3D spheroid culture system on micropatterned substrates for improved differentiation efficiency of multipotent mesenchymal stem cells

Wang, Wenjie; Itaka, Keiji; Ohba, Shinsuke; Nishiyama, Nobuhiro; Chung, Ung Il; Yamasaki, Yuichi; Kataoka, Kazunori

doi:10.1016/j.biomaterials.2009.01.030

Cited by 308 publications

(250 citation statements)

References 61 publications

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“…Recently there has been a series of publications on aggregation of MSCs either as a procedure for enhancing chrondrogenic differentiation of the cells (17)(18)(19) or to increase their therapeutic potential (20)(21)(22)(23). Because aggregated hMSCs were detected in the pulmonary microemboli observed after i.v.…”

mentioning

confidence: 99%

Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties

Bartosh¹,

Ylöstalo²,

Mohammadipoor³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

832

920

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Previous reports suggested that culture as 3D aggregates or as spheroids can increase the therapeutic potential of the adult stem/progenitor cells referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). Here we used a hanging drop protocol to prepare human MSCs (hMSCs) as spheroids that maximally expressed TNFα stimulated gene/protein 6 (TSG-6), the antiinflammatory protein that was expressed at high levels by hMSCs trapped in the lung after i.v. infusion and that largely explained the beneficial effects of hMSCs in mice with myocardial infarcts. The properties of spheroid hMSCs were found to depend critically on the culture conditions. Under optimal conditions for expression of TSG-6, the hMSCs also expressed high levels of stanniocalcin-1, a protein with both antiinflammatory and antiapoptotic properties. In addition, they expressed high levels of three anticancer proteins: IL-24, TNFα-related apoptosis inducing ligand, and CD82. The spheroid hMSCs were more effective than hMSCs from adherent monolayer cultures in suppressing inflammatory responses in a coculture system with LPS-activated macrophages and in a mouse model for peritonitis. In addition, the spheroid hMSCs were about one-fourth the volume of hMSCs from adherent cultures. Apparently as a result, larger numbers of the cells trafficked through the lung after i.v. infusion and were recovered in spleen, liver, kidney, and heart. The data suggest that spheroid hMSCs may be more effective than hMSCs from adherent cultures in therapies for diseases characterized by sterile tissue injury and unresolved inflammation and for some cancers that are sensitive to antiinflammatory agents.

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mentioning

confidence: 99%

Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties

Bartosh¹,

Ylöstalo²,

Mohammadipoor³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

832

920

View full text Add to dashboard Cite

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“…Bone differentiation potential of MSCs maintained in medium supplemented with rice bran extract Several studies have reported that three-dimensional spheroids of MSCs have enhanced biological functions, including the ability for osteogenic or adipogenic differentiation, or anti-inflammatory properties (Wang et al 2009;Miyagawa et al 2011;Bartosh et al 2010). Therefore, we hypothesized that the aggregation of rMSCs in STK1 with RBE would increase their potential for osteogenic differentiation.…”

Section: Treatment Of Mscs With Rice Bran Extract: Inducing Aggregatimentioning

confidence: 99%

“…Recent studies reported that MSCs readily aggregate and formed spheroids by culturing in particular substrates, such as micro-patterned substrates (Wang et al 2009), hydrophobic nano-pillars (Brammer et al 2011) and chitosan membranes (Hsu et al 2012), or by specialized methods, such as the hanging drop method (Bartosh et al 2010). Additionally, a recent study reported that N-cadherin is involved in the aggregation of MSCs (Hsu et al 2012), implying that RBE might induce aggregation of MSCs through expression of N-cadherin.…”

Section: Treatment Of Mscs With Rice Bran Extract: Inducing Aggregatimentioning

confidence: 99%

Rice bran extract affects differentiation of mesenchymal stem cells potency into osteogenic cells

et al. 2013

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As rice bran contains various nutrients and other proteins of which a part has biological effects on animal cells, we tested the effect of rice bran extract on rat mesenchymal stem cells (rMSCs) obtained from bone marrow. These rMSCs are pluripotent and can be readily induced to differentiate into a number of cell types, including bone and cartilage. rMSC was aggregated by culturing in serum-free condition with rice bran extract, but was not aggregated by culturing in serum-free condition or in serum-containing medium. Moreover, the longer aggregates of rMSCs were cultured in serum-free condition with rice bran extract, the more the aggregates grew. After two passages in serum-free conditions, rMSCs lost their potency for differentiation into osteogenic cells; however, the addition of rice bran extract to serumfree medium successfully prevented the loss of this ability for differentiation. In addition, MSC makers CD105 and CD166 gene expression in serum-free condition with rice barn extract corresponded to these expressions in serum-containing medium. This result suggests that certain factors in rice bran could be bioactive and contribute toward retaining the ability of MSCs to differentiate into osteogenic cells after passaging.

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“…During cell differentiation, both endogenous factors, such as cell-cell signal transmission, and exogenous factors, such as pharmacological application, play important roles. Micro and soft lithography-based surface modification of culture substrate enabled to control stem-cell-aggregation (EB; Embryoid body) sizes and therefore to increase cell differentiation efficiency through promotion of cell-cell signal interactions (Karp et al, 2007;Wang et al, 2009). Particularly, Park et al reported that small-size EBs of mouse ES cells (100 ~ 200 m of diameter) tended to differentiate into ectoderm and large-size EB (500 m of diameter) into mesoderm (Park et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Toward the Precise Control of Cell Differentiation Processes by Using Micro and Soft Lithography

Takayama¹,

Moriguchi²,

Kotani³

et al. 2011

Advances in Unconventional Lithography

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3D spheroid culture system on micropatterned substrates for improved differentiation efficiency of multipotent mesenchymal stem cells

Cited by 308 publications

References 61 publications

Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties

Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties

Rice bran extract affects differentiation of mesenchymal stem cells potency into osteogenic cells

Toward the Precise Control of Cell Differentiation Processes by Using Micro and Soft Lithography

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