Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head

Cytotherapy ◽  
2016 ◽  
Vol 18 (9) ◽  
pp. 1087-1099 ◽  
Author(s):  
Gabriela Ciapetti ◽  
Donatella Granchi ◽  
Caterina Fotia ◽  
Lucia Savarino ◽  
Dante Dallari ◽  
...  
2020 ◽  
Vol 30 (2_suppl) ◽  
pp. 3-12
Author(s):  
Martina Rocchi ◽  
Nicoladrea Del Piccolo ◽  
Alessandro Mazzotta ◽  
Gianluca Giavaresi ◽  
Milena Fini ◽  
...  

Introduction: Avascular necrosis of femoral head (AVN) is 1 of the main factors causing disability in young adults. Hip prosthesis can be considered an effective treatment of the painful symptoms but it is a major surgical intervention for this type of population. Thus, a large space should be left to therapeutic alternatives such as regenerative medicine. This retrospective study evaluates 52 AVN treated by core decompression, bone chips allograft, fibrin platelet-rich plasma (PRF) and concentrated autologous mesenchymal stromal cells (MSCs). Methods: The AVN was diagnosed using magnetic resonance imaging (MRI) and graded according to ARCO classification: a patient was classified stage 1 (21 patients), stage 3 (26 patients), and 4 patients were classified as stage 4. We evaluated patients with functional scores (Harris Hip Score) and radiological analysis at 3, 6, 12 and 24 months after the procedure. Patients requiring prosthetic replacement of the joint were included; in these cases, follow-up was interrupted at the time of the joint replacement procedure. Results: Our statistical analysis showed differences between survived and failed treatments, in terms of patient profile and ARCO radiological classification. The best result occurred in patients with ARCO grades 1 and 2, while the more advanced grades showed a high failure rate. It is interesting to note that ARCO quantification, conceived as the joint surface involved in the necrosis, has a negative influence on the outcome of the procedure. Indeed, patients affected by ARCO 3a, where necrosis involved a small portion of the femoral epiphysis and the collapse of the articular surface was limited to 2 mm, showed results similar to those obtained in patients with ARCO 1 and 2. Conclusions: In conclusion, compared with the alternative technique of decompression, our data suggest that post-collapse cases with a small area of necrosis and the use of bone grafts may show better results compared to those of the literature.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lizhen Liu ◽  
Kaimin Hu ◽  
Jingjing Feng ◽  
Huafang Wang ◽  
Shan Fu ◽  
...  

Abstract Background Isocitrate dehydrogenase (IDH1/2) gene mutations are the most frequently observed mutations in cartilaginous tumors. The mutant IDH causes elevation in the levels of R-enantiomer of 2-hydroxylglutarate (R-2HG). Mesenchymal stromal cells (MSCs) are reasonable precursor cell candidates of cartilaginous tumors. This study aimed to investigate the effect of oncometabolite R-2HG on MSCs. Methods Human bone marrow MSCs treated with or without R-2HG at concentrations 0.1 to 1.5 mM were used for experiments. Cell Counting Kit-8 was used to detect the proliferation of MSCs. To determine the effects of R-2HG on MSC differentiation, cells were cultured in osteogenic, chondrogenic and adipogenic medium. Specific staining approaches were performed and differentiation-related genes were quantified. Furthermore, DNA methylation status was explored by Illumina array-based arrays. Real-time PCR was applied to examine the signaling component mRNAs involved in. Results R-2HG showed no influence on the proliferation of human MSCs. R-2HG blocked osteogenic differentiation, whereas promoted adipogenic differentiation of MSCs in a dose-dependent manner. R-2HG inhibited chondrogenic differentiation of MSCs, but increased the expression of genes related to chondrocyte hypertrophy in a lower concentration (1.0 mM). Moreover, R-2HG induced a pronounced DNA hypermethylation state of MSC. R-2HG also improved promotor methylation of lineage-specific genes during osteogenic and chondrogenic differentiation. In addition, R-2HG induced hypermethylation and decreased the mRNA levels of SHH, GLI1and GLI2, indicating Sonic Hedgehog (Shh) signaling inhibition. Conclusions The oncometabolite R-2HG dysregulated the chondrogenic and osteogenic differentiation of MSCs possibly via induction of DNA hypermethylation, improving the role of R-2HG in cartilaginous tumor development.


2021 ◽  
Vol 28 (10) ◽  
pp. 1708-1725
Author(s):  
Mauro Krampera ◽  
Katarina Le Blanc

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