Where Ideas Grow

Stem Cells in Regenerative Biology and Repair

ABOUT

We investigate the genesis, maintenance and response to injury of the heart and the hematopoietic system to decipher biological mechanisms that promote organ functional recovery upon tissue damage. By working in these two systems, closely related in ontogeny and yet so distinctive in their premises (stem cell-based hematopoiesis vs. stem cell-devoid cardiogenesis), we aim to disclose the role of stem cells in homeostasis and in response to disease or trauma.

 

RESEARCH

The heart and the hematopoietic system share the origin in mesodermal precursors during embryo development. However, while the hematopoietic system renews through life to meet the demands for very high number of cells in the blood, cellular turnover in the heart is low and damaged cardiomyocytes are not replaced. This transduces in high regenerative capacity for hematopoiesis, whilst low cardiomyocyte turnover results in repair mechanisms (fibrosis) and cardiac dysfunction.
The main questions currently under investigation are:

  • What are the mechanisms controlling the loss of regenerative capacity of the heart after birth? We have previously shown the neonatal heart is able to elicit both regenerative and reparative (fibrosis) responses. We are dissecting these mechanisms toward their therapeutic application in the adult heart;
  • Why cardiomyocytes stop diving through development? We have identified cell-surface markers of developing cardiomyocytes endowed with division capacity. Of note, these cardiomyocytes persist in low numbers in the adult and are poised for activation after injury. We are investigating the dynamics of this particular population;
  • What are the conditions for the physiological expansion of hematopoietic stem cells (HSC) in fetal liver? Carrying on evidence indicating that a cell non-autonomous mechanism regulates the renewal of lines of hematopoietic stem/progenitor cells of embryonic and adult derivation, we are dissecting the microenvironment of the fetal liver to capture the signals that distinguish a niche where HSC expand.

We use an integrative approach that combines advanced in vitro cellular systems, genetic/injury animal models, organ decellularization and state-of-the-art molecular/cellular analysis to generate basic knowledge to apply in the development of new bioengineered regenerative strategies targeted to the heart and blood.

 

Depth colour-coded stack of a E14.5 foetal liver's thick section staining haematopoietic cell

Team

Selected Publications

Perestrelo A.R., Silva A.C., Oliver-De La Cruz J., Martino F., Horváth V., Caluori G., Polanský O., Vinarský V., Azzato G., De Marco G., Žampachová V., Skládal P., Pagliari S., Rainer A., Pinto-Do-Ó P., Caravella A., Koci K., Nascimento D.S., Forte G.,
Multiscale Analysis of Extracellular Matrix Remodeling in the Failing Heart. Circulation Research:24-38, 2021. [Journal: Article] [CI: 9] [IF: 17,4 (*)]
DOI: 10.1161/CIRCRESAHA.120.317685 SCOPUS: 85098106406

Silva A.C., Pereira C., Fonseca A.C.R.G., Pinto-do-Ó P., Nascimento D.S.,
Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response. Frontiers in Cell and Developmental Biology8:, 2021. [Journal: Review] [CI: 16] [IF: 6,7 (*)]
DOI: 10.3389/fcell.2020.621644 SCOPUS: 85100007243

Soares-da-Silva F., Peixoto M., Cumano A., Pinto-do-Ó P.,
Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development. Frontiers in Cell and Developmental Biology8:, 2020. [Journal: Review] [CI: 1] [IF: 6.7]
DOI: 10.3389/fcell.2020.00612 SCOPUS: 85089081037

Valente M., Resende T.P., Nascimento D.S., Burlen-Defranoux O., Soares-Da-Silva F., Dupont B., Cumano A., Pinto-Do-ó P.,
Mouse HSA+ immature cardiomyocytes persist in the adult heart and expand after ischemic injury. PLoS Biology17(6):, 2019. [Journal: Article] [CI: 3] [IF: 7,1]
DOI: 10.1371/journal.pbio.3000335 SCOPUS: 85069625001

Sampaio-Pinto V., Rodrigues S.C., Laundos T.L., Silva E.D., Vasques-Nóvoa F., Silva A.C., Cerqueira R.J., Resende T.P., Pianca N., Leite-Moreira A., D'Uva G., Thorsteinsdóttir S., Pinto-do-Ó P., Nascimento D.S.,
Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis. Stem Cell Reports10(3):860-874, 2018. [Journal: Article] [CI: 18] [IF: 5,5]
DOI: 10.1016/j.stemcr.2018.01.042 SCOPUS: 85042586130

Freire A.G., Waghray A., Soares-da-Silva F., Resende T.P., Lee D.F., Pereira C.F., Nascimento D.S., Lemischka I.R., Pinto-do-Ó P.,
Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate. Stem Cell Reports9(1):136-148, 2017. [Journal: Article] [CI: 3] [IF: 6,5]
DOI: 10.1016/j.stemcr.2017.05.025 SCOPUS: 85021126795

Silva A.C., Rodrigues S.C., Caldeira J., Nunes A.M., Sampaio-Pinto V., Resende T.P., Oliveira M.J., Barbosa M.A., Thorsteinsdóttir S., Nascimento D.S., Pinto-do-Ó P.,
Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult. Biomaterials104:52-64, 2016. [Journal: Article] [CI: 35] [IF: 8,4]
DOI: 10.1016/j.biomaterials.2016.06.062 SCOPUS: 84978822623

Valente M., Nascimento D.S., Cumano A., Pinto-Do-Ó P.,
Sca-1+cardiac progenitor cells and heart-making: A critical synopsis. Stem Cells and Development23(19):2263-2273, 2014. [Journal: Review] [CI: 38] [IF: 3,7]
DOI: 10.1089/scd.2014.0197 SCOPUS: 84907432293

Nascimento D.S., Valente M., Esteves T., de Fátima de Pina M., Guedes J.G., Freire A., Quelhas P., Pinto-do-Ó P.,
MIQuant - semi-automation of infarct size assessment in models of cardiac ischemic injury. PLoS ONE6(9):, 2011. [Journal: Article] [CI: 30] [IF: 4,1]
DOI: 10.1371/journal.pone.0025045 SCOPUS: 80053583980