Immunological and Functional Characterization of Multipotent Mesenchymal Stromal Cells in Myeloproliferative Neoplasms

• Grant number: 18/01756-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2018
• End date: August 31, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Fabíola Attié de Castro
• Grantee: Maira da Costa Cacemiro
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Myeloproliferative neoplasms (MPN) are hematological disorders characterized by increased cell proliferation and accumulation of mature and precursor myeloid cells in peripheral blood independently of cytokine stimuli and growth factors.The discovery of genetic mutations since 2005 has contributed to the elucidation of the physiopathology of MPN. However, despite the knowledge accumulated in the last decade, there is still a need to elucidate the cellular and molecular mechanisms that contribute to the appearance and progression of this group of diseases, including alterations of the hematopoietic niche.Although dysregulated hematopoiesis present in MPN is mainly attributed to molecular changes in the hematopoietic stem cell (HSC), the abnormality of the medullary microenvironment seems to be important in the development of these diseases. The stromal microenvironment of the bone marrow is composed of extracellular matrix and specialized cells, with emphasis on the mesenchymal stromal cells (MSC) that guarantee the maintenance of the potential for self-renewal and pool of HTC. MSC contribute to the quiescence of HSC, protecting them from pro-apoptotic stimuli and differentiation. In addition to genetic alterations in HSC and changes in the microenvironment, it is also considered that MPN are onco-inflammatory diseases and are characterized by abnormal activity of the immune system.Therefore, our hypothesis is that alterations in the immunomodulatory profile of MSC, as well as structural or expression changes of components of the hematopoietic marrow niche contribute to the physiopathology of MPN. We believe that MSC can modulate the hematopoietic niche by means of cytokines, lipid mediators and growth factors, capable of altering the functioning and structure of the medullary microenvironment, favoring the neo-angiogenesis and proliferation of neoplastic myeloid cells.The present project will evaluate the immunomodulatory potential of the multipotent mesenchymal stromal cells of MPN aiming to establish the relationship between the alteration of the hematopoietic microenvironment and the physiopathology of MPN.

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE ALMEIDA, FELIPE CAMPOS; BERZOTI-COELHO, MARIA G.; TORO, DIANA MOTA; CACEMIRO, MAIRA DA COSTA; BASSAN, VITOR LEONARDO; BARRETTO, GABRIEL DESSOTTI; MARQUES GARIBALDI, PEDRO MANOEL; PALMA, LEONARDO CARVALHO; DE FIGUEIREDO-PONTES, LORENA LOBO; SORGI, CARLOS ARTERIO; et al. Bioactive Lipids as Chronic Myeloid Leukemia's Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors. FRONTIERS IN IMMUNOLOGY, v. 13, p. 8-pg., 2022-04-13. (14/50947-7, 15/21866-1, 18/19714-7, 15/23555-3, 15/00658-1, 13/08135-2, 18/01756-5)

GOMES PEREIRA, ILLY ENNE; CACEMIRO, MAIRA DA COSTA; COMINAL, JUCARA GASTALDI; BARRETTO, GABRIEL DESSOTTI; DE CASTRO, FABIOLA ATTIE. Role of Endothelial Cells in Hematological Malignancies. EURASIAN JOURNAL OF MEDICINE AND ONCOLOGY, v. 6, n. 3, p. 9-pg., 2022-01-01. (13/08135-2, 18/19714-7, 18/01756-5, 14/50947-7)

COMINAL, JUCARA GASTALDI; CACEMIRO, MAIRA DA COSTA; PINTO-SIMOES, BELINDA; KOLB, HANS-JOCHEM; RIBEIRO MALMEGRIM, KELEN CRISTINA; DE CASTRO, FABIOLA ATTIE. Emerging Role of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Pathogenesis of Haematological Malignancies. STEM CELLS INTERNATIONAL, v. 2019, p. 12-pg., 2019-01-01. (13/08135-2, 18/19714-7, 18/01756-5, 14/50947-7)

SANDRA MARA BURIN; MAIRA DA COSTA CACEMIRO; JUÇARA GASTALDI COMINAL; RONE APARECIDO DE GRANDIS; ANA RITA THOMAZELA MACHADO; FLAVIA SACILOTTO DONAIRES; ADELIA CRISTINA OLIVEIRA CINTRA; LUCIANA AMBROSIO; LUSÂNIA MARIA GREGGI ANTUNES; SUELY VILELA SAMPAIO; et al. Bothrops moojeni L-amino acid oxidase induces apoptosis and epigenetic modulation on Bcr-Abl+ cells. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020-12-14. (18/01756-5, 15/25637-7, 11/23236-4)

COMINAL, JUCARA GASTALDI; CACEMIRO, MAIRA DA COSTA; PINTO-SIMOES, BELINDA; KOLB, HANS-JOCHEM; RIBEIRO MALMEGRIM, KELEN CRISTINA; DE CASTRO, FABIOLA ATTIE. Emerging Role of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Pathogenesis of Haematological Malignancies. STEM CELLS INTERNATIONAL, 2019. (13/08135-2, 14/50947-7, 18/19714-7, 18/01756-5)

COMINAL, JUCARA GASTALDI; CACEMIRO, MAIRA DA COSTA; BERZOTI-COELHO, MARIA GABRIELA; PEREIRA, ILLY ENNE GOMES; FRANTZ, FABIANI GAI; SOUTO, ELIZABETH XISTO; COVAS, DIMAS TADEU; FIGUEIREDO-PONTES, LORENA LOBO DE; OLIVEIRA, MARIA CAROLINA; MALMEGRIM, KELEN CRISTINA RIBEIRO; et al. Bone Marrow Soluble Mediator Signatures of Patients With Philadelphia Chromosome-Negative Myeloproliferative Neoplasms. FRONTIERS IN ONCOLOGY, v. 11, MAY 18 2021. (13/08135-2, 14/50947-7, 18/01756-5, 18/19714-7, 15/23555-3)

BURIN, SANDRA MARA; CACEMIRO, MAIRA COSTA; COMINAL, JUCARA GASTALDI; DE GRANDIS, RONE APARECIDO; THOMAZELA MACHADO, ANA RITA; DONAIRES, FLAVIA SACILOTTO; OLIVEIRA CINTRA, ADELIA CRISTINA; AMBROSIO, LUCIANA; GREGGI ANTUNES, LUSANIA MARIA; SAMPAIO, SUELY VILELA; et al. Bothrops moojeni L-amino acid oxidase induces apoptosis and epigenetic modulation on Bcr-Abl plus cells. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, DEC 14 2020. (15/25637-7, 11/23236-4, 18/01756-5)

CACEMIRO, MAIRA DA COSTA; COMINAL, JUCARA GASTALDI; BERZOTI-COELHO, MARIA GABRIELA; TOGNON, RAQUEL; NUNES, NATALIA DE SOUZA; SIMOES, BELINDA; PEREIRA, ITALO SOUSA; CARLOS, DANIELA; FACCIOLI, LUCIA HELENA; DE FIGUEIREDO-PONTES, LORENA LOBO; et al. Differential cytokine network profile in polycythemia vera and secondary polycythemia. SCIENTIFIC REPORTS, v. 10, n. 1, APR 27 2020. (15/23555-3, 17/23501-6, 18/01756-5, 14/50947-7, 18/19714-7, 13/08135-2)