scholarly journals Comparison of the Translational Potential of Human Mesenchymal Progenitor Cells from Different Bone Entities for Autologous 3D Bioprinted Bone Grafts

2021 ◽  
Vol 22 (2) ◽  
pp. 796
Author(s):  
Anna-Klara Amler ◽  
Patrick H. Dinkelborg ◽  
Domenic Schlauch ◽  
Jacob Spinnen ◽  
Stefan Stich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Minimally Invasive ◽  
Progenitor Cells ◽  
Alveolar Bone ◽  
Bone Grafts ◽  
Osteogenic Potential ◽  
3D Bioprinting ◽  
Mesenchymal Progenitor Cells ◽  
Cell Source ◽  
Autologous Bone

Reconstruction of segmental bone defects by autologous bone grafting is still the standard of care but presents challenges including anatomical availability and potential donor site morbidity. The process of 3D bioprinting, the application of 3D printing for direct fabrication of living tissue, opens new possibilities for highly personalized tissue implants, making it an appealing alternative to autologous bone grafts. One of the most crucial hurdles for the clinical application of 3D bioprinting is the choice of a suitable cell source, which should be minimally invasive, with high osteogenic potential, with fast, easy expansion. In this study, mesenchymal progenitor cells were isolated from clinically relevant human bone biopsy sites (explant cultures from alveolar bone, iliac crest and fibula; bone marrow aspirates; and periosteal bone shaving from the mastoid) and 3D bioprinted using projection-based stereolithography. Printed constructs were cultivated for 28 days and analyzed regarding their osteogenic potential by assessing viability, mineralization, and gene expression. While viability levels of all cell sources were comparable over the course of the cultivation, cells obtained by periosteal bone shaving showed higher mineralization of the print matrix, with gene expression data suggesting advanced osteogenic differentiation. These results indicate that periosteum-derived cells represent a highly promising cell source for translational bioprinting of bone tissue given their superior osteogenic potential as well as their minimally invasive obtainability.

scholarly journals Tenogenic Properties of Mesenchymal Progenitor Cells Are Compromised in an Inflammatory Environment

2018 ◽  
Vol 19 (9) ◽  
pp. 2549 ◽  
Author(s):  
Luisa Brandt ◽  
Susanna Schubert ◽  
Patrick Scheibe ◽  
Walter Brehm ◽  
Jan Franzen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Culture Conditions ◽  
Mesenchymal Progenitor Cells ◽  
Blood Leukocytes ◽  
Inflammatory Conditions ◽  
Tenogenic Differentiation ◽  
Adipose Derived Stromal Cells ◽  
Factor Α ◽  
The Impact

Transplantation of multipotent mesenchymal progenitor cells is a valuable option for treating tendon disease. Tenogenic differentiation leading to cell replacement and subsequent matrix modulation may contribute to the regenerative effects of these cells, but it is unclear whether this occurs in the inflammatory environment of acute tendon disease. Equine adipose-derived stromal cells (ASC) were cultured as monolayers or on decellularized tendon scaffolds in static or dynamic conditions, the latter represented by cyclic stretching. The impact of different inflammatory conditions, as represented by supplementation with interleukin-1β and/or tumor necrosis factor-α or by co-culture with allogeneic peripheral blood leukocytes, on ASC functional properties was investigated. High cytokine concentrations increased ASC proliferation and osteogenic differentiation, but decreased chondrogenic differentiation and ASC viability in scaffold culture, as well as tendon scaffold repopulation, and strongly influenced musculoskeletal gene expression. Effects regarding the latter differed between the monolayer and scaffold cultures. Leukocytes rather decreased ASC proliferation, but had similar effects on viability and musculoskeletal gene expression. This included decreased expression of the tenogenic transcription factor scleraxis by an inflammatory environment throughout culture conditions. The data demonstrate that ASC tenogenic properties are compromised in an inflammatory environment, with relevance to their possible mechanisms of action in acute tendon disease.

scholarly journals Inducible Expression of Chimeric EWS/ETS Proteins Confers Ewing's Family Tumor-Like Phenotypes to Human Mesenchymal Progenitor Cells

2008 ◽  
Vol 28 (7) ◽  
pp. 2125-2137 ◽  
Author(s):  
Yoshitaka Miyagawa ◽  
Hajime Okita ◽  
Hideki Nakaijima ◽  
Yasuomi Horiuchi ◽  
Ban Sato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Ectopic Expression ◽  
Chromosomal Translocations ◽  
Mesenchymal Progenitor Cells ◽  
Pediatric Tumor ◽  
Ets Proteins ◽  
Polygonal Cell ◽  
Transcription Factor Genes ◽  
Ets Transcription Factor

