title: Stem Cell Spheroids and Ex Vivo Niche Modeling: Rationalization and Scaling-Up.
abstract: Improved protocols/devices for in vitro culture of 3D cell spheroids may provide essential cues for proper growth and differentiation of stem/progenitor cells (S/PCs) in their niche, allowing preservation of specific features, such as multi-lineage potential and paracrine activity. Several platforms have been employed to replicate these conditions and to generate S/PC spheroids for therapeutic applications. However, they incompletely reproduce the niche environment, with partial loss of its highly regulated network, with additional hurdles in the field of cardiac biology, due to debated resident S/PCs therapeutic potential and clinical translation. In this contribution, the essential niche conditions (metabolic, geometric, mechanical) that allow S/PCs maintenance/commitment will be discussed. In particular, we will focus on both existing bioreactor-based platforms for the culture of S/PC as spheroids, and on possible criteria for the scaling-up of niche-like spheroids, which could be envisaged as promising tools for personalized cardiac regenerative medicine, as well as for high-throughput drug screening.
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Rome, Italy.
authors.forename: Isotta
authors.initials: I
authors.lastname: Chimenti
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Massai
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Morbiducci
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Antonio Paolo
authors.initials: AP
authors.lastname: Beltrami
authors.affiliation: Tissue Engineering Research Unit, "Centro Cardiologico Monzino", IRCCS, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pesce
authors.affiliation: Department of Pediatrics and Infant Neuropsychiatry, "Umberto I" Hospital, "La Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy. elisa.messina@uniroma1.it.
authors.forename: Elisa
authors.identifier: http://orcid.org/0000-0002-1654-9001
authors.initials: E
authors.lastname: Messina
mesh_terms: D000818:Animals; D020811:Biomedical Technology / Q000295:instrumentation / Q000379:methods*; D019149:Bioreactors; D002450:Cell Communication; D018929:Cell Culture Techniques / Q000295:instrumentation; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D004734:Energy Metabolism; D006801:Humans; D010641:Phenotype; D044968:Regenerative Medicine / Q000295:instrumentation / Q000379:methods*; D018874:Spheroids, Cellular; D055153:Stem Cell Niche; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*
keywords: Bioreactors; Cardiospheres; Cell spheroids; Scaling-up; Stem cell niche