Hypoxia-induced amniotic fluid stem cell secretome augments cardiomyocyte proliferation and enhances cardioprotective effects under hypoxic-ischemic conditions

Kukumberg, Marek; Phermthai, Tatsanee; Wichitwiengrat, Suparat; Wang, Xiaoyuan; Subramanian, Arjunan; Chong, Suet Yen; Fong, Chui‐Yee; Wang, Jiong‐Wei; Rufaihah, Abdul Jalil; Mattar, Citra Nurfarah Zaini

doi:10.1038/s41598-020-80326-w

Cited by 17 publications

(10 citation statements)

References 68 publications

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“…The rationale comes from studies demonstrating that systemic injection of hAFSC-conditioned medium can provide prompt cardioprotective effects, by decreasing infarct size and enhancing myocardial cell survival in a rat model of acute ischaemia-reperfusion injury [ 53 ]. Similar cardioprotective and stimulatory paracrine effects from the secretome of human amniotic fluid progenitors were also obtained by follow-up studies based on models of doxorubicin-induced cardiotoxicity both in vitro and in vivo [ 51 , 52 ] and from independent work in a myocardial ischemia-reperfusion (I/R) injury mouse model [ 78 ]. In particular, myocardial infarction (MI) can often lead to the onset of heart failure (HF), which afflicts up to 38 million people in the world [ 79 ].…”

Section: Evs From Human Amniotic Fluid Stem Cells As Promising Medicinal Therapeuticsmentioning

confidence: 59%

Small Extracellular Vesicles from Human Amniotic Fluid Samples as Promising Theranostics

Costa

Quarto

2022

IJMS

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Since the first evidence that stem cells can provide pro-resolving effects via paracrine secretion of soluble factors, growing interest has been addressed to define the most ideal cell source for clinical translation. Leftover or clinical waste samples of human amniotic fluid obtained following prenatal screening, clinical intervention, or during scheduled caesarean section (C-section) delivery at term have been recently considered an appealing source of mesenchymal progenitors with peculiar regenerative capacity. Human amniotic fluid stem cells (hAFSC) have been demonstrated to support tissue recovery in several preclinical models of disease by exerting paracrine proliferative, anti-inflammatory and regenerative influence. Small extracellular vesicles (EVs) concentrated from the hAFSC secretome (the total soluble trophic factors secreted in the cell-conditioned medium, hAFSC-CM) recapitulate most of the beneficial cell effects. Independent studies in preclinical models of either adult disorders or severe diseases in newborns have suggested a regenerative role of hAFSC-EVs. EVs can be eventually concentrated from amniotic fluid (hAF) to offer useful prenatal information, as recently suggested. In this review, we focus on the most significant aspects of EVs obtained from either hAFSC and hAF and consider the current challenges for their clinical translation, including isolation, characterization and quantification methods.

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Section: Evs From Human Amniotic Fluid Stem Cells As Promising Medicinal Therapeuticsmentioning

confidence: 59%

Small Extracellular Vesicles from Human Amniotic Fluid Samples as Promising Theranostics

Costa

Quarto

2022

IJMS

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“…For this reason, we further tested the secretome of hAFSCs upon neural differentiation induction with this particular chemical combination. Recent studies by other authors (Kukumberg et al, 2021) showed that hAFSCs under hypoxic conditions, in comparison to normoxic state, secrete larger quantities of growth factors such as BDNF and VEGF. Results of our ELISA analysis revealed that secretion of BDNF and VEGF proteins is also increased after the induction of neurogenic differentiation by a comparable degree in hAFSCs from both normal and pathological pregnancies (Figures 8C,D).…”

Section: Discussionmentioning

confidence: 95%

Metabolic Profile and Neurogenic Potential of Human Amniotic Fluid Stem Cells From Normal vs. Fetus-Affected Gestations

Valiulienė

Zentelytė

Beržanskytė

et al. 2021

Front. Cell Dev. Biol.