ABSTRACT Ewing's family tumor (EFT) is a rare pediatric tumor of unclear origin that occurs in bone and soft tissue. Specific chromosomal translocations found in EFT cause EWS to fuse to a subset of ets transcription factor genes (ETS), generating chimeric EWS/ETS proteins. These proteins are believed to play a crucial role in the onset and progression of EFT. However, the mechanisms responsible for the EWS/ETS-mediated onset remain unclear. Here we report the establishment of a tetracycline-controlled EWS/ETS-inducible system in human bone marrow-derived mesenchymal progenitor cells (MPCs). Ectopic expression of both EWS/FLI1 and EWS/ERG proteins resulted in a dramatic change of morphology, i.e., from a mesenchymal spindle shape to a small round-to-polygonal cell, one of the characteristics of EFT. EWS/ETS also induced immunophenotypic changes in MPCs, including the disappearance of the mesenchyme-positive markers CD10 and CD13 and the up-regulation of the EFT-positive markers CD54, CD99, CD117, and CD271. Furthermore, a prominent shift from the gene expression profile of MPCs to that of EFT was observed in the presence of EWS/ETS. Together with the observation that EWS/ETS enhances the ability of cells to invade Matrigel, these results suggest that EWS/ETS proteins contribute to alterations of cellular features and confer an EFT-like phenotype to human MPCs.

Plasmid vectors harboring cellular promoters can induce prolonged gene expression in hematopoietic and mesenchymal progenitor cells

2005 ◽  
Vol 332 (2) ◽  
pp. 518-523 ◽  
Author(s):  
Hyang-Min Byun ◽  
Dongchul Suh ◽  
Youngsin Jeong ◽  
Hyung Seok Wee ◽  
Jung Mogg Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Mesenchymal Progenitor Cells ◽  
Plasmid Vectors

scholarly journals Rapid Production and Genetic Stability of Human Mesenchymal Progenitor Cells Derived from Human Somatic Cell Nuclear Transfer-Derived Pluripotent Stem Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9238
Author(s):  
Soo Kyung Jung ◽  
Jeoung Eun Lee ◽  
Chang Woo Lee ◽  
Sung Han Shim ◽  
Dong Ryul Lee
Keyword(s):  
Gene Expression ◽  
Somatic Cell ◽  
Progenitor Cells ◽  
Genetic Stability ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Mesenchymal Progenitor Cells ◽  
Direct Differentiation Method ◽  
Direct Differentiation ◽  
Differentiation Method

Pluripotent stem cell-derived mesenchymal progenitor cells (PSC-MPCs) are primarily derived through two main methods: three-dimensional (3D) embryoid body-platform (EB formation) and the 2D direct differentiation method. We recently established somatic cell nuclear transfer (SCNT)-PSC lines and showed their stemness. In the present study, we produced SCNT-PSC-MPCs using a novel direct differentiation method, and the characteristics, gene expression, and genetic stability of these MPCs were compared with those derived through EB formation. The recovery and purification of SCNT-PSC-Direct-MPCs were significantly accelerated compared to those of the SCNT-PSC-EB-MPCs, but both types of MPCs expressed typical surface markers and exhibited similar proliferation and differentiation potentials. Additionally, the analysis of gene expression patterns using microarrays showed very similar patterns. Moreover, array CGH analysis showed that both SCNT-PSC-Direct-MPCs and SCNT-PSC-EB-MPCs exhibited no significant differences in copy number variation (CNV) or single-nucleotide polymorphism (SNP) frequency. These results indicate that SCNT-PSC-Direct-MPCs exhibited high genetic stability even after rapid differentiation into MPCs, and the rate at which directly derived MPCs reached a sufficient number was higher than that of MPCs derived through the EB method. Therefore, we suggest that the direct method of differentiating MPCs from SCNT-PSCs can improve the efficacy of SCNT-PSCs applied to allogeneic transplantation.

scholarly journals Pharmacological targeting of KDM6A and KDM6B, as a novel therapeutic strategy for treating craniosynostosis in Saethre-Chotzen syndrome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Clara Pribadi ◽  
Esther Camp ◽  
Dimitrios Cakouros ◽  
Peter Anderson ◽  
Carlotta Glackin ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Progenitor Cells ◽  
Therapeutic Strategy ◽  
In Vivo Studies ◽  
Osteogenic Potential ◽  
Cranial Sutures ◽  
Mesenchymal Progenitor Cells ◽  
Suture Fusion ◽  
Twist 1

