Molecular and functional characterization of CD133+ stem/progenitor cells infused in patients with end-stage liver disease reveals their interplay with stromal liver cells
| Autor: | Pietro Andreone, Paolo Caraceni, Rossella Manfredini, Licia Foscoli, Tiziana Montemurro, Rosaria Giordano, Elisa Bianchi, Ferdinando Giannone, Antonia D'Errico, Valeria Giudice, Antonio Curti, Maurizio Baldassarre, Marilena Ciciarello, Daria Sollazzo, Chiara Antoniani, Lucia Catani, Roberto M. Lemoli, Elisa Montelatici |
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| Přispěvatelé: | Catani, Lucia, Sollazzo, Daria, Bianchi, Elisa, Ciciarello, Marilena, Antoniani, Chiara, Foscoli, Licia, Caraceni, Paolo, Giannone, Ferdinando Antonino, Baldassarre, Maurizio, Giordano, Rosaria, Montemurro, Tiziana, Montelatici, Elisa, D'Errico, Antonia, Andreone, Pietro, Giudice, Valeria, Curti, Antonio, Manfredini, Rossella, Lemoli, Roberto Massimo |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Cancer Research end-stage liver disease Immunology Biology CD133+stem/progenitor cells cell therapy liver microenvironment Immunology and Allergy Oncology Genetics (clinical) Cell Biology Transplantation Cell therapy CD133+ stem/progenitor cells End Stage Liver Disease 03 medical and health sciences 0302 clinical medicine Granulocyte Colony-Stimulating Factor medicine Hepatic Stellate Cells Humans AC133 Antigen Progenitor cell Physiologic Neovascularization Cell Proliferation Stem Cells CD133+stem/progenitor cell Coculture Techniques Endothelial stem cell Haematopoiesis 030104 developmental biology medicine.anatomical_structure Liver Hepatic stellate cell 030211 gastroenterology & hepatology Liver function Bone marrow Neovascularization Physiologic Stem Cell Transplantation Stromal Cells Stem cell |
| Popis: | Background aims Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133+ stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. Methods Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133+ cell therapy. Next, we set up an in vitro model mimicking SPCs/liver microenvironment interaction by culturing granulocyte colony-stimulating factor (G-CSF)-mobilized CD133+and LX-2 hepatic stellate cells. Results We found that patients with ESLD show normal basal levels of circulating hematopoietic and endothelial progenitors with impaired clonogenic ability. After G-CSF treatment, patients with ESLD were capable to mobilize significant numbers of functional multipotent SPCs, and interestingly, this was associated with increased levels of selected cytokines potentially facilitating SPC function. Co-culture experiments showed, at the molecular and functional levels, the bi-directional cross-talk between CD133+ SPCs and human hepatic stellate cells LX-2. Human hepatic stellate cells LX-2 showed reduced activation and fibrotic potential. In turn, hepatic stellate cells enhanced the proliferation and survival of CD133+ SPCs as well as their endothelial and hematopoietic function while promoting an anti-inflammatory profile. Discussion We demonstrated that the interaction between CD133+ SPCs from patients with ESLD and hepatic stellate cells induces significant functional changes in both cellular types that may be instrumental for the improvement of liver function in cirrhotic patients undergoing cell therapy. |
| Databáze: | OpenAIRE |
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