Cartilaginous and osteochondral tissue formation by human mesenchymal stem cells on three-dimensionally woven scaffolds
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ABSTRACT:
PROVIDER: PRJNA488091 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR7759644_1.fastq.gz | Fastqsanger.gz | |||
| SRR7759644_2.fastq.gz | Fastqsanger.gz | |||
| SRR7759645_1.fastq.gz | Fastqsanger.gz | |||
| SRR7759645_2.fastq.gz | Fastqsanger.gz | |||
| SRR7759646_1.fastq.gz | Fastqsanger.gz |
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Project description:The development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remain important challenges for regenerative medicine. The objective of this study was to assess of adult human mesenchymal stem cells (MSC) in large, three dimensionally woven poly(-caprolactone) (PCL) scaffolds in proximity to viable bone, both in a nude rat subcutaneous pouch model and under simulated conditions in vitro. In Study I, various scaffold permutations: PCL alone, PCL-bone, “point-of-care” seeded MSC-PCL-bone, and chondrogenically pre-cultured Ch-MSC-PCL-bone constructs were implanted in a dorsal, ectopic pouch in a nude rat. After eight weeks, cells in the PCL scaffold exhibited both chondrogenic and osteogenic gene expression profiles. Notably, while both tissue profiles were present, constructs that had been chondrogenically pre-cultured prior to implantation showed a loss of glycosaminoglycan (GAG) as well as the presence of mineralization along with the formation of trabeculae-like structures. In Study II of the study, the GAG loss and mineralization observed in Study I in vivo were recapitulated in vitro by the presence of either nearby bone or osteogenic culture medium additives but were prevented by a continued presence of chondrogenic medium additives. These data suggest conditions under which adult human stem cells in combination with polymer scaffolds synthesize functional and phenotypically distinct tissues based on the environmental conditions, and highlight the potential influence that paracrine factors from adjacent bone may have on MSC fate, once implanted in vivo for chondral or osteochondral repair.
2020-08-25 | GSE119095 | GEO
Project description:In this study, we aimed to develop microphysiological osteochondral (OC) tissue chips derived from human induced pluripotent stem cells (iPSCs) to model the pathologies of OA. We first induced iPSCs into mesenchymal progenitor cells (iMPCs) and optimized the chondro- and osteo-inductive conditions for iMPCs. Then iMPCs were encapsulated into photocrosslinked gelatin scaffolds and cultured within a dual-flow bioreactor, in which the top stream was chondrogenic medium and the bottom stream was osteogenic medium. After 28 days of differentiation, biphasic OC tissue and monophasic chondral (CH) tissue chips were successfully generated and phenotypes were confirmed by real time RT-PCR. The OC tissues were cut into Top and Bottom (Bot), and both parts were compared with each other. CH tissue were compared with their phenotype on Day 0. Total RNA was extracted from the samples and processed for qPCR according to the manufacturer's instructions.
2019-11-14 | GSE140332 | GEO
Project description:The development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remains an important challenge for regenerative medicine. The objective of this study was to assess adult human mesenchymal stem cells (MSCs) in large, three-dimensionally woven poly(?-caprolactone; PCL) scaffolds in proximity to viable bone, both in a nude rat subcutaneous pouch model and under simulated conditions in vitro. In Study I, various scaffold permutations-PCL alone, PCL-bone, "point-of-care" seeded MSC-PCL-bone, and chondrogenically precultured Ch-MSC-PCL-bone constructs-were implanted in a dorsal, ectopic pouch in a nude rat. After 8 weeks, only cells in the Ch-MSC-PCL constructs exhibited both chondrogenic and osteogenic gene expression profiles. Notably, although both tissue profiles were present, constructs that had been chondrogenically precultured prior to implantation showed a loss of glycosaminoglycan (GAG) as well as the presence of mineralization along with the formation of trabecula-like structures. In Study II of the study, the GAG loss and mineralization observed in Study I in vivo were recapitulated in vitro by the presence of either nearby bone or osteogenic culture medium additives but were prevented by a continued presence of chondrogenic medium additives. These data suggest conditions under which adult human stem cells in combination with polymer scaffolds synthesize functional and phenotypically distinct tissues based on the environmental conditions and highlight the potential influence that paracrine factors from adjacent bone may have on MSC fate, once implanted in vivo for chondral or osteochondral repair.
