title: Mesenchymal stromal cells (MSCs) induce ex vivo proliferation and erythroid commitment of cord blood haematopoietic stem cells (CB-CD34+ cells).
abstract: A human bone marrow-derived mesenchymal stromal cell (MSCs) and cord blood-derived CD34+ stem cell co-culture system was set up in order to evaluate the proliferative and differentiative effects induced by MSCs on CD34+ stem cells, and the reciprocal influences on gene expression profiles. After 10 days of co-culture, non-adherent (SN-fraction) and adherent (AD-fraction) CD34+ stem cells were collected and analysed separately. In the presence of MSCs, a significant increase in CD34+ cell number was observed (fold increase = 14.68), mostly in the SN-fraction (fold increase = 13.20). This was combined with a significant increase in CD34+ cell differentiation towards the BFU-E colonies and with a decrease in the CFU-GM. These observations were confirmed by microarray analysis. Through gene set enrichment analysis (GSEA), we noted a significant enrichment in genes involved in heme metabolism (e.g. LAMP2, CLCN3, BMP2K), mitotic spindle formation and proliferation (e.g. PALLD, SOS1, CCNA1) and TGF-beta signalling (e.g. ID1) and a down-modulation of genes participating in myeloid and lymphoid differentiation (e.g. PCGF2) in the co-cultured CD34+ stem cells. On the other hand, a significant enrichment in genes involved in oxygen-level response (e.g. TNFAIP3, SLC2A3, KLF6) and angiogenesis (e.g. VEGFA, IGF1, ID1) was found in the co-cultured MSCs. Taken together, our results suggest that MSCs can exert a priming effect on CD34+ stem cells, regulating their proliferation and erythroid differentiation. In turn, CD34+ stem cells seem to be able to polarise the BM-niche towards the vascular compartment by modulating molecular pathways related to hypoxia and angiogenesis.
authors.affiliation: Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.|Laboratorio CREA (Centro di Ricerca Emato-oncologica AIL), ASST Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Perucca
authors.affiliation: Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.|Laboratorio CREA (Centro di Ricerca Emato-oncologica AIL), ASST Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Palma
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.|Section of Genomics and Personalized Medicine, Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.affiliation: Parco Scientifico e Tecnologico Materiali Innovativi e Ricerca Applicata del Mirandolese, Modena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gemelli
authors.affiliation: Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zoratti
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Bassi
authors.affiliation: Unit of Biology and Genetics, Department of Molecular and Translational Medicine (DMTM), University of Brescia, Brescia, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Giacopuzzi
authors.affiliation: U.O. of Obstetrics and Gynecology I, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lojacono
authors.affiliation: Unit of Biology and Genetics, Department of Molecular and Translational Medicine (DMTM), University of Brescia, Brescia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borsani
authors.affiliation: Centro di Ricerche Genomiche, Dipartimento di Scienze della Vita, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Tagliafico
authors.affiliation: Interdepartmental Laboratory of Medical Research (LURM), University of Verona, Verona, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Scupoli
authors.affiliation: Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.|Laboratorio CREA (Centro di Ricerca Emato-oncologica AIL), ASST Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bernardi
authors.affiliation: Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.|Laboratorio CREA (Centro di Ricerca Emato-oncologica AIL), ASST Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Zanaglio
authors.affiliation: Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cattina
authors.affiliation: Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cancelli
authors.affiliation: Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Malagola
authors.affiliation: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Krampera
authors.affiliation: Department of Transfusion Medicine, Laboratory for Stem Cells Manipulation and Cryopreservation, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Marini
authors.affiliation: Department of Transfusion Medicine, Laboratory for Stem Cells Manipulation and Cryopreservation, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Almici
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D018952:Antigens, CD34 / Q000032:analysis; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34