National Grants
Grant no: PN-III-P1-1.1-TE-2021-1344, Contract No. contract: 149/2022, the period of development: 09/06/2022-07/06/2024
Acronim: FibroTher
Title: Enhancing the paracrine properties of fibroblasts by three-dimensional aggregation for chronic wounds therapy
Project director: ROSCA ANA-MARIA
Abstract: Mesenchymal stromal cells (MSC) are important for the regenerative therapy of chronic wounds, due to their secretory activity, giving rise to the concept of “cell-free therapeutic strategy. Recent studies and our results have shown that fibroblasts (Fb) are phenotypically identical with MSC and they are able to aggregate into spheroids and change their secretome as a result. Fb use a special type of cell activation named nemosis in order to enhance their secretory capabilities. Thus, the purpose of this project is to establish Fb as alternative source for the “cell-free” regenerative therapy for chronic wounds by enhancing their therapeutic paracrine properties via 3D culture-induced nemosis. In order to achieve this goal, we propose five objectives: 1) in vitro evaluation of the wound healing properties of Fb-derived spheroids secretome, 2) Assessment of the pro-angiogenic properties induced by 3D aggregation in Fb, 3) Assessment of the anti-inflammatory properties induced by 3D aggregation in Fb, 4) Validation of the pro-healing effects of the secretome of Fb-derived spheroids on excisional wounds in murine animal model and 5) management and dissemination. We expect to: establish a new source for regenerative therapy, bring new insights into the biology of Fb by clarifying the importance of nemosis in the 3D cultures and to introduce new approaches for advancing the “cell-free therapeutic strategies” for chronic wounds therapy.
Objective: to establish fibroblasts as alternative source for cell-free regenerative therapy with application in chronic wound healing by enhancing their therapeutic paracrine properties via 3D aggregation.
Expected results: establish a new source for regenerative therapy, bring new insights into the biology of Fb by clarifying the importance of nemosis in the 3D cultures and to introduce new approaches for advancing the “cell-free therapeutic strategies” for chronic wounds therapy.
Budget: 450.000 lei
TEAM:
Ana Maria Rosca, PhD- project director
Irina Titorencu, postdoctoral researcher
Raluca Tutuianu, postdoctoral researcher
Vasile Pruna, PhD, postdoctoral researcher
Daniela Madalina Ghetu (Iacomi), PhD student
DISSEMINATION 2022
Scientific paper:Iacomi DM, Rosca AM, Tutuianu R, Neagu TP, Pruna V, Simionescu M, Titorencu I. Generation of an immortalized human adipose-derived mesenchymal stromal cell line suitable for wound healing therapy. Int J Mol Sci. 2022 Aug 10;23(16):8925. doi: 10.3390/ijms23168925. PMID: 36012192; PMCID: PMC9408591. (IF = 6.208).
Prezentare orala: Daniela Madalina Ghetu (Iacomi), Rosca AM, Tutuianu R, Neagu TP, Pruna V, Simionescu M, Titorencu I. Aggregates of dermal fibroblasts and bone marrow mesenchymal stromal cells exhibit different characteristics: implications for regenerative therapy; „International Conference and XXXIX Scientific Session of the Romanian Society of Cell Biology”, 21-23 octombrie, Cluj, Romania.