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3. Biomimetic cell-laden meha hydrogels for the regeneration of cartilage tissue

Author

Tsanaktsidou, Evgenia, Kammona, Olga, Labude, Norina, Neuss, Sabine, Krüger, Melanie, Kock, Linda, Kiparissides, Costas, Tsanaktsidou, Evgenia, Kammona, Olga, Labude, Norina, Neuss, Sabine, Krüger, Melanie, Kock, Linda, and Kiparissides, Costas

Abstract

Methacrylated hyaluronic acid (MeHA) and chondroitin sulfate (CS)-biofunctionalized MeHA(CS-MeHA), were crosslinked in the presence of a matrix metalloproteinase 7 (MMP7)-sensitive peptide. The synthesized hydrogels were embedded with either human mesenchymal stem cells (hMSCs) or chondrocytes, at low concentrations, and subsequently cultured in a stem cell medium (SCM) or chondrogenic induction medium (CiM). The pivotal role of the synthesized hydrogels in promoting the expression of cartilage-related genes and the formation of neocartilage tissue despite the low concentration of encapsulated cells was assessed. It was found that hMSC-laden MeHA hydrogels cultured in an expansion medium exhibited a significant increase in the expression of chondrogenic markers compared to hMSCs cultured on a tissue culture polystyrene plate (TCPS). This favorable outcome was further enhanced for hMSC-laden CS-MeHA hydrogels, indicating the positive effect of the glycosaminoglycan binding peptide on the differentiation of hMSCs towards a chondrogenic phenotype. However, it was shown that an induction medium is necessary to achieve full span chondrogenesis. Finally, the histological analysis of chondrocyte-laden MeHA hydrogels cultured on an ex vivo osteochondral platform revealed the deposition of glycosaminoglycans (GAGs) and the arrangement of chondrocyte clusters in isogenous groups, which is characteristic of hyaline cartilage morphology.

Published
2020

8. Cord blood-hematopoietic stem cell expansion in 3D fibrin scaffolds with stromal support.

Author

Ferreira MS, Jahnen-Dechent W, Labude N, Bovi M, Hieronymus T, Zenke M, Schneider RK, and Neuss S

Subjects
Animals, Antigens, CD34 biosynthesis, Biocompatible Materials, Bone Marrow Cells cytology, Cell Proliferation, Cell Transplantation methods, Cells, Cultured cytology, Cytokines metabolism, Humans, Mice, Mice, Inbred NOD, Mice, SCID, Microscopy, Electron, Scanning methods, Phenotype, Tissue Engineering methods, Umbilical Cord cytology, Fetal Blood cytology, Fibrin chemistry, Hematopoietic Stem Cells cytology, Tissue Scaffolds chemistry
Abstract

Expansion of multipotent, undifferentiated and proliferating cord blood (CB)-hematopoietic stem cells (HSC) in vitro is limited and insufficient. Bone marrow (BM) engineering in vitro allows mimicking the main components of the hematopoietic niche compared to conventional expansion strategies. In this study, four different 3D biomaterial scaffolds (PCL, PLGA, fibrin and collagen) were tested for freshly isolated cord blood (CB)-CD34(+) cell expansion in presence of (i) efficient exogenous cytokine supplementation and (ii) umbilical cord (UC)-mesenchymal stem cells (MSC). Cell morphology, growth and proliferation were analyzed in vitro as well as multi-organ engraftment and multilineage differentiation in a murine transplantation model. All scaffolds, except 3D PLGA meshes, supported CB-CD34(+) cell expansion, which was additionally stimulated by UC-MSC support. CB-CD34(+) cells cultured on human-derived 3D fibrin scaffolds with UC-MSC support i) reached the highest overall growth (5 × 10(8)-fold expansion of total nuclear cells after fourteen days and 3 × 10(7)-fold expansion of CD34(+) cells after seven days, p < 0.001), ii) maintained a more primitive immunophenotype for more cell divisions, iii) exhibited superior morphological, migratory and adhesive properties, and iv) showed the significantly highest numbers of engraftment and multilineage differentiation (CD45, CD34, CD13, CD3 and CD19) in BM, spleen and peripheral blood in long-term transplanted NSG mice compared to the other 3D biomaterial scaffolds. Thus, the 3D fibrin scaffold based BM-mimicry strategy reveals optimal requirements for translation into clinical protocols for CB expansion and transplantation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2012
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