Cardiac progenitor cells identification and isolation using aptamers

• Grant number: 11/19678-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2012
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: José Eduardo Krieger
• Grantee: Vinícius Bassaneze
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther, AP.TEM

Abstract

Alternatives for ischemic myocardium treatment have been the subject of intense research in recent years and cell therapy is a great promise in the area. Our laboratory has pursued this goal using adult stem cells from different origins and evidences suggests that the benefits on the reduction of post-infarction cardiac deterioration are resulted from formation of new vessels and immunomodulation due to cytokines secreted, rather than generation of new cardiomyocytes (CMs), that would be highly desirable. The generation of iPS made possible to obtain cells similar to embryonic stem cells, but patient specific and with a high capacity of differentiation. From these cells is possible to be obtained cardiac progenitor cells (CPCs), interesting for myocardial repair therapy, since are able to generate CMs.Moreover, it was recently discovered that hearts of one-day mice can regenerate after partial surgical resection, as well as new CMs are generated in adult hearts after myocardial infarction, particularly when animals are treated with thymosin ²4 for seven days before the infarction. The identification of CPCs in both embryonic and adult is traditionally done using known intracellular markers of cardiac development (transcription factors, such as Nkx2.5 genes or the contractile machinery), and only a few surface molecules (Flk-1, c-kit, MDR-1 and Sca-1), but not truly specific. The identification of specific surface markers will be essential to implement strategies for purification of cardiac progenitors, which are in few numbers. The technique for discovering new ligands from whole cells, Cell-SELEX can be used for this purpose. Through it, aptamers can be selected for their affinity to bind to specific molecules of heart precursors. In this context, the objective of this work is to select aptamers that can specifically recognize the membrane signature of heart progenitor cells and distinguish it from other cell types present in the heart. In addition, the tool that will be developed is potentially patentable and can be used to identify future targets which are specifically recognized. Once validated, we will already have the ligands for the enrichment of the population by MACS or FACS, analysis by high throughput techniques and its subsequent clinical use.

Scientific publications

(4)

(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)

TEOFILO SATURI DE CARVALHO, ANA ELISA; BASSANEZE, VINICIUS; FORNI, MARIA FERNANDA; KEUSSEYAN, ALINE ALFONSO; KOWALTOWSKI, ALICIA JULIANA; KRIEGER, JOSE EDUARDO. Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism. SCIENTIFIC REPORTS, v. 7, NOV 13 2017. (12/10109-7, 13/17368-0, 13/04871-6, 13/26440-7, 11/19678-1, 15/25776-7, 13/07937-8)

BLOISE, ANTONIO CARLOS; DOS SANTOS, JENNIFER ADRIANE; DE BRITO, ISIS VASCONCELOS; BASSANEZE, VINICIUS; GOMES, LIGIA FERREIRA; ALENCAR, ADRIANO MESQUITA. Discriminating aspects of global metabolism of neonatal cardiomyocytes from wild type and KO-CSRP3 rats using proton magnetic resonance spectroscopy of culture media samples. IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, SEP 2020. (14/22102-2, 11/19678-1, 18/20910-5, 13/17368-0, 14/21646-9)

JENSEN, LEONARDO; NERI, ELIDA; BASSANEZE, VINICIUS; DE ALMEIDA OLIVEIRA, NATHALIA C.; DARIOLLI, RAFAEL; TURACA, LAURO T.; LEVY, DEBORA; VERONEZ, DOUGLAS; FERRAZ, MARIANA S. A.; ALENCAR, ADRIANO M.; et al. Integrated molecular, biochemical, and physiological assessment unravels key extraction method mediated influences on rat neonatal cardiomyocytes. Journal of Cellular Physiology, v. 233, n. 7, p. 5420-5430, JUL 2018. (16/50439-7, 13/17368-0, 11/19678-1, 15/50216-5)

BLOISE, ANTONIO CARLOS; DOS SANTOS, JENNIFER ADRIANE; DE BRITO, ISIS VASCONCELOS; BASSANEZE, VINICIUS; GOMES, LIGIA FERREIRA; ALENCAR, ADRIANO MESQUITA. Discriminating aspects of global metabolism of neonatal cardiomyocytes from wild type and KO-CSRP3 rats using proton magnetic resonance spectroscopy of culture media samples. IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, v. 56, n. 8, p. 10-pg., 2020-09-10. (14/22102-2, 14/21646-9, 18/20910-5, 11/19678-1, 13/17368-0)