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.
Dissemination 2023:
Capitol de carte
Rosca, AM., Tutuianu, R., Ghetu, D.M., Titorencu, I. (2023). Mesenchymal Stromal Cells for Wound Healing Therapy: From Expectations to Reality. In: Haider, K.H. (eds) Handbook of Stem Cell Applications. Springer, Singapore. https://doi.org/10.1007/978-981-99-0846-2_53-1.
Lucrari ISI
Tudoroiu EE, Albu Kaya MG, Titorencu I, Dinu-Pîrvu CE, Marin MM, Roșca Am, Popa L, Anuța V, Antoniac A, Chelaru C, Kaya DA, Prisada RM, Ghica MV. (2023) Design and evaluation of new wound dressings based on collagen-cellulose derivatives, Materials & Design, 236: 112469, https://doi.org/10.1016/j.matdes.2023.112469.
Luca I., Albu Kaya M.G., Titorencu I., Dinu-Pîrvu C.E., Marin M.M., Popa L., Roșca AM., Antoniac A., Anuța V., Ghica M.V., Physico-chemical characterization and biocompatibility evaluation of some vaginal formulations based on collagen and mucoadhesive polymers, in revizie -Materials Today Chemistry, factor impact 7.3
Poster
Raluca Tutuianu, Ana-Maria Rosca, Daniela Madalina Ghetu, Vasile Pruna, Madalina Albu Kaya. „Evaluation of mesenchymal cells-derived products as therapeutics for skin regeneration”. Poster prezentat la manifestatia stiintifica “1st NETSKINMODELS Network event” organizata la Bratislava, Slovacia, 14-18 februarie 2023.
Prezentare orala
Irina Titorencu. “MSC based therapy for diabetic chronic wounds”. Prezentare in manifestatiei stiintifica “1st NETSKINMODELS Network event” organizata la Bratislava, Slovacia, 14-18 februarie 2023.
Dissemination 2024:
Lucrări ISI
Luca I., Albu Kaya M.G., Titorencu I., Dinu-Pîrvu C.E., Marin M.M., Popa L., Roșca AM., Antoniac A., Anuța V., Ghica M.V., Physico-chemical characterization and biocompatibility evaluation of some vaginal formulations based on collagen and mucoadhesive polymers, in revizie
Elena Dănilă, Mădălina Georgiana Albu Kaya, Minodora Maria Marin, Irina Titorencu, Ana-Maria Rosca, Alina Elena Coman and Rodica Roxana Constantinescu. Extraction and characterization of fish collagen hydrogel from northern pike (Esox lucius) with potential application in skin wound healing– manuscris in preparare.
Daniela Madalina Ghetu (Iacomi), Raluca Tutuianu, Maya Simionescu, Irina Titorencu, Ana Maria Rosca. Three-dimensional organization of human dermal fibroblasts enhances their paracrine role in skin wound healing - manuscris in preparare;
Daniela Madalina Ghetu (Iacomi), Raluca Tutuianu, Maya Simionescu, Irina Titorencu, Ana Maria Rosca. The secretome of human dermal fibroblasts spheroids supports skin regeneration by promoting the remodeling of the extracellular matrix on a full thickness wound mouse model - manuscris in preparare.
Poster
Raluca Tutuianu, Daniela Madalina Ghetu, Irina Titorencu, Ana Maria Rosca. Mediul conditionat derivat de la fibroblaste cultivate in sferoizi promoveaza regenerarea pielii pe un model murin de rana cutanata; Poster prezentat la manifestatia stiintifica Simpozionul ARSAL 2024 ,, Evaluarea severității și conceptul 3R in proiectele ce folosesc animale în experimentare”, 29 martie 2024, organizat de Asociaţia Română pentru Ştiinţa Animalelor de Laborator, gazduita de Institutul Național de Cercetare-Dezvoltare în Domeniul Patologiei și Științelor Biomedicale "Victor Babeș".
RAPORT STIINTIFIC FINAL 