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Mesenchymal stromal cells (MSCs) induce ex vivo proliferation and erythroid commitment of cord blood haematopoietic stem cells (CB-CD34+ cells).
Perucca, Simone; Di Palma, Andrea; Piccaluga, Pier Paolo; Gemelli, Claudia; Zoratti, Elisa; Bassi, Giulio; Giacopuzzi, Edoardo; Lojacono, Andrea; Borsani, Giuseppe; Tagliafico, Enrico; Scupoli, Maria Teresa; Bernardi, Simona; Zanaglio, Camilla; Cattina, Federica; Cancelli, Valeria; Malagola, Michele; Krampera, Mauro; Marini, Mirella; Almici, Camillo; Ferrari, Sergio; Russo, Domenico.
Afiliación
  • Perucca S; Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Di Palma A; Laboratorio CREA (Centro di Ricerca Emato-oncologica AIL), ASST Spedali Civili of Brescia, Brescia, Italy.
  • Piccaluga PP; Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Gemelli C; Laboratorio CREA (Centro di Ricerca Emato-oncologica AIL), ASST Spedali Civili of Brescia, Brescia, Italy.
  • Zoratti E; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
  • Bassi G; Section of Genomics and Personalized Medicine, Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
  • Giacopuzzi E; Parco Scientifico e Tecnologico Materiali Innovativi e Ricerca Applicata del Mirandolese, Modena, Italy.
  • Lojacono A; Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy.
  • Borsani G; Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.
  • Tagliafico E; Unit of Biology and Genetics, Department of Molecular and Translational Medicine (DMTM), University of Brescia, Brescia, Italy.
  • Scupoli MT; U.O. of Obstetrics and Gynecology I, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Bernardi S; Unit of Biology and Genetics, Department of Molecular and Translational Medicine (DMTM), University of Brescia, Brescia, Italy.
  • Zanaglio C; Centro di Ricerche Genomiche, Dipartimento di Scienze della Vita, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.
  • Cattina F; Interdepartmental Laboratory of Medical Research (LURM), University of Verona, Verona, Italy.
  • Cancelli V; Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Malagola M; Laboratorio CREA (Centro di Ricerca Emato-oncologica AIL), ASST Spedali Civili of Brescia, Brescia, Italy.
  • Krampera M; Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Marini M; Laboratorio CREA (Centro di Ricerca Emato-oncologica AIL), ASST Spedali Civili of Brescia, Brescia, Italy.
  • Almici C; Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Ferrari S; Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Russo D; Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
PLoS One ; 12(2): e0172430, 2017.
Article en En | MEDLINE | ID: mdl-28231331
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Células Eritroides / Sangre Fetal / Células Madre Mesenquimatosas Límite: Adult / Female / Humans / Male Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Células Eritroides / Sangre Fetal / Células Madre Mesenquimatosas Límite: Adult / Female / Humans / Male Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos