title: Anti-inflammatory/tissue repair macrophages enhance the cartilage-forming capacity of human bone marrow-derived mesenchymal stromal cells.
abstract: Macrophages are key players in healing processes. However, little is known on their capacity to modulate the differentiation potential of mesenchymal stem/stromal cells (MSC). Here we investigated whether macrophages (Mf) with, respectively, pro-inflammatory and tissue-remodeling traits differentially modulate chondrogenesis of bone marrow derived-MSC (BM-MSC). We demonstrated that coculture in collagen scaffolds of BM-MSC with Mf derived from monocytes polarized with M-CSF (M-Mf), but not with GM-CSF (GM-Mf) resulted in significantly higher glycosaminoglycan (GAG) content than what would be expected from an equal number of BM-MSC alone (defined as chondro-induction). Moreover, type II collagen was expressed at significantly higher levels in BM-MSC/M-Mf as compared to BM-MSC/GM-Mf constructs, while type X collagen expression was unaffected. In order to understand the possible cellular mechanism accounting for chondro-induction, developing monoculture and coculture tissues were digested and the properties of the isolated BM-MSC analysed. We observed that as compared to monocultures, in coculture with M-Mf, BM-MSC decreased less markedly in number and exhibited higher clonogenic and chondrogenic capacity. Despite their chondro-inductive effect in vitro, M-Mf did not modulate the cartilage tissue maturation in subcutaneous pockets of nude mice, as evidenced by similar accumulation of type X collagen and calcified tissue. Our results demonstrate that coculture of BM-MSC with M-Mf results in synergistic cartilage tissue formation in vitro. Such effect seems to result from the survival of BM-MSC with high chondrogenic capacity. Studies in an orthotopic in vivo model are necessary to assess the clinical relevance of our findings in the context of cartilage repair.
authors.affiliation: Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Pediatric Surgery, University Children's Hospital of Basel (UKBB), Basel, Switzerland.
authors.forename: Sergio B
authors.initials: SB
authors.lastname: Sesia
authors.forename: Ralph
authors.initials: R
authors.lastname: Duhr
authors.forename: Carolina
authors.initials: C
authors.lastname: Medeiros da Cunha
authors.forename: Atanas
authors.initials: A
authors.lastname: Todorov
authors.forename: Stefan
authors.initials: S
authors.lastname: Schaeren
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Padovan
authors.forename: Giulio
authors.initials: G
authors.lastname: Spagnoli
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.forename: Andrea
authors.initials: A
authors.lastname: Barbero
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002356:Cartilage / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D014945:Wound Healing / Q000502:physiology*; D055815:Young Adult
chemical_list: D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003094:Collagen