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NANOLIFE

                                                                          


 

 

Nr. grant: PN-III-P1-1.2-PCCDI-2017-0749, Nr. contract: 45/2018, perioada de desfasurare: 16.04.2018-30.09.2020

 

Titlu: NANOSTRUCTURI BIOACTIVE PENTRU STRATEGII TERAPEUTICE INOVATOARE (NANO-LIFE)

 

 

Proiect IBPC: Dezvoltarea unui construct de inginerie tisulară cu proprietăți antibacteriene pe bază de polimeri organici, exosomi și nanoparticule pentru tratamentul leziunilor cutanate cronice

 

Vindecarea ranilor cronice si formarea cicatricilor constituie si astazi probleme majore in tratamentul leziunilor tesuturilor moi. Este cunoscut faptul ca ranile acute si cronice prezinta o vindecare ineficienta datorata in mare parte unui proces inflamator prelungit, iar majoritatea leziunilor cronice sunt, de fapt, asociate cu ischemia, diabetul si bolile venoase. Metodele conventionale curente folosite in accelerarea procesului de vindecare si reducerea tesutului cicatricial presupun utilizarea grefelor de piele, terapiei laser precum si aplicarea locala a unor factori de crestere. In aceste conditii este nevoie de proiectarea a noi strategii si metode sigure care sa promoveze vindecarea leziunilor cornice, cu atat mai mult ca terapiile mentionate mai sus pot duce la aparitia cicatricilor atopice, a pigmentarii anormale si necrozei pielii, iar suprainfectiile reprezinta complicatii frecvente. Este cunoscut faptul ca celulele stem mezenchimale (MSC) detin un rol important in regenerarea tisulara, studii recente confirmand rolul unor vezicule eliberate de aceste cellule, exosomii (nanovezicule de 30-100 nm) in semnalizarea paracrina si efectele lor in inducerea migrarii si proliferarii fibroblastilor dermici precum si a sintezei de colagen.

In cadrul proiectului “Nanostructuri bioactive pentru strategii terapeutice inovatoare”, ne propunem utilizarea proprietatilor curative si anti-inflamatoare ale exosomilor derivati din MSC prin dezvoltarea unui construct de inginerie tisulara cu proprietati antibacteriene pe baza de polimeri organici biodegradabili (fibrina), exosomi si nanoparticule organice antibacteriene de tipul chitosanului,in vederea repararii leziunilor cutanate cronice. Pentru aceasta, MSC obtinute din lipoaspirat vor fi utilizate pentru obtinerea exosomilor cu proprietati curative. Proprietatile terapeutice ale acestor particule, cat si ale nanoparticulelor sintetice de chitosan, vor fi testate pe celule izolate din tesutul cutanat prelevat de la pacienti: keratinocite si fibroblasti.

   

 

Grant No.: PN-III-P1-1.2-PCCDI-2017-0749, Contract No.: 45/2018, period: 16.04.2018-30.09.2020

 

Title: BIOACTIVE NANOSTRUCTURES FOR INNOVATIVE THERAPEUTIC STRATEGIES (NANO-LIFE)

 

 

ICBP PARTNER PROJECT: Developing a tissue engineered construct with antibacterial properties based on organic polymers, exosomes and nanoparticles for the treatment of chronic wounds

 

 

Chronic wounds healing and scar formation represent today major problems for the treatment of soft tissue lesions. It is known that acute and chronic wounds manifest an inefficient healing caused by a prolong inflammatory phase, most of the chronic wounds being associated with ischemia, diabetes and venous disease. The routine conventional methods used in accelerating the healing process and diminishing the scar tissue formation involve skin grafts, laser therapy as well as local application of growth factors. In this context, there is a need to design new strategies and safe methods that promote the healing of chronic wounds, especially since the previous mentioned therapies can lead to atopic scar, abnormal pigmentation and skin necrosis, while infections represent frequent complications. Mesenchymal stem cel (MSC)l already have an important part in tissue regeneration, recent studies confirming the role of a subtype of vesicles released by these cell- exosomes (nanovesicles of 30-100nm) in paracrine signaling and inducing dermal fibroblasts migration and proliferation as well as collagen sinthesys.

