Effects of long-term culture on the biological characteristics and RNA profiles of human bone-marrow-derived mesenchymal stem cells

Wang, Shan; Wang, Ziming; Su, Huilan; Chen, Fenglei; Ma, Mengjun; Yu, Wenhui; Ye, Guiwen; Cen, Shuizhong; Mi, Rujia; Wu, Xiaohua; Deng, Wen; Feng, Pei; Zeng, Chengli; Shen, Huiyong; Wu, Yanfeng

doi:10.1016/j.omtn.2021.08.013

Cited by 28 publications

(23 citation statements)

References 64 publications

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“…In addition, many studies including our previous reports suggest that tissue repair and regeneration might be in part mediated by other EV components, such as miRNAs [7][8][9]. Indeed, the expression of miRNAs changes depending on its passage, as previously reported [32][33][34]. Thus, the functional EV components including miR-NAs, which are transferred to the injury site via the MSC-EVs, might be different in MSC-EVs at passages 5 and 12.…”

Section: Discussionmentioning

confidence: 58%

The therapeutic capacity of bone marrow MSC‐derived extracellular vesicles in Achilles tendon healing is passage‐dependent and indicated by specific glycans

et al. 2022

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The therapeutic potential of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) for various diseases and tissue repair is attracting attention. Here, EVs from conditioned medium of human bone marrow MSCs at passage 5 (P5) and passage 12 (P12) were analysed using mouse Achilles tendon rupture model and lectin microarray. P5 MSC-EVs accelerated Achilles tendon healing compared with P12 MSC-EVs. Fucose-specific lectin TJA-II was indicated as a glycan marker for therapeutic MSC-EVs. The present study demonstrated that early passaged MSC-EVs promote Achilles tendon healing compared with senescent MSC-EVs. Glycans on MSC-EVs might provide useful tools to establish a quality control and isolation system for therapeutic MSC-EVs in regenerative medicine.

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Section: Discussionmentioning

confidence: 58%

The therapeutic capacity of bone marrow MSC‐derived extracellular vesicles in Achilles tendon healing is passage‐dependent and indicated by specific glycans

et al. 2022

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“…However, there are still some problems; for example, due to technical limitations, there are certain difficulties in obtaining and preserving cells. As a donor ages, the number and function of MSCs also decline [21]. It was also found that MSCs are short-lived after systemic administration.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Preconditioned Extracellular Vesicles from Mesenchymal Stem Cells Improve Cartilage Repair in Osteoarthritis

Zhang

Tian

et al. 2022

Membranes

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In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and extracellular vesicles (EVs) may play a major role in the efficacy of this treatment. Hypoxia can change the cargo and biological functions of MSC-derived EVs (MSC-EVs). The aim of the present study was to determine whether the effects of hypoxia-preconditioned MSC-EVs on OA cartilage repair are superior to normoxia-preconditioned MSC-EVs. By using in vitro and in vivo OA models, we verified that hypoxia-preconditioned MSC-EVs improved chondrocyte proliferation and migration and suppressed chondrocyte apoptosis to a greater extent than normoxia-preconditioned MSC-EVs. Furthermore, we found that hypoxia altered the microRNA expression in MSC-EVs and identified four differentially expressed microRNAs: hsa-miR-181c-5p, hsa-miR-18a-3p, hsa-miR-376a-5p, and hsa-miR-337-5p. Bioinformatics analysis revealed that hypoxic pretreatment may promote cartilage repair by stimulating chondrocyte proliferation and migration and suppressing chondrocyte apoptosis through the miRNA-18-3P/JAK/STAT or miRNA-181c-5p/MAPK signaling pathway. Therefore, hypoxia-preconditioned EVs may be a novel treatment for OA.

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“…(a) Growth kinetics (cumulative population doublings, CPD) of bmMSCs and ucMSCs over 17 weeks of in vitro expansion (de Witte et al, 2017 ). (b) Quantification of Adipogenic differentiation (ORO staining); (c) quantification of osteogenic differentiation (ARS staining); (d) quantification of senescence (percent of SA‐β‐gal staining) at P4, P6, P8, P10, and P12 (e) (Wang et al, 2021 ). Relative telomere length detection of MSCs in P4, P6, and P12.…”

Section: Functional and Phenotypic Changes In Mscs ...mentioning

confidence: 99%

“…n = 9 MSCs per passage. Figure created by combining data from de Witte et al ( 2017 ) (a) and Wang et al, 2021 (b–e).…”

Section: Functional and Phenotypic Changes In Mscs ...mentioning

confidence: 99%

Cellular expansion of MSCs: Shifting the regenerative potential

et al. 2022

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Mesenchymal‐derived stromal or progenitor cells, commonly called “MSCs,” have attracted significant clinical interest for their remarkable abilities to promote tissue regeneration and reduce inflammation. Recent studies have shown that MSCs' therapeutic effects, originally attributed to the cells' direct differentiation capacity into the tissue of interest, are largely driven by the biomolecules the cells secrete, including cytokines, chemokines, growth factors, and extracellular vesicles containing miRNA. This secretome coordinates upregulation of endogenous repair and immunomodulation in the local microenvironment through crosstalk of MSCs with host tissue cells. Therapeutic applications for MSCs and their secretome‐derived products often involve in vitro monolayer expansion. However, consecutive passaging of MSCs significantly alters their therapeutic potential, inducing a broad shift from a pro‐regenerative to a pro‐inflammatory phenotype. A consistent by‐product of in vitro expansion of MSCs is the onset of replicative senescence, a state of cell arrest characterized by an increased release of proinflammatory cytokines and growth factors. However, little is known about changes in the secretome profile at different stages of in vitro expansion. Some culture conditions and bioprocessing techniques have shown promise in more effectively retaining the pro‐regenerative and anti‐inflammatory MSC phenotype throughout expansion. Understanding how in vitro expansion conditions influence the nature and function of MSCs, and their associated secretome, may provide key insights into the underlying mechanisms driving these alterations. Elucidating the dynamic and diverse changes in the MSC secretome at each stage of in vitro expansion is a critical next step in the development of standardized, safe, and effective MSC‐based therapies.

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Effects of long-term culture on the biological characteristics and RNA profiles of human bone-marrow-derived mesenchymal stem cells

Cited by 28 publications

References 64 publications

The therapeutic capacity of bone marrow MSC‐derived extracellular vesicles in Achilles tendon healing is passage‐dependent and indicated by specific glycans

The therapeutic capacity of bone marrow MSC‐derived extracellular vesicles in Achilles tendon healing is passage‐dependent and indicated by specific glycans

Hypoxia-Preconditioned Extracellular Vesicles from Mesenchymal Stem Cells Improve Cartilage Repair in Osteoarthritis

Cellular expansion of MSCs: Shifting the regenerative potential

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