title: Angiogenic and anti-inflammatory properties of mesenchymal stem cells from cord blood: soluble factors and extracellular vesicles for cell regeneration.
abstract: In a recent work, our group showed the existence of two distinct mesenchymal stem cell (MSC) subsets within human umbilical cord blood. One less proliferative and short-living (SL-CBMSC), the other with higher growth rate and long-living (LL-CBMSC), and therefore better suited for regenerative medicine applications. We examined whether LL-CBMSC possess peculiar paracrine properties able to affect angiogenesis or inflammatory processes. It was shown for the first time that pro-angiogenic, proliferation-stimulating and tissue repairing factors were released at high level not only as soluble cytokines, but also as mRNA precursors embedded in membrane vesicles. The combination of this primary (proteic factors interacting with surface receptors) and delayed (mRNA transferred and translated via vesicle fusion and cargo release) interaction in endothelial target cells resulted in strong blood vessel induction with the development of capillary-like structures. In addition, LL-CBMSC dynamically modulated their release of pro-angiogenic and anti-inflammatory factors in an in vitro model of damage. In conclusion, LL-CBMSC synthesize and secrete multiple factors that may be attuned in response to the status of the target cell, a crucial requisite when paracrine mechanisms are needed at onset of tissue regeneration.
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Montemurro
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Mariele
authors.initials: M
authors.lastname: Viganò
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ragni
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Barilani
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Parazzi
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Boldrin
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lavazza
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Montelatici
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Banfi
authors.affiliation: Anatomia Patologica, Ospedale Sacco, Università degli Studi di Milano, Milano, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lauri
authors.affiliation: Milano Cord Blood Bank, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giovanelli
authors.affiliation: Laboratorio Citogenetica e Genetica molecolare, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Baccarin
authors.affiliation: Laboratorio Citogenetica e Genetica molecolare, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Guerneri
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Giordano
authors.affiliation: Unit of Cell Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy. Electronic address: lorenza.lazzari@policlinico.mi.it.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Lazzari
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D000067128:Extracellular Vesicles / Q000378:metabolism / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007231:Infant, Newborn; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D044968:Regenerative Medicine
keywords: Angiogenesis; Cord blood; Extracellular vesicles; Growth factors; Human mesenchymal stem cells; miRNA