Witihin the project “BIOACTIVE NANOSTRUCTURES FOR INNOVATIVE THERAPEUTIC STRATEGIES”, we will use the curative and anti-inflamatory properties of MSC derived exosomes by developing a tissue engineered construct with antibacterial properties based on biodegradable organic polymers (fibrin), exosomes and antibacterial organic nanoparticles (like chitosan) for the healing of chronic wounds. For this purpose, MSC derived from lipoaspirate will be used to isolated the exosomes with curative properties. The therapeutic properties of this particles, as well as those of the synthetic chitosan nanoparticles will be tested on cell isolated from human skin samplesL keratinocytes and fibroblasts.

   

Fig. 1. Principalele etape de lucru si rezultatele preconizate

Main working stages and expected results

 (marire prin click pe imagine)

Coordonator: Universitatea de Medicina si Farmacie Craiova – Prof. Dr. Laurentiu Mogoanta

Parteneri:

P1. Universitatea Politehnica Bucuresti – Dr. Alexandru Grumezescu

P2. Universitatea de Medicina si Farmacie „Carol Davila” – Prof. Dr. Ioan Lascar

P3. Institutul de Biologie si Patologie  Celulara „Nicolae Simionescu”  (IBPC - "NS")- dr. Irina Titorencu

 

 

Fig. 2. Structura organizatorica a consiliului de management

 The organizational structure of the management council

 (zoom in by clicking the image)

Coordinator: University of Medicine and Pharmacy, Craiova- Prof. Dr. Laurentiu Mogoanta

Partners:

P1. Politehnica University of Bucharest - Dr. Alexandru Grumezescu

P2. Carol Davila University of Medicine and Pharmacy- Prof. Dr. Ioan Lascar

P3. Nicolae Simionescu Institute of Cellular Biology and Pathology ("NS" -ICBP)- dr. Irina Titorencu

Echipa P3:

Dr. Irina Titorencu

Acad. Maya Simionescu

Dr. Adriana Georgescu

Dr. Ana-Maria Rosca

Dr. Vasile Pruna

Dr. Alina Constantin

Drd. Raluca Tutuianu

Tehnician Constanta Stan

Asist. Gabriela Florea – nou angajat, norma intreaga

Asist. Daniela Madalina Iacomi – nou angajat, norma intreaga

 

 

 

 


Diseminare 

Publicatii 2020

*AM Rosca, R Tutuianu, I Titorencu. Advances in Skin Regeneration and Reconstruction. In Frontiers in Stem Cell and Regenerative Medicine Research, 2020, Volume 9 9, 143-187.

*Tutuianu R, Rosca AM, Albu Kaya MG, Pruna V, Neagu TP, Lascar I, Simionescu M, Titorencu I. Mesenchymal stromal cell-derived factors promote the colonization of collagen 3D scaffolds with human skin cells. J Cell Mol Med. 2020 Jul 14, in press.

 

Diseminare 2019

Postere

Gabriela Florea, Daniela Madalina Iacomi, Raluca Tutuianu, Vasile Pruna, Ana Maria Rosca, Ioan Lascar, Maya Simionescu, Irina Titorencu. Modeling of fibroblast-to-myofibroblast differentiation in vitro, poster prezentat la manifestatia stiintifica “The 11th National Congress with International Participation and the 37th Annual Scientific Session of the Romanian Society of Cell Biology organizata la Constanta, in perioada 20-23 iunie 2019. Abstractul a fost publicat in Book of abstracts, nr. 45, pag. 69.

Daniela Madalina Iacomi, Gabriela Florea, Ana Maria Rosca, Vasile Pruna, Raluca Tutuianu, Tiberiu Paul Neagu, Irina Titorencu. Generation and characterization of an immortalized human adipose mesenchymal stromal cell line, poster prezentat la manifestatia stiintifica “The 11th National Congress with International Participation and the 37th Annual Scientific Session of the Romanian Society of Cell Biology organizata la Constanta, in perioada 20-23 iunie 2019. Abstractul a fost publicat in Book of abstracts, nr. 45, pag. 70.