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Project description:Recently the role of macrophages on osteogenesis of mesenchymal stem cells (MSCs) is brought to focus. On the other hand, the cross-talk between macrophages and MSCs confirms that the paracrine molecules derived from macrophages are also carefully regulated by MSCs. Human umbilical cord mesenchymal stem cells (hucMSCs) could reduce secretions of inflammatory factors from macrophages for improving injury healing. hucMSC-derived extracellular matrix (hucMSC-ECM) exhibit nature similar to hucMSCs. It has been demonstrated that hucMSC-ECM possess considerable effects on reducing inflammatory response of macrophages, while the role of hucMSC-ECM on the expression of macrophage-derived paracrine osteogenic molecules is unclear. Here, we presented the decalcified bone scaffolds modified by hucMSC-derived extracellular matrix (DBM-ECM) maintaining multiple soluble cytokines including macrophage migration inhibitory factor (MIF). Compared with DBM, the DBM-ECM scaffolds induced bone formation in a macrophage-depending manner by an improved heterotopic ossification in SCID mice with or without macrophage depletion. Macrophage cocultured with the DBM-ECM expressed four osteoinductive cytokines (BMP2, FGF2, TGFβ3 and OSM), which were screen out by RNA sequencing, qPCR and western blot. The conditioned medium from macrophages cocultured with the DBM-ECM improved osteogenic differentiation of hBMSCs and activated CD74/CD44 signal transduction including phosphorylation of P38 and dephosphorylation of c-jun. Furthermore, the inhibitory effects of the DBM-ECM scaffolds with knockdown of MIF on osteogenesis in vitro and in vivo revealed that macrophage-mediated osteogenesis depends on MIF/CD74/ P38 signal transduction. This study indicates the coordinated crosstalk of macrophages and MSCs play a key role on bone regeneration induced by the DBM-ECM, with the emphasis on the constructing macrophage-derived osteoimmunological microenvironment.
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Project description:Off-the shelf small diameter vascular grafts are an attractive alternative to eliminate the need and shortcomings of autologous tissue for vascular grafting. Bovine saphenous vein (SV) extracellular matrix (ECM) scaffolds from are potentially ideal small diameter vascular grafts, due to their inherit architecture and signaling molecules capable of driving proper cell behavior and regeneration. However, harnessing this potential is predicated on the ability of the scaffold generation technique to maintain the delicate structure, composition and associated function of native vascular ECM. Previous decellularization methods have been uniformly demonstrated to distupt the delicate basement membrane (BM) components of native vascular ECM. Here we demonstrate bovine SV ECM scaffolds generated using the novel antigen removal (AR) approach results in retention of native BM protein composition (e.g., Collagen IV and laminin), structure and cell modulatory function. Presence of BM proteins in AR vascular ECM scaffolds increases endothelial cell migration and proliferation, appropriate formation of adherence junction and apicobasal polarization, increased secretion of nitric oxide, and modulates endothelial cell quiescence. We conclude that presence of intact native vascular BM in AR SV ECM scaffolds modulate human endothelial cell behaviors which are essential for vessel homeostasis.
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Project description:Synovium-derived mesenchymal stem cells (SMSCs) are an emerging cell source for regenerative medicine applications, including osteochondral defect (OCD) repair. However, in contrast to bone marrow MSCs, scaffold compositions which promote SMSC chondrogenesis/osteogenesis are still being identified. In the present manuscript, we examine poly(ethylene) glycol (PEG)-based scaffolds containing zonally-specific biochemical cues to guide SMSC osteochondral differentiation. Specifically, SMSCs were encapsulated in PEG-based scaffolds incorporating glycosaminoglycans (hyaluronan or chondroitin-6-sulfate [CSC]), low-dose of chondrogenic and osteogenic growth factors (TGFβ1 and BMP2, respectively), or osteoinductive poly(dimethylsiloxane) (PDMS). Initial studies suggested that PEG-CSC-TGFβ1 scaffolds promoted enhanced SMSC chondrogenic differentiation, as assessed by significant increases in Sox9 and aggrecan. Conversely, PEG-PDMS-BMP2 scaffolds stimulated increased levels of osteoblastic markers with significant mineral deposition. A "Transition" zone formulation was then developed containing a graded mixture of the chondrogenic and osteogenic signals present in the PEG-CSC-TGFβ1 and PEG-PDMS-BMP2 constructs. SMSCs within the "Transition" formulation displayed a phenotypic profile similar to hypertrophic chondrocytes, with the highest expression of collagen X, intermediate levels of osteopontin, and mineralization levels equivalent to "bone" formulations. Overall, these results suggest that a graded transition from PEG-CSC-TGFβ1 to PEG-PDMS-BMP2 scaffolds elicits a gradual SMSC phenotypic shift from chondrocyte to hypertrophic chondrocyte to osteoblast-like. As such, further development of these scaffold formulations for use in SMSC-based OCD repair is warranted. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2019-2029, 2019.
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