Reactivating endogenous mechanisms of cardiac regeneration via paracrine boosting using the human amniotic fluid stem cell secretome.

Authors:
Carolina Balbi
Carolina Balbi
Regenerative Medicine Laboratory
Winston-Salem | United States
Silvia Moimas
Silvia Moimas
University of Messina Medical School
Italy
Francesco Moccia
Francesco Moccia
University of Pavia
Vittorio Rosti
Vittorio Rosti
Center for the Study of Myelofibrosis
Francesca Campagnoli
Francesca Campagnoli
Regenerative Medicine Laboratory

Int J Cardiol 2019 Jul 4;287:87-95. Epub 2019 Apr 4.

Regenerative Medicine Laboratory, Department of Experimental Medicine, University of Genova, Genova, Italy. Electronic address:

Background: The adult mammalian heart retains residual regenerative capability via endogenous cardiac progenitor cell (CPC) activation and cardiomyocyte proliferation. We previously reported the paracrine cardioprotective capacity of human amniotic fluid-derived stem cells (hAFS) following ischemia or cardiotoxicity. Here we analyse the potential of hAFS secretome fractions for cardiac regeneration and future clinical translation.

Methods: hAFS were isolated from amniotic fluid leftover samples from prenatal screening. hAFS conditioned medium (hAFS-CM) was obtained following hypoxic preconditioning. Anti-apoptotic, angiogenic and proliferative effects were evaluated on rodent neonatal cardiomyocytes (r/mNVCM), human endothelial colony forming cells (hECFC) and human CPC. Mice undergoing myocardial infarction (MI) were treated with hAFS-CM, hAFS-extracellular vesicles (hAFS-EV), or EV-depleted hAFS-CM (hAFS-DM) by single intra-myocardial administration and evaluated in the short and long term.

Results: hAFS-CM improved mNVCM survival under oxidative and hypoxic damage, induced Ca-dependent angiogenesis in hECFC and triggered hCPC and rNVCM proliferation. hAFS-CM treatment after MI counteracted scarring, supported cardiac function, angiogenesis and cardiomyocyte cell cycle progression in the long term. hAFS-DM had no effect. hAFS-CM and hAFS-EV equally induced epicardium WT1+ CPC reactivation. Although no CPC cardiovascular differentiation was observed, our data suggests contribution to local angiogenesis by paracrine modulation. hAFS-EV alone were able to recapitulate all the beneficial effects exerted by hAFS-CM, except for stimulation of vessel formation.

Conclusions: hAFS-CM and hAFS-EV can improve cardiac repair and trigger cardiac regeneration via paracrine modulation of endogenous mechanisms. While both formulations are effective in sustaining myocardial renewal, hAFS-CM retains higher pro-angiogenic potential, while hAFS-EV particularly enhances cardiac function.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2019.04.011DOI Listing
July 2019
3 Reads

Publication Analysis

Top Keywords

cardiac regeneration
12
hafs-cm
9
regeneration paracrine
8
hafs-cm hafs-ev
8
paracrine modulation
8
cardiac function
8
human amniotic
8
amniotic fluid
8
endogenous mechanisms
8
cardiac
7
hafs-ev
5
improved mnvcm
4
mnvcm survival
4
survival oxidative
4
oxidative hypoxic
4
administration evaluated
4
hafs-cm improved
4
long termresults
4
short long
4
supported cardiac
4

Similar Publications