Raluca Tutuianu, Ana-Maria Rosca, Alexandru Mihai Grumezescu, Alexandra Elena Stoica, Irina Titorencu. Silver-based nanoparticles preserve the properties of keratinocytes and dermal fibroblasts and can be safely used for skin wound healing, poster prezentat la manifestatia stiintifica “The 11th National Congress with International Participation and the 37th Annual Scientific Session of the Romanian Society of Cell Biology organizata la Constanta, in perioada 20-23 iunie 2019. Abstractul a fost publicat in Book of abstracts, nr. 45, pag. 131. Premiul II la sesiunea Postere

G. Florea, D. M. Iacomi, R. Tutuianu, V. Pruna, A. M. Rosca,L. Radulescu, I. Lascar, M. Simionescu, I. Titorencu,Isolation and characterization of human hypertrophic derived myofibroblasts,  poster prezentat la Simpozionul “O calatorie fascinanta de 40 ani pentru descoperirea secretelor celulei in beneficiul sanatatii omului”, Bucuresti, 19-20 septembrie.

R. Tutuianu, A.M. Rosca, V. Pruna, I. Lascar, P. Neagu, M. Simionescu, I. Titorencu, Mesenchymal stromal cells derived exosomes sustain the reepithelialization process on skin organotypic models, poster prezentat la Simpozionul “O calatorie fascinanta de 40 ani pentru descoperirea secretelor celulei in beneficiul sanatatii omului”, Bucuresti, 19-20 septembrie 2019.

 

Prezentare orala

Irina Titorencu si Maya Simionescu. Bone-marrow-derived mesenchymal stromal cells enhance the regenerative potential of skin cells, Modern Biotechnological Advances for Human Health, 28-31 mai, 2019 Bucuresti

Valorificarea cecurilor pentru imbunatatirea competentelor existente

In perioada 2-9 iulie 2019, responsabilul P3, dr. Irina Titorencu, impreuna cu cele doua persoane angajate in cadrul proiectului pe post de asistent de cercetare (Gabriela Florea si Daniela Madalina Iacomi), au efectuat un stagiu de pregatire la Facultatea de Medicina si Farmacie Craiova, in cadrul Departamentului de Cercetari Histologice al Centrului pentru Studii de Morfologie Microscopică şi Imunologie. In timpul acestui stagiu au fost aprofundate cunostintele de prelucrare si interpretare a probelor histologice.

 

Lucrari trimise spre publicare:

R. Tutuianu, A.M. Rosca, M.G. Albu Kaya, V. Pruna,T.P. Neagu, I. Lascar, M. Simionescu, I. Titorencu,Mesenchymal stromal cells-derived factors boost the colonization of collagen 3D scaffolds with human skin cells, submitted to Acta Biomaterialia, factor de impact 6.7R.

Tutuianu, G. Florea, A.M. Rosca, M. Iacomi, L. Radulescu,I. Titorencu, Isolation and characterization of myofibroblasts from hypertrophic scar, submitted to Rom J Morphol Embryol, factor de impact 1.5

 

 

 Teze de dizertatie:

Madalina Daniela Iacomi “Generarea si caracterizarea unei linii celulare imortalizate de celule stromale mezenchimale umane derivate din tesutul adipos''

Gabriela Florea ,,Efectul secretomului celulelor stromale mezenchimale umane asupra fenotipului de miofibroblast''

 

 

 

Diseminare 2018

 

Articole

Ana-Maria Rosca, Raluca Tutuianu, Ioan Lascar, Irina Domnica Titorencu. Mesenchymal stromal cells derived exosomes as tools for chronic wound healing therapy. Articol acceptat spre publicare la revista Romanian Journal of Morphology and Embryology, IF 0.912.

