Three‐Dimensional Perfusion Culture of Human Bone Marrow Cells and Generation of Osteoinductive Grafts

Braccini, Alessandra; Wendt, David; Jaquiéry, Claude; Jakob, Marcel; Heberer, Michael; Kenins, Linda; Wodnar-Filipowicz, Aleksandra; Quarto, Rodolfo; Martin, Ivan

doi:10.1634/stemcells.2005-0002

Cited by 188 publications

(193 citation statements)

References 34 publications

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“…In vivo ectopic bone formation was assayed as previously described [23]. Briefly, on reaching their first confluence, 1 Â 10 6 of CFU-f and NAMP progeny cells were resuspended in 30 ll of fibrinogen (20 mg/ml; Baxter, Austria, www.baxter.at), quickly mixed with 30 ll of thrombin (6 IU/ml; Baxter), and loaded onto 35 lg of bovine bone-derived granules (Bio-Oss, Geistlich, Switzerland, www.geistlich.com).…”

Section: Assessment Of Bone Formation In Vivomentioning

confidence: 99%

Fibroblast Growth Factor-2 Maintains a Niche-Dependent Population of Self-Renewing Highly Potent Non-adherent Mesenchymal Progenitors Through FGFR2c

et al. 2012

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Bone marrow (BM) mesenchymal stem/stromal cells (MSC) are a heterogeneous population of multipotent progenitors currently under investigation for a variety of applications in regenerative medicine. While self-renewal of stem cells in different tissues has been demonstrated to be regulated by specialized microenvironments called niches, it is still unclear whether a self-renewing niche also exists for MSC. Here, we show that primary human BM cultures contain a population of intrinsically non-adherent mesenchymal progenitors (NAMP) with features of more primitive progenitors than the initially adhering colonyforming units-fibroblast (CFU-f). In fact, NAMP could generate an adherent progeny: (a) enriched with early mesenchymal populations (CD1461, SSEA-11, and SSEA-41); (b) with significantly greater proliferation and multilineage differentiation potential in vitro; and (c) capable of threefold greater bone formation in vivo than the corresponding CFU-f. Upon serial replating, NAMP were able to regenerate and expand in suspension as non-adherent clonogenic progenitors, while also giving rise to an adherent progeny. This took place at the cost of a gradual loss of proliferative potential, shown by a reduction in colony size, which could be completely prevented when NAMP were expanded on the initially adhering BM fraction. Mechanistically, we found that NAMP crucially depend on fibroblast growth factor (FGF)-2 signaling through FGFR2c for their survival and expansion. Furthermore, NAMP maintenance depends at least in part on humoral signals distinct from FGF-2. In conclusion, our data show a niche/progenitor organization in vitro, in which the BM adherent fraction provides a self-renewing microenvironment for primitive NAMP.

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Section: Assessment Of Bone Formation In Vivomentioning

confidence: 99%

Fibroblast Growth Factor-2 Maintains a Niche-Dependent Population of Self-Renewing Highly Potent Non-adherent Mesenchymal Progenitors Through FGFR2c

et al. 2012

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“…Moreover, by streamlining culture processes and bypassing operator/handlingdependent procedures, bioreactor-based systems have the potential to increase the robustness and stability of the graft manufacturing process [16,17].…”

Section: Scientific Aspectsmentioning

confidence: 99%

Bioreactor-based roadmap for the translation of tissue engineering strategies into clinical products

Martin

Smith

Wendt

2009

Trends in Biotechnology

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“…Researchers utilize a variety of scaffolds to study the behavior of MSCs in 3D cultures. [29][30][31][32][33][34] Typically, these 3D scaffolds are composed of foreign materials (either natural or synthetic) and often elicit an atypical cellular response. Therefore, to study the behavior of MSCs in vitro, an ideal 3D environment should be composed of materials that mimic the native tissue.…”

Section: Introductionmentioning

confidence: 99%

Stromal-Cell-Derived Extracellular Matrix Promotes the Proliferation and Retains the Osteogenic Differentiation Capacity of Mesenchymal Stem Cells on Three-Dimensional Scaffolds

Antebi

Zhang

Wang

et al. 2015

Tissue Engineering Part C: Methods

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To date, expansion of bone-marrow-derived mesenchymal stem cells (MSCs) is typically carried out on twodimensional (2D) tissue culture plastic. Since this 2D substratum is very different from the physiological situation, MSCs gradually lose their unique multipotent properties during expansion. Recently, the role of the extracellular matrix (ECM) microenvironment (''niche'') in facilitating and regulating stem cell behavior in vivo has been elucidated. As a result, investigators have shifted their efforts toward developing threedimensional (3D) scaffolds capable of functioning like the native tissue ECM. In this study, we demonstrated that stromal-cell-derived ECM, formed within a collagen/hydroxyapatite (Col/HA) scaffold to mimic the bone marrow ''niche,'' promoted MSC proliferation and preserved their differentiation capacity. The ECM was synthesized by MSCs to reconstitute the tissue-specific 3D microenvironment in vitro. Following deposition of the ECM inside Col/HA scaffold, the construct was decellularized and reseeded with MSCs to study their behavior. The data showed that MSCs cultured on the ECM-Col/HA scaffolds grew significantly faster than the cells from the same batch cultured on the regular Col/HA scaffolds. In addition, MSCs cultured on the ECMCol/HA scaffolds retained their ''stemness'' and osteogenic differentiation capacity better than MSCs cultured on regular Col/HA scaffolds. When ECM-Col/HA scaffolds were implanted into immunocompromised mice, with or without loading MSCs, it was found that those scaffolds formed less bone as compared with regular Col/ HA scaffolds (i.e., without ECM), in both cases of with or without loading MSCs. The in vivo study further confirmed that the ECM-Col/HA scaffold was a suitable mimic of the bone marrow ''niche.'' This novel 3D stromal-cell-derived ECM system has the potential to be developed into a biomedical platform for regenerative medicine applications.

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Three‐Dimensional Perfusion Culture of Human Bone Marrow Cells and Generation of Osteoinductive Grafts

Cited by 188 publications

References 34 publications

Fibroblast Growth Factor-2 Maintains a Niche-Dependent Population of Self-Renewing Highly Potent Non-adherent Mesenchymal Progenitors Through FGFR2c

Fibroblast Growth Factor-2 Maintains a Niche-Dependent Population of Self-Renewing Highly Potent Non-adherent Mesenchymal Progenitors Through FGFR2c

Bioreactor-based roadmap for the translation of tissue engineering strategies into clinical products

Stromal-Cell-Derived Extracellular Matrix Promotes the Proliferation and Retains the Osteogenic Differentiation Capacity of Mesenchymal Stem Cells on Three-Dimensional Scaffolds

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