Injectable extracellular matrix hydrogels contribute to native cell infiltration in a rat partial nephrectomy model

Kushige, Hiroko; Amano, Yuki; Yagi, Hiroshi; Morisaku, Toshinori; Kojima, Hideaki; Satou, Akiko; Hamada, Kenichi; Kitagawa, Yuko

doi:10.1002/jbm.b.35144

Cited by 5 publications

(6 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we showed that the proliferative activity was higher in 4 mg/ml gels than in gels of higher concentrations. We previously reported that different ECM concentrations change the elasticity of the scaffold and the pore size of the fiber structure 28 , and these mechanical properties may also serve as external signals to influence cell infiltration and/or metabolism 58 . However, given the multi-component nature of decellularized hydrogels, these mechanical factors are so complex and interdependent that concluding how individual properties may affect the behavior of MSCs was difficult in this study.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Combinational Treatment Involving Decellularized Extracellular Matrix Hydrogels With Mesenchymal Stem Cells Increased the Efficacy of Cell Therapy in Pancreatitis

et al. 2023

Self Cite

View full text Add to dashboard Cite

Cell transplantation using mesenchymal stem cells (MSCs) has emerged as a promising approach to repairing and regenerating injured or impaired organs. However, the survival and retention of MSCs following transplantation remain a challenge. Therefore, we investigated the efficacy of co-transplantation of MSCs and decellularized extracellular matrix (dECM) hydrogels, which have high cytocompatibility and biocompatibility. The dECM solution was prepared by enzymatic digestion of an acellular porcine liver scaffold. It could be gelled and formed into porous fibrillar microstructures at physiological temperatures. MSCs expanded three-dimensionally in the hydrogel without cell death. Compared to the 2-dimensional cell culture, MSCs cultured in the hydrogel showed increased secretion of hepatocyte growth factor (HGF) and tumor necrosis factor-inducible gene 6 protein (TSG-6), both of which are major anti-inflammatory and anti-fibrotic paracrine factors of MSCs, under TNFα stimulation. In vivo experiments showed that the co-transplantation of MSCs with dECM hydrogel improved the survival rate of engrafted cells compared to those administered without the hydrogel. MSCs also demonstrated therapeutic effects in improving inflammation and fibrosis of pancreatic tissue in a dibutyltin dichloride (DBTC)-induced rat pancreatitis model. Combinational use of dECM hydrogel with MSCs is a new strategy to overcome the challenges of cell therapy using MSCs and can be used for treating chronic inflammatory diseases in clinical settings.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The fixed samples were then embedded in paraffin and subsequently sectioned to 0.5 µm thickness. Sections were subjected to hematoxylin and eosin (H&E) and AZAN staining as previously described 28 . In an immunohistological analysis, the sections were deparaffinized and rehydrated, and the antigens were retrieved.…”

Section: Methodsmentioning

confidence: 99%

Combinational Treatment Involving Decellularized Extracellular Matrix Hydrogels With Mesenchymal Stem Cells Increased the Efficacy of Cell Therapy in Pancreatitis

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The L-ECM was prepared according to a previous report, with some modi cations [24] [50]. Brie y, livers were removed from the disinfected peritoneal cavity of pigs, frozen at − 80°C, and thawed at 4°C for over 24 h for the freeze-thaw process, a common initial decellularization step.…”

Section: Decellularization Of Porcine Livermentioning

confidence: 99%

“…Kidney-derived decellularized ECM hydrogels have also been reported to enhance vascularization. [23] [24] In this study, we hypothesized that a decellularized liver hydrogel contributes to the survival of transplanted hepatocytes and the expression of their inherent functions via enhanced self-organization and vascularization. Here, we developed a liver-derived extracellular matrix (L-ECM) gel that functions as a scaffold material and investigated the orthotopic transplantation of mature hepatocytes in a brotic liver model.…”

Section: Introductionmentioning

confidence: 99%

Decellularized liver hydrogel enhances cell engraftment in orthotopic hepatocyte transplantation by promoting cell–cell interaction and angiogenesis

Udagawa

Nagata

Yagi

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet to overcome poor cell engraftment and function. Therefore, we developed an orthotopic hepatocyte transplantation method using a liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into the hydrogel solution in vitro, and the gel solution was immediately gelated in 37 ℃ incubators to investigate the affinity between mature human hepatocyte and the L-ECM-gel. During the 3-day cultivation in hepatocyte medium, PXB cells formed cell aggregates via cell–cell interactions. Quantitative analysis revealed human albumin production in culture supernatants. For the in vivo assay, PXB cells were encapsulated in the L-ECM gel and transplanted between the liver lobes of normal rats. Pathologically, the L-ECM gel was localized at the transplant site and retained PXB cells. Cell survival and hepatic function marker expression were verified in another rat model wherein thioacetamide was administered to induce liver fibrosis. Moreover, cell–cell interactions and angiogenesis were enhanced in the L-ECM gel compared to that in the collagen gel. Our results indicate that L-ECM gels can help engraft transplanted hepatocytes and express hepatic function as a scaffold for cell transplantation.

show abstract

“…Angiogenesis is another important factor in hepatocyte engraftment 24 , and is related to the long-term engraftment of transplanted hepatocytes 25 . Kidney-derived decellularized ECM hydrogels have also been reported to enhance vascularization 26 , 27 .…”

Section: Introductionmentioning

confidence: 99%

A Novel Approach to Orthotopic Hepatocyte Transplantation Engineered With Liver Hydrogel for Fibrotic Livers, Enhancing Cell–Cell Interaction and Angiogenesis

Udagawa,

Nagata,

Yagi

et al. 2024

Cell Transplant

View full text Add to dashboard Cite

Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet to overcome poor cell engraftment and function. Therefore, we developed an orthotopic HCT method using a liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into the hydrogel solution in vitro, and the gel solution was immediately gelated in 37°C incubators to investigate the affinity between mature human hepatocyte and the L-ECM gel. During the 3-day cultivation in hepatocyte medium, PXB cells formed cell aggregates via cell–cell interactions. Quantitative analysis revealed human albumin production in culture supernatants. For the in vivo assay, PXB cells were encapsulated in the L-ECM gel and transplanted between the liver lobes of normal rats. Pathologically, the L-ECM gel was localized at the transplant site and retained PXB cells. Cell survival and hepatic function marker expression were verified in another rat model wherein thioacetamide was administered to induce liver fibrosis. Moreover, cell–cell interactions and angiogenesis were enhanced in the L-ECM gel compared with that in the collagen gel. Our results indicate that L-ECM gels can help engraft transplanted hepatocytes and express hepatic function as a scaffold for cell transplantation.

show abstract

Injectable extracellular matrix hydrogels contribute to native cell infiltration in a rat partial nephrectomy model

Cited by 5 publications

References 39 publications

Combinational Treatment Involving Decellularized Extracellular Matrix Hydrogels With Mesenchymal Stem Cells Increased the Efficacy of Cell Therapy in Pancreatitis

Combinational Treatment Involving Decellularized Extracellular Matrix Hydrogels With Mesenchymal Stem Cells Increased the Efficacy of Cell Therapy in Pancreatitis

Decellularized liver hydrogel enhances cell engraftment in orthotopic hepatocyte transplantation by promoting cell–cell interaction and angiogenesis

A Novel Approach to Orthotopic Hepatocyte Transplantation Engineered With Liver Hydrogel for Fibrotic Livers, Enhancing Cell–Cell Interaction and Angiogenesis

Contact Info

Product

Resources

About