 

 

 

 

Prezentari orale

Ana-Maria Rosca, Raluca Tutuianu, Vasile Pruna, Irina Titorencu. Mesenchymal stromal cells derived exosomes as tools for chronic wound healing therapy. Prezentare orala la manifestatia stiintifica “The 16th National Symposium of Microscopic Morphology with International Attendance organizata la Craiova, in perioada 22-25 mai 2018. Abstract publicat in Volum de Rezumate, pag. 69.

 

Raluca Tutuianu, Ana-Maria Rosca, Madalina Albu-Kaya, Vasile Pruna, Maya Simionescu, Irina Titorencu. The secretome of mesenchymal stromal cells sustains the colonization of skin cells on collagen scaffolds. Prezentare orala la manifestatia stiintifica “Al 10-lea Congres National cu Participare Internationala si a 36-a Sesiune Stiintifica a Societatii Nationale de Biologie Celulara” organizata la Craiova, in perioada 6-9 iunie 2018. Abstract publicat in Bulletin of Romania Society for Cell Biology no. 46, Pag. 93.

 

 

Postere

Ana-Maria Rosca, Vasile Pruna, Raluca Tutuianu, T.Paul Neagu, Ioan Lascar, Maya Simionescu, Irina Titorencu. Dermal fibroblasts as new players in regenerative therapy. Poster prezentat la la manifestatia stiintifica “The 12th Central and Eastern European Proteomic Conference" 24-26 octombrie 2018, Bucuresti. Abstract publicat in Book of Abstracts pag. 108.

 

 

 

   

P3 Team:

Irina Titorencu, PhD

Acad. Maya Simionescu

Adriana Georgescu, PhD

Ana-Maria Rosca, PhD

Vasile Pruna, PhD

Alina Constantin, PhD

Raluca Tutuianu, PhD student

Constanta Stan, technician

Gabriela Florea, assistant – new employee

Daniela Madalina Iacomi, assistant – new employee

 

 

 

 


Dissemination 

Publications 2020

*AM Rosca, R Tutuianu, I Titorencu. Advances in Skin Regeneration and Reconstruction. In Frontiers in Stem Cell and Regenerative Medicine Research, 2020, Volume 9 9, 143-187.

*Tutuianu R, Rosca AM, Albu Kaya MG, Pruna V, Neagu TP, Lascar I, Simionescu M, Titorencu I. Mesenchymal stromal cell-derived factors promote the colonization of collagen 3D scaffolds with human skin cells. J Cell Mol Med. 2020 Jul 14, in press.

Dissemination 2019

Posters

Gabriela Florea, Daniela Madalina Iacomi, Raluca Tutuianu, Vasile Pruna, Ana Maria Rosca, Ioan Lascar, Maya Simionescu, Irina Titorencu. Modeling of fibroblast-to-myofibroblast differentiation in vitro, poster presented at “The 11th National Congress with International Participation and the 37th Annual Scientific Session of the Romanian Society of Cell Biology, Constanta, Romania, 20-23 June 2019. Abstract published in Book of abstracts, nr. 45, pg. 69.

Daniela Madalina Iacomi, Gabriela Florea, Ana Maria Rosca, Vasile Pruna, Raluca Tutuianu, Tiberiu Paul Neagu, Irina Titorencu. Generation and characterization of an immortalized human adipose mesenchymal stromal cell line, poster presented at “The 11th National Congress with International Participation and the 37th Annual Scientific Session of the Romanian Society of Cell Biology, Constanta, Romania, 20-23 June 2019. Abstract published in Book of abstracts, nr. 45, pg. 70.

Raluca Tutuianu, Ana-Maria Rosca, Alexandru Mihai Grumezescu, Alexandra Elena Stoica, Irina Titorencu. Silver-based nanoparticles preserve the properties of keratinocytes and dermal fibroblasts and can be safely used for skin wound healing, poster presented at “The 11th National Congress with International Participation and the 37th Annual Scientific Session of the Romanian Society of Cell Biology, Constanta, Romania, 20-23 June 2019. Abstract published in Book of abstracts, nr. 45, pg. 131. 2nd prize at the Poster Session

 G. Florea, D. M. Iacomi, R. Tutuianu, V. Pruna, A. M. Rosca,L. Radulescu, I.Lascar, M. Simionescu, I. Titorencu,Isolation and characterization of human hypertrophic derived myofibroblasts, presented atthe Simposium “An incredible 40-year journey to uncover cell’s secrets for the benefit of human health”, Bucharest,19-20 September.