Abstract Background During development, excessive osteogenic differentiation of mesenchymal progenitor cells (MPC) within the cranial sutures can lead to premature suture fusion or craniosynostosis, leading to craniofacial and cognitive issues. Saethre-Chotzen syndrome (SCS) is a common form of craniosynostosis, caused by TWIST-1 gene mutations. Currently, the only treatment option for craniosynostosis involves multiple invasive cranial surgeries, which can lead to serious complications. Methods The present study utilized Twist-1 haploinsufficient (Twist-1del/+) mice as SCS mouse model to investigate the inhibition of Kdm6a and Kdm6b activity using the pharmacological inhibitor, GSK-J4, on calvarial cell osteogenic potential. Results This study showed that the histone methyltransferase EZH2, an osteogenesis inhibitor, is downregulated in calvarial cells derived from Twist-1del/+ mice, whereas the counter histone demethylases, Kdm6a and Kdm6b, known promoters of osteogenesis, were upregulated. In vitro studies confirmed that siRNA-mediated inhibition of Kdm6a and Kdm6b expression suppressed osteogenic differentiation of Twist-1del/+ calvarial cells. Moreover, pharmacological targeting of Kdm6a and Kdm6b activity, with the inhibitor, GSK-J4, caused a dose-dependent suppression of osteogenic differentiation by Twist-1del/+ calvarial cells in vitro and reduced mineralized bone formation in Twist-1del/+ calvarial explant cultures. Chromatin immunoprecipitation and Western blot analyses found that GSK-J4 treatment elevated the levels of the Kdm6a and Kdm6b epigenetic target, the repressive mark of tri-methylated lysine 27 on histone 3, on osteogenic genes leading to repression of Runx2 and Alkaline Phosphatase expression. Pre-clinical in vivo studies showed that local administration of GSK-J4 to the calvaria of Twist-1del/+ mice prevented premature suture fusion and kept the sutures open up to postnatal day 20. Conclusion The inhibition of Kdm6a and Kdm6b activity by GSK-J4 could be used as a potential non-invasive therapeutic strategy for preventing craniosynostosis in children with SCS. Graphical abstract Pharmacological targeting of Kdm6a/b activity can alleviate craniosynostosis in Saethre-Chotzen syndrome. Aberrant osteogenesis by Twist-1 mutant cranial suture mesenchymal progenitor cells occurs via deregulation of epigenetic modifiers Ezh2 and Kdm6a/Kdm6b. Suppression of Kdm6a- and Kdm6b-mediated osteogenesis with GSK-J4 inhibitor can prevent prefusion of cranial sutures.

scholarly journals Focus on periodontal engineering by 3D printing technology – A systematic review.

2020 ◽  
Vol 9 (6) ◽  
pp. 522-531
Author(s):  
Manchala Sesha Reddy ◽  
◽  
Shishir Ram Shetty ◽  
Raghavendra Manjunath Shetty ◽  
Venkataramana Vannala ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Periodontal Regeneration ◽  
Patient Treatment ◽  
Systematic Evaluation ◽  
Periodontal Ligament Cells ◽  
3D Bioprinting ◽  
Treatment Needs ◽  
Platelet Rich Fibrin

Three-dimensional (3D) bioprinting of cells is an emerging area of research but has not been explored yet in the context of periodontal tissue engineering. Objetive: This study reports on the optimization of the 3D bioprinting scaffolds and tissues used that could be applied clinically to seniors for the regenerative purpose to meet individual patient treatment needs. Material and Methods: We methodically explored the printability of various tissues (dentin pulp stem/progenitor cells, periodontal ligament stem/progenitor cells, alveolar bone stem/progenitor cells, advanced platelet-rich fibrin and injected platelet-rich fibrin) and scaffolds using 3D printers pertaining only to periodontal defects. The influence of different printing parameters with the help of scaffold to promote periodontal regeneration and to replace the lost structure has been evaluated. Results: This systematic evaluation enabled the selection of the most suited printing conditions for achieving high printing resolution, dimensional stability, and cell viability for 3D bioprinting of periodontal ligament cells. Conclusion: The optimized bioprinting system is the first step towards the reproducible manufacturing of cell laden, space maintaining scaffolds for the treatment of periodontal lesions.

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