Single-cell profiles of human bone marrow-derived mesenchymal stromal cells after IFN-γ and TNF-α licensing

Gene ◽  
2021 ◽  
Vol 771 ◽  
pp. 145347
Author(s):  
Shuanglong Lu ◽  
Xiaohong Qiao
Keyword(s):  
Bone Marrow ◽  
Single Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals Strategies to Identify Mesenchymal Stromal Cells in Minimally Manipulated Human Bone Marrow Aspirate Concentrate Lack Consensus

2021 ◽  
pp. 036354652199378
Author(s):  
Severin Ruoss ◽  
J. Todd Walker ◽  
Chanond A. Nasamran ◽  
Kathleen M. Fisch ◽  
Conner J. Paez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bone Marrow Aspirate ◽  
Transcriptional Profile ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Background: There is a need to identify and quantify mesenchymal stromal cells (MSCs) in human bone marrow aspirate concentrate (BMAC) source tissues, but current methods to do so were established in cultured cell populations. Given that surface marker and gene expression change in cultured cells, it is doubtful that these strategies are valid to quantify MSCs in fresh BMAC. Purpose: To establish the presence, quantity, and heterogeneity of BMAC-derived MSCs in minimally manipulated BMAC using currently available strategies. Study Design: Descriptive laboratory study. Methods: Five published strategies to identify MSCs were compared for suitability and efficiency to quantify clinical-grade BMAC-MSCs and cultured MSCs at the single cell transcriptome level on BMAC samples being used clinically from 15 orthopaedic patients and on 1 cultured MSC sample. Strategies included (1) the guidelines by the International Society for Cellular Therapy (ISCT), (2) CD271 expression, (3) the Ghazanfari et al transcriptional profile, (4) the Jia et al transcriptional profile, and (5) the Silva et al transcriptional profile. Results: ISCT guidelines did not identify any MSCs in BMAC at the transcriptional level and only 1 in 9 million cells at the protein level. Of 12,850 BMAC cells, 9 expressed the CD271 gene. Only 116 of 396 Ghazanfari genes were detected in BMAC, whereas no cells expressed all of them. No cells expressed all Jia genes, but 25 cells expressed at least 13 of 22. No cells expressed all Silva genes, but 19 cells expressed at least 8 of 23. Most importantly, the liberalized strategies tended to identify different cells and most of them clustered with immune cells. Conclusion: Currently available methods need to be liberalized to identify any MSCs in fresh human BMAC and lack consensus at the single cell transcriptome and protein expression levels. These different cells should be isolated and challenged to establish phenotypic differences. Clinical Relevance: This study demonstrated that improved strategies to quantify MSC concentrations in BMAC for clinical applications are urgently needed. Until then, injected minimally manipulated MSC doses should be reported as rough estimates or as unknown.

scholarly journals Growth characteristics of human bone marrow mesenchymal stromal cells at cultivation on synthetic polyelectrolyte nanofilms in vitro

Heliyon ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e06517
Author(s):  
Lyudmila M. Mezhevikina ◽  
Dmitriy A. Reshetnikov ◽  
Maria G. Fomkina ◽  
Nurbol O. Appazov ◽  
Saltanat Zh. Ibadullayeva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Growth Characteristics ◽  
Human Bone ◽  
Human Bone Marrow

scholarly journals Human bone marrow-derived mesenchymal stromal cells cultured in serum-free media demonstrate enhanced antifibrotic abilities via prolonged survival and robust regulatory T cell induction in murine bleomycin-induced pulmonary fibrosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shun Takao ◽  
Taku Nakashima ◽  
Takeshi Masuda ◽  
Masashi Namba ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pulmonary Fibrosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Pulmonary Inflammation ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Distributed Data ◽  
Serum Free ◽  
Free Media

Abstract Background Mesenchymal stromal cells (MSCs) are a potential therapeutic tool for pulmonary fibrosis. However, ex vivo MSC expansion using serum poses risks of harmful immune responses or unknown pathogen infections in the recipients. Therefore, MSCs cultured in serum-free media (SF-MSCs) are ideal for clinical settings; however, their efficacy in pulmonary fibrosis is unknown. Here, we investigated the effects of SF-MSCs on bleomycin-induced pulmonary inflammation and fibrosis compared to those of MSCs cultured in serum-containing media (S-MSCs). Methods SF-MSCs and S-MSCs were characterized in vitro using RNA sequence analysis. The in vivo kinetics and efficacy of SF-MSC therapy were investigated using a murine model of bleomycin-induced pulmonary fibrosis. For normally distributed data, Student’s t test and one-way repeated measures analysis of variance followed by post hoc Tukey’s test were used for comparison between two groups and multiple groups, respectively. For non-normally distributed data, Kruskal–Wallis and Mann–Whitney U tests were used for comparison between groups, using e Bonferroni’s correction for multiple comparisons. All tests were two-sided, and P < 0.05 was considered statistically significant. Results Serum-free media promoted human bone marrow-derived MSC expansion and improved lung engraftment of intravenously administered MSCs in recipient mice. SF-MSCs inhibited the reduction in serum transforming growth factor-β1 and the increase of interleukin-6 in both the serum and the bronchoalveolar lavage fluid during bleomycin-induced pulmonary fibrosis. SF-MSC administration increased the numbers of regulatory T cells (Tregs) in the blood and lungs more strongly than in S-MSC administration. Furthermore, SF-MSCs demonstrated enhanced antifibrotic effects on bleomycin-induced pulmonary fibrosis, which were diminished by antibody-mediated Treg depletion. Conclusions SF-MSCs significantly suppressed BLM-induced pulmonary inflammation and fibrosis through enhanced induction of Tregs into the lungs and corrected the dysregulated cytokine balance. Therefore, SF-MSCs could be a useful tool for preventing pulmonary fibrosis progression without the demerits of serum use.

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