Substrate-independent immunomodulatory characteristics of mesenchymal stem cells in three-dimensional culture

Li, Jing; Chen, Tong; Huang, Xiahe; Yun-feng, Zhao; Wang, Bin; Yin, Yanyun; Cui, Yi; Zhao, Yannan; Zhang, Ruiping; Wang, Xiu‐Jie; Wang, Yingchun; Dai, Jianwu

doi:10.1371/journal.pone.0206811

Cited by 25 publications

(22 citation statements)

References 37 publications

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“…Nonetheless, collagen, chitosan, and PLGA scaffolds enhanced the immunomodulatory potential of MSCs in a substrateindependent manner, despite discrepancies in gene expression. 49 However, pore size, stiffness, and surface chemistry may have a synergistic effect on MSCs. Indeed, four types of scaffolds with different biophysical and biochemical properties had different effects on the metabolic activity, distribution, and paracrine function of MSCs.…”

Section: Biochemistrymentioning

confidence: 99%

Harnessing the Properties of Biomaterial to Enhance the Immunomodulation of Mesenchymal Stem Cells

Yin

Shu

Qian

et al. 2019

Tissue Engineering Part B: Reviews

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Section: Biochemistrymentioning

confidence: 99%

Harnessing the Properties of Biomaterial to Enhance the Immunomodulation of Mesenchymal Stem Cells

Yin

Shu

Qian

et al. 2019

Tissue Engineering Part B: Reviews

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“…MSCs are reliant on low levels of stress signals in the stem cell niche and intact mitochondrial metabolism for sufficient ATP production to maintain stemness (Zhou et al, 2017). In addition to stemness, the immunomodulatory characteristics of 3D cultured MSCs was enhanced as defined by gene expression profile analysis at mRNA and protein level as compared to 2D cultured MSCs, but a link between immunomodulatory function of MSCs with SF formation, mitochondrial morphology and membrane elasticity was not described in detail (Li et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Influence of Platelet Lysate on 2D and 3D Amniotic Mesenchymal Stem Cell Cultures

Pasztorek

Roßmanith

Mayr

et al. 2019

Front. Bioeng. Biotechnol.

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The mechanobiological behavior of mesenchymal stem cells (MSCs) in two- (2D) or three-dimensional (3D) cultures relies on the formation of actin filaments which occur as stress fibers and depends on mitochondrial dynamics involving vimentin intermediate filaments. Here we investigate whether human platelet lysate (HPL), that can potentially replace fetal bovine serum for clinical-scale expansion of functional cells, can modulate the stress fiber formation, alter mitochondrial morphology, change membrane elasticity and modulate immune regulatory molecules IDO and GARP in amnion derived MSCs. We can provide evidence that culture supplementation with HPL led to a reduction of stress fiber formation in 2D cultured MSCs compared to a conventional growth medium (MSCGM). 3D MSC cultures, in contrast, showed decreased actin concentrations independent of HPL supplementation. When stress fibers were further segregated by their binding to focal adhesions, a reduction in ventral stress fibers was observed in response to HPL in 2D cultured MSCs, while the length of the individual ventral stress fibers increased. Dorsal stress fibers or transverse arcs were not affected. Interestingly, ventral stress fiber formation did not correlate with membrane elasticity. 2D cultured MSCs did not show differences in the Young's modulus when propagated in the presence of HPL and further cultivation to passage 3 also had no effect on membrane elasticity. In addition, HPL reduced the mitochondrial mass of 2D cultured MSCs while the mitochondrial mass in 3D cultured MSCs was low initially. When mitochondria were segregated into punctuate, rods and networks, a cultivation-induced increase in punctuate and network mitochondria was observed in 2D cultured MSCs of passage 3. Finally, mRNA and protein expression of the immunomodulatory molecule IDO relied on stimulation of 2D culture MSCs with pro-inflammatory cytokines IFN-γ and TNF-α with no effect upon HPL supplementation. GARP mRNA and surface expression was constitutively expressed and did not respond to HPL supplementation or stimulation with IFN-γ and TNF-α. In conclusion, we can say that MSCs cultivated in 2D and 3D are sensitive to medium supplementation with HPL with changes in actin filament formation, mitochondrial dynamics and membrane elasticity that can have an impact on the immunomodulatory function of MSCs.

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“…In this sense, in vitro HSC expansion systems should ideally mimic key microenvironmental characteristics of the bone marrow to achieve homeostasis and long-term maintenance of HSCs. Evidence suggests that signals existing in the tridimensional microenvironment of the cell are key to stemness maintenance and 3D culture systems are superior in maintaining pluripotency of several stem cells [ 53 , 54 , 55 ]. In addition to tridimensionality, chemical signals from other cellular elements of the niche and ECM components are also important and probably should be considered to establish maintenance and expansion ex vivo [ 3 , 4 , 26 , 27 , 56 , 57 ].…”

Section: Applications Of 3d Models Of Bm Niche For Cell Culturementioning

confidence: 99%

3D Scaffolds to Model the Hematopoietic Stem Cell Niche: Applications and Perspectives

Congrains¹,

Bianco²,

Rosa³

et al. 2021

Materials

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Hematopoietic stem cells (HSC) are responsible for the production of blood and immune cells during life. HSC fate decisions are dependent on signals from specialized microenvironments in the bone marrow, termed niches. The HSC niche is a tridimensional environment that comprises cellular, chemical, and physical elements. Introductorily, we will revise the current knowledge of some relevant elements of the niche. Despite the importance of the niche in HSC function, most experimental approaches to study human HSCs use bidimensional models. Probably, this contributes to the failure in translating many in vitro findings into a clinical setting. Recreating the complexity of the bone marrow microenvironment in vitro would provide a powerful tool to achieve in vitro production of HSCs for transplantation, develop more effective therapies for hematologic malignancies and provide deeper insight into the HSC niche. We previously demonstrated that an optimized decellularization method can preserve with striking detail the ECM architecture of the bone marrow niche and support HSC culture. We will discuss the potential of this decellularized scaffold as HSC niche model. Besides decellularized scaffolds, several other methods have been reported to mimic some characteristics of the HSC niche. In this review, we will examine these models and their applications, advantages, and limitations.

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Substrate-independent immunomodulatory characteristics of mesenchymal stem cells in three-dimensional culture

Cited by 25 publications

References 37 publications

Harnessing the Properties of Biomaterial to Enhance the Immunomodulation of Mesenchymal Stem Cells

Harnessing the Properties of Biomaterial to Enhance the Immunomodulation of Mesenchymal Stem Cells

Influence of Platelet Lysate on 2D and 3D Amniotic Mesenchymal Stem Cell Cultures

3D Scaffolds to Model the Hematopoietic Stem Cell Niche: Applications and Perspectives

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