Recovery and maintenance of NESTIN expression in umbilical cord-MSC using a novel culture medium

Liu, Yuncheng; Xiao, Feidi; Hu, Xiang; Tang, Zan; Fu, Zeqin; Liang, Xiao; Zeng, Guifang; Zeng, Weijie; Liao, Yan; Ren, Yuan; Liu, Zhiyu; Peng, Hao; Mei, Qiuhong; Liu, Muyun

doi:10.1186/s13568-020-01067-7

Cited by 4 publications

(7 citation statements)

References 40 publications

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“…Nestin is a class VI intermediate filament protein, which is usually expressed by stem-like cells, including neural stem or progenitor cells (Bernal and Arranz, 2018), tumor stem cells (Neradil and Veselska, 2015) and MSCs of various tissues (Yin et al, 2016;Lu et al, 2019;Liao et al, 2020). Nestin functions are associated with the self-renewal, proliferation, differentiation and migration of stem cells, and previous research reports that Nestin expression gradually decreases with increasing MSCs passage (Liu et al, 2020). In the current study we found higher Nestin expression in the hPL-UCMSCs group than FBS-UCMSCs at P4, which may be the cause of group differences in cell proliferation, senescence, and differentiation.…”

Section: Discussionmentioning

confidence: 99%

Human Platelet Lysate Maintains Stemness of Umbilical Cord-Derived Mesenchymal Stromal Cells and Promote Lung Repair in Rat Bronchopulmonary Dysplasia

Liao

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stromal cells (MSCs) show potential for treating preclinical models of newborn bronchopulmonary dysplasia (BPD), but studies of their therapeutic effectiveness have had mixed results, in part due to the use of different media supplements for MSCs expansion in vitro. The current study sought to identify an optimal culture supplement of umbilical cord-derived MSCs (UC-MSCs) for BPD therapy. In this study, we found that UC-MSCs cultured with human platelet lysate (hPL-UCMSCs) were maintained a small size from Passage 1 (P1) to P10, while UC-MSCs cultured with fetal bovine serum (FBS-UCMSCs) became wide and flat. Furthermore, hPL was associated with lower levels of senescence in UC-MSCs during in vitro expansion compared with FBS, as indicated by the results of β-galactosidase staining and measures of senescence-related genes (CDKN2A, CDKN1A, and mTOR). In addition, hPL enhanced the proliferation and cell viability of the UC-MSCs and reduced their doubling time in vitro. Compared with FBS-UCMSCs, hPL-UCMSCs have a greater potential to differentiate into osteocytes and chondrocytes. Moreover, using hPL resulted in greater expression of Nestin and specific paracrine factors (VEGF, TGF-β1, FGF2, IL-8, and IL-6) in UC-MSCs compared to using FBS. Critically, we also found that hPL-UCMSCs are more effective than FBS-UCMSCs for the treatment of BPD in a rat model, with hPL leading to improvements in survival rate, lung architecture and fibrosis, and lung capillary density. Finally, qPCR of rat lung mRNA demonstrated that hPL-UCMSCs had lower expression levels of inflammatory factors (TNF-α and IL-1β) and a key chemokine (MCP-1) at postnatal day 10, and there was significant reduction of CD68+ macrophages in lung tissue after hPL-UCMSCs transplantation. Altogether, our findings suggest that hPL is an optimal culture supplement for UC-MSCs expansion in vitro, and that hPL-UCMSCs promote lung repair in rat BPD disease.

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Section: Discussionmentioning

confidence: 99%

Human Platelet Lysate Maintains Stemness of Umbilical Cord-Derived Mesenchymal Stromal Cells and Promote Lung Repair in Rat Bronchopulmonary Dysplasia

Liao

et al. 2021

Front. Cell Dev. Biol.

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“…Comparison of MSCs from BM, UC, and UC blood found all expressed similar markers, yet only UC-MSCs and UC blood MSCs did not express HLA-DR associated with transplant rejection, making them more similar to AD-MSCs [ 99 ]. Although, UC-MSCs express nestin early after isolation, their expression declines with passage [ 100 , 101 ]. This reduction in nestin expression correlated with reduced anti-inflammatory capacity later in passage [ 101 ].…”

Section: Umbilical-cord-derived Mesenchymal Stromal Cells (Uc-mscs)mentioning

confidence: 99%

“…Although, UC-MSCs express nestin early after isolation, their expression declines with passage [ 100 , 101 ]. This reduction in nestin expression correlated with reduced anti-inflammatory capacity later in passage [ 101 ]. In addition, cell surface marker expression is thought to change in passage and may indicate epigenetic phenomena associated with cell culture [ 102 ].…”

