Characterization of a mesenchymal stem cell line that differentiates to bone and provides niches supporting mouse and human hematopoietic stem cells

Abstract

Identification of mouse cell lines with properties of primary multipotential mesenchymal stromal cells (MSC) is required to facilitate the use of mouse models for evaluation of mechanisms in bone formation, hematopoiesis and cellular therapies for regenerative medicine. Primary murine MSC vary between strains, are difficult to grow in vitro and have inconsistent properties. The main aim of the study was to establish OMA-AD cells as an appropriate model system to conduct studies on MSC, bone formation and hematopoiesis. OMA-AD cells were isolated by differential trypsinization of C57BL/6J mouse bone marrow (BM) cells. The cells were then repassaged, cloned and characterized. OMA-AD cells were immortal and non-tumorigenic, differentiated readily to all mesenchymal cell types including bone, supported mouse and human hematopoiesis and were immunosuppressive. Our results demonstrated that OMA-AD cells possessed the properties of primary MSC. In addition, these cells grew readily and consistently, thereby facilitating future studies of bone formation, hematopoiesis and mesenchymal cells for regenerative medicine

Multipotentialmesenchymal Stromal Cells (MMSC) Ameliorate Graft versus Host Disease (GVHD) in a Mouse Model, But Major Suppression of GVHD Permits Leukemic Relapse

“…A primary property of these cells is their ability to form clonal colonies of cells in vitro (fibroblast colony forming cells, FCFC, or colony forming cells fibroblast, CFC-F). In addition, these cells exhibit multipotential differentiation under different culture conditions to fibroblasts, chondrocytes, osteoblasts and adipocytes [19] [20]. Owen and Friedenstein [21] provided a summary of the biology of these cells in a CIBA Foundation Symposium and coined the term marrow stromal cells (MSC).…”

“…A subcommittee of the International Society for Cellular Therapy described the properties of these cells and recommended they be termed multipotential mesenchymal stromal cells (MMSC) and this terminology is adopted for this study [25]. MMSC can be obtained from bone marrow [20], liposuction aspirates [26]- [28], Wharton's jelly, placenta [29] [30] and potentially other tissues and appear related to pericytes of blood vessels [31] [32]. The extent of differences based on tissue of origin requires further evaluation [33].…”

“…One problem is that primary mouse MMSC differ between strains [87], and can be difficult to grow and are variable in morphology and properties depending on the culture conditions [88] [89]. This suggested that use of an appropriate MMSC line [20] with more consistent properties might offer advantages in experimental systems. Such an approach would offer advantages of consistency, economy, and regulatory efficiency in clinical applications.…”

“…In an attempt to resolve these controversies, the objective of this research was to develop, evaluate and validate a basic mouse model using strain combinations not previously evaluated [12] to investigate the ability of MMSC including a cloned MMSC line [20] to ameliorate acute GVHD, to examine effects on major immune cell types and determine if this therapy compromised allograft versus leukemia cell therapeutic benefits.…”

Increased osteogenesis with hydroxyapatite constructs combined with serially-passaged bone marrow-derived mesenchymal stem cells

“…Bone marrow-derived MSCs (BMSCs) have the potential for self-renewal and differentiation into several cell types after culture expansion in vitro and in vivo, including osteoblastic, chondrocytic, adipocytic and neuronal cells [3][4][5][6][7]. Differentiation into osteoblastic lineage cells after subculture in osteogenic-induced media, containing dexamethasone (Dex), ascorbic acid phosphate and β-glycerophosphate (β-GP), has been shown for rat and human BMSCs [8][9][10][11].…”