Dataset Information

Mesenchymal stem cell delivery routes and fate.

ABSTRACT: MSC have been used in diverse animal disease models to investigate their regenerative capacity. Although the clinical outcome was often encouraging, the mode of action of the cells remains unresolved. Differentiation of MSC into cell types of their target organs was only rarely shown, with the exception of the musculoskeletal system. Thus, the effect of the cells on the clinical outcome in several disease models of tissue degeneration must be independent of trans-differentiation and caused by indirect or paracrine effects. Furthermore, tracking of the cells in vivo revealed that only a small proportion of the cells home and persists in the target sites, and that most of the cells are not detectable after 7?14 days post transplantation. It seems that MSC can deliver a profound clinical effect without trans-differentiation, without homing to target organs in significant numbers and despite the cell's disappearance within short periods of time. These finding also suggest that the full potency of MSC has not yet been exploited in the current applications. Here we will provide an overview of the different routes used for cell delivery and the fate of the cells after transplantation. The effects on clinical outcome are discussed with respect to the role cell entrapment in non-target organs may play for the observed clinical effects.

SUBMITTER: Kurtz A

PROVIDER: S-EPMC4021770 | biostudies-other | 2008 Nov

REPOSITORIES: biostudies-other

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Mesenchymal stem cell delivery routes and fate.

Kurtz Andreas A

International journal of stem cells 20081101 1

MSC have been used in diverse animal disease models to investigate their regenerative capacity. Although the clinical outcome was often encouraging, the mode of action of the cells remains unresolved. Differentiation of MSC into cell types of their target organs was only rarely shown, with the exception of the musculoskeletal system. Thus, the effect of the cells on the clinical outcome in several disease models of tissue degeneration must be independent of trans-differentiation and caused by in ...[more]

PMID: 24855503

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Project description:Background:Hydrogels with tuneable mechanical properties are an attractive material platform for 3D bioprinting. Thus far, numerous studies have confirmed that the biophysical cues of hydrogels, such as stiffness, are known to have a profound impact on mesenchymal stem cell (MSC) differentiation; however, their differentiation potential within 3D-bioprinted hydrogels is not completely understood. Here, we propose a protocol for the exploration of how the stiffness of alginate-gelatin (Alg-Gel) composite hydrogels (the widely used bioink) affects the differentiation of MSCs in the presence or absence of differentiation inducing factors. Methods:Two types of Alg-Gel composite hydrogels (Young's modulus: 50 kPa vs. 225 kPa) were bioprinted independently of porosity. Then, stiffness-induced biases towards adipogenic and osteogenic differentiation of the embedded MSCs were analysed by co-staining with alkaline phosphatase (ALP) and oil red O. The expression of specific markers at the gene level was detected after a 3-day culture. Results:Confocal microscopy indicated that all tested hydrogels supported MSC growth and viability during the culture period. Higher expression of adipogenic and osteogenic markers (ALP and lipoprotein lipase (LPL)) in stiffer 3D-bioprinted matrices demonstrated a more significant response of MSCs to stiffer hydrogels with respect to differentiation, which was more robust in differentiation-inducing medium. However, the LPL expression in stiffer 3D-bioprinted constructs was reduced at day 3 regardless of the presence of differentiation-inducing factors. Although MSCs embedded in softer hydrogels to some extent proceeded toward adipogenic and osteogenic lineages within a few days, their differentiation seemed to be slower and more limited. Interestingly, the hydrogel itself (without differentiation-inducing factors) exhibited a slight effect on whether MSCs differentiated towards an adipogenic or an osteogenic fate. Considering that the mechano-regulated protein Yes-associated protein (YAP) is involved in MSC fate decisions, we further found that inhibition of YAP significantly downregulated the expression of ALP and LPL in MSCs in stiffer constructs regardless of the induced growth factors present. Conclusions:These results demonstrate that the differentiation of MSCs in 3D-bioprinted matrices is dependent on hydrogel stiffness, which emphasizes the importance of biophysical cues as a determinant of cellular behaviour.

Dataset Information

Mesenchymal stem cell delivery routes and fate.

Publications

Mesenchymal stem cell delivery routes and fate.

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