Dataset Information

The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review.

ABSTRACT: The phenotypic change of macrophages (M?s) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and M?s remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and M?s during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and M?s. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163⁺ or CD206⁺ M2 M?s in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, M?s also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between M?s and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate M?s phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and M?s, have therapeutic potential in musculoskeletal diseases.

SUBMITTER: Xu H

PROVIDER: S-EPMC7726268 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review.

Xu Hongtao H Lee Chien-Wei CW Wang Yu-Fan YF Huang Shuting S Shin Lih-Ying LY Wang Yu-Hsuan YH Wan Zihao Z Zhu Xiaobo X Yung Patrick Shu Hang PSH Lee Oscar Kuang-Sheng OK

Frontiers in bioengineering and biotechnology 20201126

The phenotypic change of macrophages (Mφs) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based ...[more]

PMID: 33324622

Similar Datasets

Project description:Unlabelled: Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p < .05) enhanced chemotactic and proangiogenic properties and a significant (p < .05) decrease in the inflammatory mediator content. An analysis of the hMSC secretome revealed a specific profile under near anoxia: hMSCs increase their paracrine expression of the angiogenic mediators vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, RANTES, and monocyte chemoattractant protein 1 but significantly decrease expression of several inflammatory/immunomodulatory mediators. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine and could contribute to improving the efficacy of such therapies.SignificanceThe present study investigated and characterized select aspects of the human mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities.

Project description:The development of viable tissue surrogates requires a vascular network that sustains cell metabolism and tissue development. The coculture of endothelial cells (ECs) and mesenchymal stem cells (MSCs), the two key players involved in blood vessel formation, has been heralded in tissue engineering (TE) as one of the most promising approaches for scaffold vascularization. However, MSCs may exert both proangiogenic and antiangiogenic role. Furthermore, it is unclear which cell type is responsible for the upregulation of angiogenic pathways observed in EC:MSC cocultures. There is disagreement on the proangiogenic action of MSCs, as they have also been shown to negatively affect the formation of capillary networks. To address these issues, we investigated the regulation of key angiogenic pathways in scaffolds hosting different EC:MSC ratios fabricated through extrusion-based bioprinting. Human ECs were cocultured with either rat or human MSCs, and the regulation of fundamental angiogenic and arteriogenic pathways was analyzed through DNA, gene, and protein expression. The use of a hybrid human/rat coculture system facilitated pinpointing each cell type role in the regulation of specific genes and showed that MSCs exert a dose-dependent inhibitory effect on the EC expression of angiogenic factors within the first 24 h. Within a week of coculture, MSCs exert a proangiogenic effect, as corroborated in human/human bioprinted cocultures. Interestingly, juxtacrine signaling promoted secretion of the angiogenic factor vascular endothelial growth factor in direct cocultures (EC and MSC co-encapsulated), while paracrine signaling encouraged secretion of the arteriogenic factor platelet-derived growth factor in indirect cocultures (adjacent bioprinting of EC-laden and MSC-laden scaffolds). Overall, the use of a bioprinted system to elucidate EC:MSC interplay allows rapid leveraging of the data for novel vascular TE applications. Despite the transitory negative effect early in the culture, MSC presence is necessary for the regulation of pathways involved in arteriogenesis. With further validation in vivo, this study provides a possible explanation to the controversial findings present in literature and shows how MSC effect on angiogenic pathway regulation mimics the dynamics of blood vessel formation reported in literature and normally occurring in vivo. Impact Statement The coculturing of endothelial cells (ECs) and mesenchymal stem cells (MSCs) holds great promise in tissue engineering for the development of prevascularized tissue constructs. Yet, different studies report conflicting results on the role of MSCs, which can either support or inhibit vasculature formation. Furthermore, it is unclear how each cell type modulates distinct pathways involved in angiogenesis when cocultured. Using bioprinted hybrid coculture systems, we show that MSCs have both a time- and dose-dependent effect on the gene and protein expression of key angiogenic and arteriogenic factors by ECs. These findings, obtained in translationally relevant setup, can readily inform the design of vascularized scaffolds.

Dataset Information

The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review.

Publications

The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets