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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.