Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition

Zhu, Yuyan; Song, Xumei; Wang, Jian; Li, Yukui; Yang, Yinxue; Yang, Tingting; Ma, Hongwei; Wang, Yunlong; Zhang, Guangyi; Cho, William C.; Liu, Xiaoming; Wei, Jun

doi:10.1517/14712598.2015.960837

Cited by 27 publications

(19 citation statements)

References 57 publications

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“…In light of this, bulk manufacturing protocols for hAMSC and hCMSC with the ability to maintain vigorous growth and stable karyotypes will need to be developed if widespread clinical translation of their pro‐regenerative and pro‐reparative potential is to be realized. Given recent reports on the importance of MSC priming and impact of biomatrix stiffness on stem function , these factors should also be given due consideration in protocol development for bulk cutures.…”

Section: Yields and Growth Characteristicsmentioning

confidence: 99%

“…Unlike MSC from bone marrow and adipose tissues, expansion of hAMSC and hCMSC in vitro is contentious where some report poor expansion beyond five passages [43], and others report a stable karyotype after 20 passages over a period of 120 days [53]. Serial expansion of stem cells from gestational tissues, albeit with placental MSC, has also been previously shown to be associated with epigenetic alterations when the cells were passaged under serum-free conditions [54]. This may be a cause for concern since the dominant epigenetic changes observed were demethylation of genes associated with ageing and tumorigenesis.…”

Section: Yields and Growth Characteristicsmentioning

confidence: 99%

“…This may be a cause for concern since the dominant epigenetic changes observed were demethylation of genes associated with ageing and tumorigenesis. However, it should be noted that the reported epigenetic changes did not result in malignant transformation [54]. In light of this, bulk manufacturing protocols for hAMSC and hCMSC with the ability to maintain vigorous growth and stable karyotypes will need to be developed if widespread clinical translation of their pro-regenerative and pro-reparative potential is to be realized.…”

Section: Yields and Growth Characteristicsmentioning

confidence: 99%

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Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

Lim

2017

Stem Cells Translational Medicine

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The clinical application of the fetal membranes dates back to nearly a century. Their use has ranged from superficial skin dressings to surgical wound closure. The applications of the fetal membranes are constantly evolving, and key to this is the uncovering of multiple populations of stem and stem‐like cells, each with unique properties that can be exploited for regenerative medicine. In addition to pro‐angiogenic and immunomodulatory properties of the stem and stem‐like cells arising from the fetal membranes, the dehydrated and/or decellularized forms of the fetal membranes have been used to support the growth and function of other cells and tissues, including adipose‐derived mesenchymal stem cells. This concise review explores the biological origin of the fetal membranes, a history of their use in medicine, and recent developments in the use of fetal membranes and their derived stem and stem‐like cells in regenerative medicine. Stem Cells Translational Medicine 2017;6:1767–1776

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Section: Yields and Growth Characteristicsmentioning

confidence: 99%

Section: Yields and Growth Characteristicsmentioning

confidence: 99%

Section: Yields and Growth Characteristicsmentioning

confidence: 99%

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Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

Lim

2017

Stem Cells Translational Medicine

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“…The main prerequisite of stem cell-based therapies application is obtaining their adequate amount by expansion in vitro. The time of culture seem to be critical because several studies described changes of biological properties of stem cells during prolonged cultivation (Nava et al, 2015;Zhu et al, 2015). The present study was therefore aimed at analysis of selected biological and morphological properties of ATSCs during prolonged culture in vitro up to 10th passage.…”

Section: Discussionmentioning

confidence: 99%

Effect of Serial Passaging on the Morphology and Biological Characteristics of Human Adipose Tissue-derived Stem Cells

Oravcová¹,

Boháč²,

Krajčíová³

et al. 2016

OnLine Journal of Biological Sciences

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Somatic stem cells posses an exclusive property of self regeneration and plasticity which makes them promising candidates for use in tissue engineering and regenerative medicine. In the case of stem cell therapy it is crucial to obtain them in sufficient amount. That's why they have to be cultured under in vitro conditions. Long term culture provides adequate number of cells, but on the other hand it is associated with increased risk of spontaneous cell transformation. In this study we analyzed the effect of serial passaging (up to 10th passage) on the morphological and selected biological characteristics of human stem cells isolated from adipose tissue in respect to potential malignant transformation. Obtained results showed that human adipose tissue-derived stem cells maintained their morphological and biological properties during 10 passages and after performing further tests mainly addressed the cytogenetic stability and expression of regulators of cell cycle, senescence and apoptosis, they should be safely used in clinical practice.

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“…In vitro studies have indicated that MSCs derived from placenta of fetal origin possess greater therapeutic potential compared with MSCs isolated from other tissues and organs [1,2]. Several studies support the ability of these MSCs either to repair or regenerate damaged myocardium [3–5], although their long-term durability in tissue is controversial [6,7].…”

Section: Introductionmentioning

confidence: 99%

Persistence and proliferation of human mesenchymal stromal cells in the right ventricular myocardium after intracoronary injection in a large animal model of pulmonary hypertension

et al. 2017

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Background aims In this study, we demonstrate long-term persistence of human mesenchymal stromal cells (hMSCs) after intracoronary injection in a large animal model of pulmonary hypertension (PH). Methods Commercially available placenta-derived hMSCs were used. Experiments were conducted on 14 female Yorkshire swine. Four animals served as controls, and 10 underwent pulmonary vein (PV) banding. After 12 ± 2 weeks, PH and PV dysfunction were confirmed by right heart catheterization and cardiac magnetic resonance imaging. hMSCs were injected in the marginal branch of the right coronary artery. Tissues were harvested 6, 9 or 24 days after infusion. Results After 12 ± 2 weeks after PV banding, all subjects had increased mean pulmonary artery pressure (13.6 ± 3.6 versus 30.8 ± 4.5 mm Hg, P < 0.007) and a decrease in right ventricular ejection fraction from 51.7 ± 5.7% versus 30.5 ± 11.3% (P = 0.003). Intracoronary injection of hMSCs was well tolerated. Up to 24 days after hMSC injection, immunohistochemistry revealed extravascular viable human CD105+ mononuclear cells in the right ventricle (RV) that were Ki67+. This was confirmed by fluorescence in situ hybridization. CD45+ porcine inflammatory cells were identified, commonly seen adjacent to areas of healing microscopic infarction that likely dated to the time of the original hMSC injection. Anti-CD31 staining produced strong signals in areas of injected hMSCs. Immunohistochemistry staining for vascular cell adhesion molecule-1 showed upregulation in the clusters, where mononuclear cells were located. Conclusions hMSCs injected via intracoronary infusion survived up to 24 days and demonstrated proliferative capacity. hMSCs can persist long term in the RV and are potential cell source for tissue repair in RV dysfunction.

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Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition

Abstract: The fPMSCs cultured in serum-free medium have a tendency to deposit methylation modifications over in vitro expansion, therefore the detection of genetic and/or epigenetic alterations is necessary for fPMSCs before they are employed for clinical uses.

Cited by 27 publications

References 57 publications

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

Effect of Serial Passaging on the Morphology and Biological Characteristics of Human Adipose Tissue-derived Stem Cells

Persistence and proliferation of human mesenchymal stromal cells in the right ventricular myocardium after intracoronary injection in a large animal model of pulmonary hypertension

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