R. Tutuianu, A.M. Rosca, V. Pruna, I. Lascar, P. Neagu, M. Simionescu, I. Titorencu, Mesenchymal stromal cells derived exosomes sustain the reepithelialization process on skin organotypic modelspresented atthe Simposium “An incredible 40-year journey to uncover cell’s secrets for the benefit of human health”, Bucharest,19-20 September 2019.

 

 Oral presentation

Irina Titorencu and Maya Simionescu. Bone-marrow-derived mesenchymal stromal cells enhance the regenerative potential of skin cells, Modern Biotechnological Advances for Human Health, 28-31 May, 2019 Bucharest

Making use of checks to improve existing skills

During 2-9 July 2019, Dr. Irina Titorencu, together with the new employees (Gabriela Florea si Daniela Madalina Iacomi) have completed a training course at the Faculty of Medicine and Pharmacy of Craiova, within the Department of Histological Research of the Center for Studies of Microscopic Morphology and Immunology. During this stage the knowledge of the processing and interpretation of the histological samples was deepened.

 

Papers under review:

R. Tutuianu, A.M. Rosca, M.G. Albu Kaya, V. Pruna,T.P. Neagu, I. Lascar, M. Simionescu, I. Titorencu,Mesenchymal stromal cells-derived factors boost the colonization of collagen 3D scaffolds with human skin cells, submitted to Acta Biomaterialia, impact factor 6.7

R. Tutuianu, G. Florea, A.M. Rosca, M. Iacomi, L. Radulescu,I. Titorencu, Isolation and characterization of myofibroblasts from hypertrophic scar, submitted to Rom J Morphol Embryol, impact factor 1.5

 

 

 

 

 Master thesis

Madalina Daniela Iacomi “Generation and characterization of an immortalized adipose derived human mesenchymal stromal cell line”

Gabriela Florea ,,Effect of human mesenchymal stromal cell secretome on myofibroblast phenotype''

 

 

 Dissemination 2018

Papers

Ana-Maria Rosca, Raluca Tutuianu, Ioan Lascar, Irina Domnica Titorencu. Mesenchymal stromal cells derived exosomes as tools for chronic wound healing therapy. Article accepted for publication at Romanian Journal of Morphology and Embryology, IF 0.912.

 

 

 

 

Oral presentations

Ana-Maria Rosca, Raluca Tutuianu, Vasile Pruna, Irina Titorencu. Mesenchymal stromal cells derived exosomes as tools for chronic wound healing therapy. Oral presentation at “The 16th National Symposium of Microscopic Morphology with International Attendance” organized at Craiova,  22-25 mai 2018. Abstract published in Book of abstracts, page 69.

 

Raluca Tutuianu, Ana-Maria Rosca, Madalina Albu-Kaya, Vasile Pruna, Maya Simionescu, Irina Titorencu. The secretome of mesenchymal stromal cells sustains the colonization of skin cells on collagen scaffolds. Oral presentation at “Al 10-lea Congres National cu Participare Internationala si a 36-a Sesiune Stiintifica a Societatii Nationale de Biologie Celulara” organized at Craiova, in 6-9 June 2018. Abstract published in Bulletin of Romania Society for Cell Biology no. 46, Page 93.

 

 

 Posters

Ana-Maria Rosca, Vasile Pruna, Raluca Tutuianu, T.Paul Neagu, Ioan Lascar, Maya Simionescu, Irina Titorencu. Dermal fibroblasts as new players in regenerative therapy. Poster presented at “The 12th Central and Eastern European Proteomic Conference" 24-26 October 2018, Bucharest. Abstract published in Book of Abstracts, page 108.