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Spheroid Culture of Mesenchymal Stem Cells.

Cesarz Z, Tamama K - Stem Cells Int (2015)

Bottom Line: Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids.Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses.In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

ABSTRACT
Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti-inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.

No MeSH data available.


Related in: MedlinePlus

Clinical significance of MSC spheroids. Formation of spheroidal aggregates (1) enhances paracrine secretion of angiogenic, antitumorigenic, and pro- and anti-inflammatory factors, (2) improves cell survival, (3) increases differentiation potentials, and (4) delays replicative senescence of MSCs (ANG: angiogenin; ANGPT2: angiopoietin 2; CCL2: chemokine (C-C motif) ligand 2; CCL7: chemokine (C-C motif) ligand 7; FGF2: fibroblast growth factor 2; HGF: hepatocyte growth factor; IL1A: interleukin 1α; IL1B: interleukin 1β; IL8: interleukin 8; IL24: interleukin 24; PGE2: prostaglandin E2; TNFAIP6 (TSG6): tumor necrosis factor α-induced protein 6 (tumor necrosis factor α stimulated gene/protein 6); VEGFA: vascular endothelial growth factor-A).
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Related In: Results  -  Collection


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fig1: Clinical significance of MSC spheroids. Formation of spheroidal aggregates (1) enhances paracrine secretion of angiogenic, antitumorigenic, and pro- and anti-inflammatory factors, (2) improves cell survival, (3) increases differentiation potentials, and (4) delays replicative senescence of MSCs (ANG: angiogenin; ANGPT2: angiopoietin 2; CCL2: chemokine (C-C motif) ligand 2; CCL7: chemokine (C-C motif) ligand 7; FGF2: fibroblast growth factor 2; HGF: hepatocyte growth factor; IL1A: interleukin 1α; IL1B: interleukin 1β; IL8: interleukin 8; IL24: interleukin 24; PGE2: prostaglandin E2; TNFAIP6 (TSG6): tumor necrosis factor α-induced protein 6 (tumor necrosis factor α stimulated gene/protein 6); VEGFA: vascular endothelial growth factor-A).

Mentions: MSC-based therapeutics is a promising approach in the field of autoimmune diseases, regenerative medicine, and tissue engineering. However, the beneficial effects of MSC-based therapeutics in initial small scale clinical studies are often not substantiated by large randomized-controlled clinical trials, strongly indicating the urgent need of further optimization of cell-based therapy [71–73]. There are various approaches to improve the efficacy of MSC-based therapeutics, and MSC preparation as spheroids represents one method of optimization. Spheroid formation has been shown to enhance anti-inflammatory effects, augment tissue regenerative and reparative effects with enhanced angiogenesis, facilitate differentiation potentials of multiple lineages, increase posttransplant survival of MSCs, improve MSC stemness, and delay in vitro replicative senescent processes, as discussed in detail below (Figure 1).


Spheroid Culture of Mesenchymal Stem Cells.

Cesarz Z, Tamama K - Stem Cells Int (2015)

Clinical significance of MSC spheroids. Formation of spheroidal aggregates (1) enhances paracrine secretion of angiogenic, antitumorigenic, and pro- and anti-inflammatory factors, (2) improves cell survival, (3) increases differentiation potentials, and (4) delays replicative senescence of MSCs (ANG: angiogenin; ANGPT2: angiopoietin 2; CCL2: chemokine (C-C motif) ligand 2; CCL7: chemokine (C-C motif) ligand 7; FGF2: fibroblast growth factor 2; HGF: hepatocyte growth factor; IL1A: interleukin 1α; IL1B: interleukin 1β; IL8: interleukin 8; IL24: interleukin 24; PGE2: prostaglandin E2; TNFAIP6 (TSG6): tumor necrosis factor α-induced protein 6 (tumor necrosis factor α stimulated gene/protein 6); VEGFA: vascular endothelial growth factor-A).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663368&req=5

fig1: Clinical significance of MSC spheroids. Formation of spheroidal aggregates (1) enhances paracrine secretion of angiogenic, antitumorigenic, and pro- and anti-inflammatory factors, (2) improves cell survival, (3) increases differentiation potentials, and (4) delays replicative senescence of MSCs (ANG: angiogenin; ANGPT2: angiopoietin 2; CCL2: chemokine (C-C motif) ligand 2; CCL7: chemokine (C-C motif) ligand 7; FGF2: fibroblast growth factor 2; HGF: hepatocyte growth factor; IL1A: interleukin 1α; IL1B: interleukin 1β; IL8: interleukin 8; IL24: interleukin 24; PGE2: prostaglandin E2; TNFAIP6 (TSG6): tumor necrosis factor α-induced protein 6 (tumor necrosis factor α stimulated gene/protein 6); VEGFA: vascular endothelial growth factor-A).
Mentions: MSC-based therapeutics is a promising approach in the field of autoimmune diseases, regenerative medicine, and tissue engineering. However, the beneficial effects of MSC-based therapeutics in initial small scale clinical studies are often not substantiated by large randomized-controlled clinical trials, strongly indicating the urgent need of further optimization of cell-based therapy [71–73]. There are various approaches to improve the efficacy of MSC-based therapeutics, and MSC preparation as spheroids represents one method of optimization. Spheroid formation has been shown to enhance anti-inflammatory effects, augment tissue regenerative and reparative effects with enhanced angiogenesis, facilitate differentiation potentials of multiple lineages, increase posttransplant survival of MSCs, improve MSC stemness, and delay in vitro replicative senescent processes, as discussed in detail below (Figure 1).

Bottom Line: Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids.Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses.In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

ABSTRACT
Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti-inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.

No MeSH data available.


Related in: MedlinePlus