Characterisation of ovine bone marrow-derived stromal cells (oBMSC) and evaluation of chondrogenically induced micro-pellets for cartilage tissue repair in vivo
| Autor: | Kathryn Futrega, Ena Music, Ross Crawford, Pamela Gehron Robey, Stan Gronthos, Siamak Saifzadeh, Travis J. Klein, Michael R. Doran |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cartilage
Articular IBMX Stromal cell Medicine (miscellaneous) Bone Marrow Cells Pilot Projects Biochemistry Genetics and Molecular Biology (miscellaneous) lcsh:Biochemistry chemistry.chemical_compound Chondrocytes Bone Marrow Osteoarthritis medicine Animals lcsh:QD415-436 Micro-pellet Cells Cultured lcsh:R5-920 Sheep Research Cartilage Mesenchymal stem cell Bone marrow stromal cells Cell Differentiation Hypertrophy Cell Biology Chondrogenesis Cell biology Oxygen medicine.anatomical_structure chemistry Adipogenesis Differentiation Molecular Medicine Mesenchymal stem cells Bone marrow Stem cell lcsh:Medicine (General) |
| Zdroj: | Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-19 (2021) Stem Cell Research & Therapy |
| ISSN: | 1757-6512 |
| Popis: | Abstract Bone marrow stromal cells (BMSC) show promise in cartilage repair, and sheep are the most common large animal pre-clinical model. Objective The objective of this study was to characterise ovine BMSC (oBMSC) in vitro, and to evaluate the capacity of chondrogenic micro-pellets manufactured from oBMSC or ovine articular chondrocytes (oACh) to repair osteochondral defects in sheep. Design oBMSC were characterised for surface marker expression using flow cytometry and evaluated for tri-lineage differentiation capacity. oBMSC micro-pellets were manufactured in a microwell platform, and chondrogenesis was compared at 2%, 5%, and 20% O2. The capacity of cartilage micro-pellets manufactured from oBMSC or oACh to repair osteochondral defects in adult sheep was evaluated in an 8-week pilot study. Results Expanded oBMSC were positive for CD44 and CD146 and negative for CD45. The common adipogenic induction ingredient, 3-Isobutyl-1-methylxanthine (IBMX), was toxic to oBMSC, but adipogenesis could be restored by excluding IBMX from the medium. BMSC chondrogenesis was optimal in a 2% O2 atmosphere. Micro-pellets formed from oBMSC or oACh appeared morphologically similar, but hypertrophic genes were elevated in oBMSC micro-pellets. While oACh micro-pellets formed cartilage-like repair tissue in sheep, oBMSC micro-pellets did not. Conclusion The sensitivity of oBMSC, compared to human BMSC, to IBMX in standard adipogenic assays highlights species-associated differences. Micro-pellets manufactured from oACh were more effective than micro-pellets manufactured from oBMSC in the repair of osteochondral defects in sheep. While oBMSC can be driven to form cartilage-like tissue in vitro, the effective use of these cells in cartilage repair will depend on the successful mitigation of hypertrophy and tissue integration. |
| Databáze: | OpenAIRE |
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