Hyaluronan coating improves liver engraftment of transplanted human biliary tree stem/progenitor cells.
Cell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver.



We developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo.



The HA coating markedly improved the viability, colony formation, and population doubling of hBTSCs in primary cultures, and resulted in a higher expression of integrins that mediate cell attachment to matrix components. When HA-coated hBTSCs were transplanted via the spleen into the liver of immunocompromised mice, the engraftment efficiency increased to 11% with respect to 3% of uncoated cells. Notably, HA-coated hBTSC transplantation in mice resulted in a 10-fold increase of human albumin gene expression in the liver and in a 2-fold increase of human albumin serum levels with respect to uncoated cells. Studies in distant organs showed minimal ectopic cell distribution without differences between HA-coated and uncoated hBTSCs and, specifically, cell seeding in the kidney was excluded.



A ready and economical procedure of HA cell coating greatly enhanced the liver engraftment of transplanted hBTSCs and improved their differentiation toward mature hepatocytes. HA coating could improve outcomes of stem cell therapies of liver diseases and could be immediately translated into the clinic given that GMP-grade HAs are already available for clinical use.
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Lorenzo
L
Nevi
Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome, Italy.
Guido
G
Carpino
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Daniele
D
Costantini
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Vincenzo
V
Cardinale
Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
Olga
O
Riccioni
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Sabina
S
Di Matteo
Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy.
Fabio
F
Melandro
Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy.
Pasquale Bartolomeo
PB
Berloco
Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Lola
L
Reid
Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy. eugenio.gaudio@uniroma1.it.|Division of Human Anatomy, Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Via Borelli 50, 00161, Rome, Italy. eugenio.gaudio@uniroma1.it.
Eugenio
E
Gaudio
Department of Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. domenico.alvaro@uniroma1.it.|Division of Gastroenterology, Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University of Rome, Vialedell'Università 37, 00185, Rome, Italy. domenico.alvaro@uniroma1.it.
Domenico
D
Alvaro
D000328:Adult; D000368:Aged; D001659:Biliary Tract / Q000166:cytology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D009928:Organ Specificity; D013154:Spleen / Q000166:cytology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D055815:Young Adult
D015815:Cell Adhesion Molecules; D020099:Coated Materials, Biocompatible; D006820:Hyaluronic Acid
Adult stem cells; Cell transplantation; Hepatocyte differentiation; Hyaluronan; Liver