Scaffold-free 3D culturing enhance pluripotency, immunomodulatory factors, and differentiation potential of Wharton’s jelly-mesenchymal stem cells

Thakur, Gitika; Bok, Eun-Yeong; Kim, Saet-Byul; Jo, Chan‐Hee; Oh, Seong-Ju; Baek, Jong-Chul; Park, Ji‐Eun; Kang, Young‐Hoon; Lee, Sung‐Lim; Kumar, Raj; Rho, Gyu‐Jin

doi:10.1016/j.ejcb.2022.151245

Cited by 11 publications

(9 citation statements)

References 64 publications

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“…This enhancement occurs through various mechanisms, including facilitating essential cell-to-cell interactions and regulating crucial biological characteristics such as cell shape, oxygen levels, and nutrient intake. 106,107 Our in vitro results presented that the AD-MSCs/DPS induced the expression of M2 macrophage markers, which may shorten the time of polarization of macrophages from M1 to M2 phenotypic after DPS implantation in vivo. Therefore, we hypothesized that WJ-MSCs on the DPS and DPS after implantation could promote anti-inflammatory responses, regulate the immunomodulatory effects, and enhance bone regeneration.…”

Section: Discussionmentioning

confidence: 81%

Decellularized Placental Sponge: A Platform for Coculture of Mesenchymal Stem Cells/Macrophages to Assess an M2 Phenotype and Osteogenic Differentiation In Vitro and In Vivo

Khosrowpour,

Hashemi,

Mohammadi-Yeganeh

et al. 2024

ACS Omega

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Effective communication between immune and bone-forming cells is crucial for the successful healing of bone defects. This study aimed to assess the potential of a decellularized placental sponge (DPS) as a coculture system for inducing M1/M2 polarization in macrophages and promoting osteogenic differentiation in adipose-derived mesenchymal stem cells (AD-MSCs), both in vitro and in vivo. We prepared the DPS and conducted a comprehensive characterization of its biomechanical properties, antibacterial activity, and biocompatibility. In vitro, we examined the influence of the DPS on the polarization of macrophages cocultured with AD-MSCs through nitric oxide assays, cytokine assays, phagocytosis tests, and real-time polymerase chain reaction (PCR). For in vivo assessment, we utilized micro-CT imaging, histological evaluations, and real-time PCR to determine the impact of the DPS seeded with Wharton's jelly mesenchymal stem cells (WJ-MSCs) on bone regeneration in a calvarial bone defect model. The coculture of AD-MSCs and macrophages on the DPS led to increased production of IL-10, upregulation of CD206, Arg1, and YM1 gene expression, and enhanced phagocytic capacity for apoptotic thymocytes. Concurrently, it reduced the secretion of TNF-α and nitric oxide (NO), downregulated the expression of CD86, NOS2, and IRF5 genes, and decreased macrophage phagocytosis of yeast. These results indicated polarization of macrophages toward an M2-like phenotype. In vivo, the presence of the DPS resulted in enhanced bone formation at the defect site. Immunostaining demonstrated that both the DPS and DPS + WJ-MSC constructs induced macrophage polarization toward an M2 phenotype, as compared to the control defect. In conclusion, this immunomodulatory effect, coupled with its biocompatibility and biomechanical properties resembling natural bone, positions the DPS as an attractive candidate for further exploration in the field of bone tissue engineering and regenerative medicine.

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Section: Discussionmentioning

confidence: 81%

Decellularized Placental Sponge: A Platform for Coculture of Mesenchymal Stem Cells/Macrophages to Assess an M2 Phenotype and Osteogenic Differentiation In Vitro and In Vivo

Khosrowpour,

Hashemi,

Mohammadi-Yeganeh

et al. 2024

ACS Omega

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“…[ 34,35 ] Similarly, adipogenesis‐related adiponectin and CCAAT/enhancer‐binding protein α were reported to be activated after 3D culture and promoted adipogenic differentiation of MSCs. [ 36 ] Our present study further demonstrated that expanding the 3D culture to an industrial scale maintained this advantage in differentiation promotion.…”

Section: Discussionmentioning

confidence: 99%

A large‐scale production of mesenchymal stem cells and their exosomes for an efficient treatment against lung inflammation

Zhang,

Lin,

et al. 2024

Biotechnology Journal

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Mesenchymal stem cells (MSCs) and their produced exosomes have demonstrated inherent capabilities of inflammation‐guided targeting and inflammatory modulation, inspiring their potential applications as biologic agents for inflammatory treatments. However, the clinical applications of stem cell therapies are currently restricted by several challenges, and one of them is the mass production of stem cells to satisfy the therapeutic demands in the clinical bench. Herein, a production of human amnion‐derived MSCs (hMSCs) at a scale of over 1 × 109 cells per batch was reported using a three‐dimensional (3D) culture technology based on microcarriers coupled with a spinner bioreactor system. The present study revealed that this large‐scale production technology improved the inflammation‐guided migration and the inflammatory suppression of hMSCs, without altering their major properties as stem cells. Moreover, these large‐scale produced hMSCs showed an efficient treatment against the lipopolysaccharide (LPS)‐induced lung inflammation in mice models. Notably, exosomes collected from these large‐scale produced hMSCs were observed to inherit the efficient inflammatory suppression capability of hMSCs. The present study showed that 3D culture technology using microcarriers coupled with a spinner bioreactor system can be a promising strategy for the large‐scale expansion of hMSCs with improved anti‐inflammation capability, as well as their secreted exosomes.

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“…The use of culture systems containing human plasma and human embryo extracts maximizes the number of passages while maintaining the self-renewal and differentiation potential of iPSCs ( Wang et al, 2012 ). In addition, compared to 2D cultures, 3D culture systems can better mimic the microenvironment of SCs in vivo and enhance the stemness of different SC species ( Al Madhoun et al, 2016 ; Thakur et al, 2022 ). For example, a combination of 3D cell culture and natural brain tissue extracts can accelerate the differentiation of SCs into neuronal phenotypes ( Azizi et al, 2018 ).…”

Section: The Technical Route To Sc Therapymentioning

confidence: 99%

Enhancing regenerative medicine: the crucial role of stem cell therapy

Wang,

Deng,

Wang

et al. 2024

Front. Neurosci.

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Stem cells offer new therapeutic avenues for the repair and replacement of damaged tissues and organs owing to their self-renewal and multipotent differentiation capabilities. In this paper, we conduct a systematic review of the characteristics of various types of stem cells and offer insights into their potential applications in both cellular and cell-free therapies. In addition, we provide a comprehensive summary of the technical routes of stem cell therapy and discuss in detail current challenges, including safety issues and differentiation control. Although some issues remain, stem cell therapy demonstrates excellent potential in the field of regenerative medicine and provides novel tactics and methodologies for managing a wider spectrum of illnesses and traumas.

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Scaffold-free 3D culturing enhance pluripotency, immunomodulatory factors, and differentiation potential of Wharton’s jelly-mesenchymal stem cells

Cited by 11 publications

References 64 publications

Decellularized Placental Sponge: A Platform for Coculture of Mesenchymal Stem Cells/Macrophages to Assess an M2 Phenotype and Osteogenic Differentiation In Vitro and In Vivo

Decellularized Placental Sponge: A Platform for Coculture of Mesenchymal Stem Cells/Macrophages to Assess an M2 Phenotype and Osteogenic Differentiation In Vitro and In Vivo

A large‐scale production of mesenchymal stem cells and their exosomes for an efficient treatment against lung inflammation

Enhancing regenerative medicine: the crucial role of stem cell therapy

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