Anti-senescence ion-delivering nanocarrier for recovering therapeutic properties of long-term-cultured human adipose-derived stem cells

Abstract Background Human adipose-derived stem cells (hADSCs) have been used in various fields of tissue engineering because of their promising therapeutic efficacy. However, the stemness of hADSCs cannot be maintained for long durations, and their therapeutic cellular functions, such as paracrine factor secretion decrease during long-term cell culture. To facilitate the use of long-term-cultured hADSCs (L-ADSCs), we designed a novel therapeutic anti-senescence ion-delivering nanocarrier (AIN) that is capable of recovering the therapeutic properties of L-ADSCs. In the present study, we introduced a low-pH-responsive ion nanocarrier capable of delivering transition metal ions that can enhance angiogenic paracrine factor secretion from L-ADSCs. The AINs were delivered to L-ADSCs in an intracellular manner through endocytosis. Results Low pH conditions within the endosomes induced the release of transition metal ions (Fe) into the L-ADSCs that in turn caused a mild elevation in the levels of reactive oxygen species (ROS). This mild elevation in ROS levels induced a downregulation of senescence-related gene expression and an upregulation of stemness-related gene expression. The angiogenic paracrine factor secretion from L-ADSCs was significantly enhanced, and this was evidenced by the observed therapeutic efficacy in response to treatment of a wound-closing mouse model with conditioned medium obtained from AIN-treated L-ADSCs that was similar to that observed in response to treatment with short-term-cultured adipose-derived stem cells. Conclusions This study suggests a novel method and strategy for cell-based tissue regeneration that can overcome the limitations of the low stemness and therapeutic efficacy of stem cells that occurs during long-term cell culture. Graphical Abstract

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Cardioprotective effects of rat adipose‑derived stem cells differ under normoxic/physioxic conditions and are�associated with paracrine factor secretion

International Journal of Molecular Medicine ◽

10.3892/ijmm.2020.4524 ◽

2020 ◽

Cited By ~ 1

Author(s):

Yuanyuan Lin ◽

Xuewen Li ◽

Chunhui Fan ◽

Fan Yang ◽

Dajie Hao ◽

...

Keyword(s):

Stem Cells ◽

Adipose Derived Stem Cells ◽

Paracrine Factor ◽

Cardioprotective Effects ◽

Factor Secretion

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Long term culture and differentiation of endothelial progenitor like cells from rat adipose derived stem cells

Cytotechnology ◽

10.1007/s10616-017-0155-7 ◽

2017 ◽

Vol 70 (1) ◽

pp. 397-413 ◽

Cited By ~ 1

Author(s):

Monire Amerion ◽

Mojtaba Rezazadeh Valojerdi ◽

Saeid Abroun ◽

Mehdi Totonchi

Keyword(s):

Stem Cells ◽

Adipose Derived Stem Cells ◽

Endothelial Progenitor ◽

Long Term Culture

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Labeling of adipose-derived stem cells with quantum dots provides stable and long-term fluorescent signal for ex vivo cell tracking

In Vitro Cellular & Developmental Biology - Animal ◽

10.1007/s11626-016-0121-2 ◽

2016 ◽

Vol 53 (4) ◽

pp. 363-370 ◽

Cited By ~ 4

Author(s):

Clautina R. M. Costa ◽

Matheus L. T. Feitosa ◽

Dayseanny O. Bezerra ◽

Yulla K. P. Carvalho ◽

Rodrigo F. G. Olivindo ◽

...

Keyword(s):

Stem Cells ◽

Quantum Dots ◽

Cell Tracking ◽

Ex Vivo ◽

Adipose Derived Stem Cells ◽

Fluorescent Signal

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The Crosstalk of Adipose-Derived Stem Cells (ADSC), Oxidative Stress, and Inflammation in Protective and Adaptive Responses

International Journal of Molecular Sciences ◽

10.3390/ijms21239262 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9262

Author(s):

Luc Rochette ◽

Loubna Mazini ◽

Gabriel Malka ◽

Marianne Zeller ◽

Yves Cottin ◽

...

Keyword(s):

Stem Cells ◽

Intracellular Signaling ◽

Adipose Derived Stem Cells ◽

Adaptive Responses ◽

Complex Signals ◽

Beneficial Effects ◽

Secondary Messenger ◽

Secreted Factors ◽

Oxidation Reduction ◽

Therapeutic Properties

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which mediate the oxidation-reduction state of cells as a secondary messenger. ADSC therapy has demonstrated beneficial effects, suggesting that secreted factors may provide protection. There is evidence that ADSCs secrete a number of cytokines, growth factors, and antioxidant factors into their microenvironment, thus regulating intracellular signaling pathways in neighboring cells. In this review, we introduce the roles of ADSCs in the protection of cells by modulating inflammation and immunity, and we develop their potential therapeutic properties.

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First Insights into the Effect of Low-Dose X-Ray Irradiation in Adipose-Derived Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20236075 ◽

2019 ◽

Vol 20 (23) ◽

pp. 6075 ◽

Cited By ~ 2

Author(s):

Annemarie Schröder ◽

Stephan Kriesen ◽

Guido Hildebrandt ◽

Katrin Manda

Keyword(s):

Stem Cells ◽

Low Dose ◽

Dose Range ◽

Adipose Derived Stem Cells ◽

Long Term Effects ◽

Low Dose Radiation ◽

Term Survival ◽

Cell Therapies ◽

Dose Radiation

(1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno- nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1–2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine.

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Therapeutic Potential of Repeated Intravenous Transplantation of Human Adipose-Derived Stem Cells in Subchronic MPTP-Induced Parkinson’s Disease Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms21218129 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8129

Author(s):

Hyunjun Park ◽

Keun-A Chang

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Neurodegenerative Disease ◽

Neurotrophic Factor ◽

Dopaminergic Neurons ◽

Therapeutic Potential ◽

Adipose Derived Stem Cells ◽

Nigrostriatal Pathway

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which is clinically and pathologically characterized by motor dysfunction and the loss of dopaminergic neurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by researchers; however, no adequate treatment strategy has been established. The results of studies so far have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is a progressively deteriorating neurodegenerative disease that requires long-term treatment, and this has been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal model of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice, hASCs were administered on the tail vein six times at two-week intervals. After the last injection of hASCs, motor function significantly improved. The number of dopaminergic neurons present in the nigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of hASC restored altered dopamine transporter expression and increased neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the striatum. Overall, this study suggests that repeated intravenous transplantation of hASC may exert therapeutic effects on PD by restoring BDNF and GDNF expressions, protecting dopaminergic neurons, and maintaining the nigrostriatal pathway.

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