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Human amniotic fluid stem cells (hAFSCs) possess some characteristics with mesenchymal stem cells (MSCs) and embryonic stem cells and have a broader differentiation potential compared to MSCs derived from other sources. Although hAFSCs are widely researched, their analysis mainly involves stem cells (SCs) obtained from normal, fetus-unaffected gestations. However, in clinical settings, knowledge about hAFSCs from normal gestations could be poorly translational, as hAFSCs from healthy and fetus-diseased gestations may differ in their differentiation and metabolic potential. Therefore, a more thorough investigation of hAFSCs derived from pathological gestations would provide researchers with the knowledge about the general characteristics of these cells that could be valuable for further scientific investigations and possible future clinical applicability. The goal of this study was to look into the neurogenic and metabolic potential of hAFSCs derived from diseased fetuses, when gestations were concomitant with polyhydramnios and compare them to hAFSCs derived from normal fetuses. Results demonstrated that these cells are similar in gene expression levels of stemness markers (SOX2, NANOG, LIN28A, etc.). However, they differ in expression of CD13, CD73, CD90, and CD105, as flow cytometry analysis revealed higher expression in hAFSCs from unaffected gestations. Furthermore, hAFSCs from “Normal” and “Pathology” groups were different in oxidative phosphorylation rate, as well as level of ATP and reactive oxygen species production. Although the secretion of neurotrophic factors BDNF and VEGF was of comparable degree, as evaluated with enzyme-linked immunosorbent assay (ELISA) test, hAFSCs from normal gestations were found to be more prone to neurogenic differentiation, compared to hAFSCs from polyhydramnios. Furthermore, hAFSCs from polyhydramnios were distinguished by higher secretion of pro-inflammatory cytokine TNFα, which was significantly downregulated in differentiated cells. Overall, these observations show that hAFSCs from pathological gestations with polyhydramnios differ in metabolic and inflammatory status and also possess lower neurogenic potential compared to hAFSCs from normal gestations. Therefore, further in vitro and in vivo studies are necessary to dissect the potential of hAFSCs from polyhydramnios in stem cell-based therapies. Future studies should also search for strategies that could improve the characteristics of hAFSCs derived from diseased fetuses in order for those cells to be successfully applied for regenerative medicine purposes.

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“…Indeed, a growing body of research confirms the positive effects of hypoxic cultivations on MSCs isolated from different tissues [ 73 , 74 , 75 , 76 ]. It was demonstrated that expansion in low oxygen concentrations or priming with hypoxia increases the expression of growth factors [ 77 ], pro‐angiogenic and anti‐inflammatory factors [ 78 ], the biological activity of extracellular vesicles [ 76 ], proliferation rates [ 73 , 79 ] and self‐renewal capacity [ 80 ] of MSCs from different sources. Using adipose tissue‐derived MSCs which were modified with genetically encoded hypoxia sensors, it was demonstrated that HIF‐1a is stabilized in these cells starting from 7.5% O 2 in incubator overlay [ 81 ].…”

Section: Influence and Importance Of Hypoxic Cultivation Conditionsmentioning

confidence: 99%

Physiologic isolation and expansion of human mesenchymal stem/stromal cells for manufacturing of cell‐based therapy products

Egger

Lavrentieva

Kugelmeier³

et al. 2021

Engineering in Life Sciences

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The utilization of mesenchymal stem/stromal cells raises new hopes in treatment of diseases and pathological conditions, while at the same time bringing immense challenges for researchers, manufacturers and physicians. It is essential to consider all steps along the in vitro fabrication of cell-based products in order to reach efficient and reproducible treatment outcomes. Here, the optimal protocols for isolation, cultivation and differentiation of mesenchymal stem cells are required. In this review we discuss these aspects and their influence on the final cell-based product quality. We demonstrate that physiological in vitro cell cultivation conditions play a crucial role in therapeutic functionalities of cultivated cells. We show that three-dimensional cell culture, dynamic culture conditions and physiologically relevant in vitro oxygen concentrations during isolation and expansion make a decisive contribution towards the improvement of cell-based products in regenerative medicine.

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Hypoxia-induced amniotic fluid stem cell secretome augments cardiomyocyte proliferation and enhances cardioprotective effects under hypoxic-ischemic conditions

Cited by 17 publications

References 68 publications

Small Extracellular Vesicles from Human Amniotic Fluid Samples as Promising Theranostics

Small Extracellular Vesicles from Human Amniotic Fluid Samples as Promising Theranostics

Metabolic Profile and Neurogenic Potential of Human Amniotic Fluid Stem Cells From Normal vs. Fetus-Affected Gestations

Physiologic isolation and expansion of human mesenchymal stem/stromal cells for manufacturing of cell‐based therapy products

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