Section: Umbilical-cord-derived Mesenchymal Stromal Cells (Uc-mscs)mentioning

confidence: 99%

“…Like other MSC types, UC-MSCs are traditionally expanded using media containing serum, which due to the presence of xenogeneic materials is not compliant with future GMP manufacture. Clinically, the use of human autologous serum and/or platelet lysate can be used instead of serum, and UM-MSCs grown in UltraGRO TM , a xenofree alternative to FBS, have better anti-inflammatory performance, correlating with retained nestin expression [ 101 ]. In theory, these cells may be stored to provide stem cells for therapeutic use decades later, though the phenotype would need to be tightly defined and reproduced post thaw to meet GMP compliance.…”

Section: Umbilical-cord-derived Mesenchymal Stromal Cells (Uc-mscs)mentioning

confidence: 99%

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Therapeutic Potential of Niche-Specific Mesenchymal Stromal Cells for Spinal Cord Injury Repair

Lindsay

Barnett

2021

Cells

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The use of mesenchymal stem/stromal cells (MSCs) for transplant-mediated repair represents an important and promising therapeutic strategy after spinal cord injury (SCI). The appeal of MSCs has been fuelled by their ease of isolation, immunosuppressive properties, and low immunogenicity, alongside the large variety of available tissue sources. However, despite reported similarities in vitro, MSCs sourced from distinct tissues may not have comparable biological properties in vivo. There is accumulating evidence that stemness, plasticity, immunogenicity, and adaptability of stem cells is largely controlled by tissue niche. The extrinsic impact of cellular niche for MSC repair potential is therefore important, not least because of its impact on ex vivo expansion for therapeutic purposes. It is likely certain niche-targeted MSCs are more suited for SCI transplant-mediated repair due to their intrinsic capabilities, such as inherent neurogenic properties. In addition, the various MSC anatomical locations means that differences in harvest and culture procedures can make cross-comparison of pre-clinical data difficult. Since a clinical grade MSC product is inextricably linked with its manufacture, it is imperative that cells can be made relatively easily using appropriate materials. We discuss these issues and highlight the importance of identifying the appropriate niche-specific MSC type for SCI repair.

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“…As depicted in Table 1 , different culture media without foetal bovine serum (FBS) have been used by Kang JY et al [ 58 ], Wu X et al [ 59 ], and Liu Y et al [ 60 ] during the ex vivo expansion of the MSCs. These authors observed enhanced immunomodulatory effects of MSCs in in vivo models of IBD, thus reducing the risk of xenoimmunization and zoonotic transmission.…”

Section: Strategies To Boost Msc-based Therapy In Ibdmentioning

confidence: 99%

Improving the Efficacy of Mesenchymal Stem/Stromal-Based Therapy for Treatment of Inflammatory Bowel Diseases

López‐Santalla

Garín

2021

Biomedicines

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Inflammatory bowel diseases (IBD) consisting of persistent and relapsing inflammatory processes of the intestinal mucosa are caused by genetic, environmental, and commensal microbiota factors. Despite recent advances in clinical treatments aiming to decrease inflammation, nearly 30% of patients treated with biologicals experienced drawbacks including loss of response, while others can develop severe side effects. Hence, novel effective treatments are highly needed. Mesenchymal stem/stromal cell (MSCs) therapy is an innovative therapeutic alternative currently under investigation for IBD. MSCs have the inherent capacity of modulating inflammatory immune responses as well as regenerating damaged tissues and are therefore a prime candidate to use as cell therapy in patients with IBD. At present, MSC-based therapy has been shown preclinically to modulate intestinal inflammation, whilst the safety of MSC-based therapy has been demonstrated in clinical trials. However, the successful results in preclinical studies have not been replicated in clinical trials. In this review, we will summarize the protocols used in preclinical and clinical trials and the novel approaches currently under investigation which aim to increase the beneficial effects of MSC-based therapy for IBD.

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Recovery and maintenance of NESTIN expression in umbilical cord-MSC using a novel culture medium

Cited by 4 publications

References 40 publications

Human Platelet Lysate Maintains Stemness of Umbilical Cord-Derived Mesenchymal Stromal Cells and Promote Lung Repair in Rat Bronchopulmonary Dysplasia

Human Platelet Lysate Maintains Stemness of Umbilical Cord-Derived Mesenchymal Stromal Cells and Promote Lung Repair in Rat Bronchopulmonary Dysplasia

Therapeutic Potential of Niche-Specific Mesenchymal Stromal Cells for Spinal Cord Injury Repair

Improving the Efficacy of Mesenchymal Stem/Stromal-Based Therapy for Treatment of Inflammatory Bowel Diseases

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