title: Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells.
abstract: Umbilical cord blood (UCB) transplantation and haematological recovery are currently limited by the amount of haematopoietic progenitor cells (HPCs) present in each unit. HPCs and haematopoietic stem cells (HSCs) normally interact with cells and extracellular matrix (ECM) proteins present within the endosteal and vascular niches. Hence, we investigated whether coating of culture surfaces with ECM proteins normally present in the marrow microenvironment could benefit the ex vivo expansion of HPCs. Towards this, collagen types I and IV (COL I and IV), laminin (LN) and fibronectin (FN) were tested individually or as component of two ECM-mix complexes. Individually, ECM proteins had both common and unique properties on the growth and differentiation of UCB CD34+ cells; some ECM proteins favoured the differentiation of some lineages over that of others (e.g. FN for erythroids), some the expansion of HPCs (e.g. LN and megakaryocyte (MK) progenitor) while others had less effects. Next, two ECM-mix complexes were tested; the first one contained all four ECM proteins (4ECMp), while the second 'basement membrane-like structure' was without COL I (3ECMp). Removal of COL I led to strong reductions in cell growth and HPCs expansion. Interestingly, the 4ECMp-mix complex reproducibly increased CD34+ (1.3-fold) and CD41+ (1.2-fold) cell expansions at day 6 (P < 0.05) versus control, and induced greater myeloid progenitor expansion (P < 0.05) than 3ECMp. In conclusion, these results suggest that optimization of BM ECM protein complexes could provide a better environment for the ex vivo expansion of haematopoietic progenitors than individual ECM protein.
authors.affiliation: Hema-Quebec, Research & Development Department, Quebec City, PQ, Canada.
authors.forename: Betül
authors.initials: B
authors.lastname: Celebi
authors.forename: Diego
authors.initials: D
authors.lastname: Mantovani
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pineault
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism / Q000494:pharmacology; D024141:Collagen Type IV / Q000378:metabolism / Q000494:pharmacology; D003470:Culture Media; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D008422:Materials Testing; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D024042:Collagen Type I; D024141:Collagen Type IV; D003470:Culture Media; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D007797:Laminin