs on the cardiac function after myocardial infarction; (iii) To evaluate the effectiveness of allogenic MSCs in conferring cardioprotection by s.c. transplantation after myocardial infarction.

This project started from research ideas, hypotheses, experimental designs and proof-of-concepts demonstrated in laboratory (that have reached TRL 3 to date) that were consolidated and standardized during its implementation. Extensive analysis, research and data collection have been performed in vivo with human cells in order to validate the concepts and to design the proper technologies for achieving effective intrinsic regeneration process of the myocardium after infarction (TRL 4). Besides, new advances have been made with regard to the molecular mechanisms that mediate the cardioprotection conferred by MSCs after s.c. transplantation, which might help the development of effective therapies in a broad clinical scenario.

 Schematic representation of the objectives and major project outcomes:

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Dissemination:

Publications

1. Preda MB et al. Evidence of mesenchymal stromal cell adaptation to local microenvironment following subcutaneous transplantation. J Cell Mol Med 2020; 24(18):10889-10897.

Presentations at international scientific conferences

1. M.B. Preda, S. Popescu, R. Tutuianu, A.M. Rosca, M. Simionescu, A. Burlacu. Hypoxia regulates the pro-angiogenic effect of subcutaneously transplanted mesenchymal stromal cells. Keystone Symposia meeting on Therapeutic Targeting of Hypoxia-Sensitive Pathways. 10-14.04.2018. University of Oxford Mathematical Institute, Oxford, UK (poster).

2. A. Burlacu*, M.B. Preda*, M. Fenyo, A.M. Catrina, A. Vacaru, M. Simionescu. Subcutaneous transplantation of mesenchymal stromal cells promotes reversion of hyperglycemia in streptozotocin-induced diabetic mice. Keystone Symposia meeting on Therapeutic Targeting of Hypoxia-Sensitive Pathways. 10-14.04.2018. University of Oxford Mathematical Institute, Oxford, UK (poster).

3. S Popescu, A.M. Lupan, M.B. Preda, A. Burlacu, M. Simionescu. Cross-talk between mesenchymal stromal cells and endothelial progenitors modulates the expression of angiogenesis related molecules. 06-09.07.2018. The 36th Annual Scientific Session of the Romanian Society for Cell Biology and the 10th National Congress with International participation, Craiova, Romania. (oral presentation).

4. M.B. Preda, S. Popescu, A.R. Tuchilus, A.M. Catrina, M. Ivan, M. Simionescu, A. Burlacu. Subcutaneous transplantation of mesenchymal stem cells as a warranted therapy for myocardial repair post-infarction. 15.06.2018. Oral presentation at the group seminar, Hematology Department, Indiana University School of Medicine, Indianapolis, U.S.A;

5. A. Burlacu*, M.B. Preda*, M. Fenyo, A.M. Catrina, A. Vacaru, M. Simionescu. Subcutaneous transplantation of mesenchymal stromal cells may promote reversion of hyperglycemia in responder streptozotocin-induced diabetic mice. EMBO Conference: The Molecular and Cellular Basis of Regeneration and Tissue Repair. 15-19 September 2018. Valetta, Malta (poster);

6. M.B. Preda, S. Popescu, R. Tutuianu, A.M. Rosca, M. Simionescu, A. Burlacu. Hypoxia regulates the pro-angiogenic effect of subcutaneously transplanted mesenchymal stromal cells. EMBO Conference: The Molecular and Cellular Basis of Regeneration and Tissue Repair. 15-19 September 2018. Valetta, Malta (poster).