Long-Term Tracking of Segmental Bone Healing Mediated by Genetically Engineered Adipose-Derived Stem Cells: Focuses on Bone Remodeling and Potential Side Effects

(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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Long-Term Quantitative Biodistribution and Side Effects of Human Mesenchymal Stem Cells (hMSCs) Engraftment in NOD/SCID Mice following Irradiation

Stem Cells International ◽

10.1155/2014/939275 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Sabine François ◽

Benoit Usunier ◽

Luc Douay ◽

Marc Benderitter ◽

Alain Chapel

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Side Effects ◽

Total Body Irradiation ◽

Human Mesenchymal Stem Cells ◽

Scid Mice ◽

Human Mscs ◽

Long Term Treatment ◽

Total Body

There is little information on the fate of infused mesenchymal stem cells (MSCs) and long-term side effects after irradiation exposure. We addressed these questions using human MSCs (hMSCs) intravenously infused to nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice submitted to total body irradiation (TBI) or local irradiation (abdominal or leg irradiation). The animals were sacrificed 3 to 120 days after irradiation and the quantitative and spatial distribution of hMSCs were studied by polymerase chain reaction (PCR). Following their infusion into nonirradiated animals, hMSCs homed to various tissues. Engraftment depended on the dose of irradiation and the area exposed. Total body irradiation induced an increased hMSC engraftment level compared to nonirradiated mice, while local irradiations increased hMSC engraftment locally in the area of irradiation. Long-term engraftment of systemically administered hMSCs in NOD/SCID mice increased significantly in response to tissue injuries produced by local or total body irradiation until 2 weeks then slowly decreased depending on organs and the configuration of irradiation. In all cases, no tissue abnormality or abnormal hMSCs proliferation was observed at 120 days after irradiation. This work supports the safe and efficient use of MSCs by injection as an alternative approach in the short- and long-term treatment of severe complications after radiotherapy for patients refractory to conventional treatments.

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BONE CELLS UNDER MICROGRAVITY

Journal of Mechanics in Medicine and Biology ◽

10.1142/s021951941340006x ◽

2013 ◽

Vol 13 (05) ◽

pp. 1340006 ◽

Cited By ~ 7

Author(s):

PENG SHANG ◽

JIAN ZHANG ◽

AIRONG QIAN ◽

JINGBAO LI ◽

RUI MENG ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Loss ◽

Bone Remodeling ◽

Bone Cells ◽

Microgravity Environment ◽

Human Beings ◽

Bone Mesenchymal Stem Cells ◽

Skeleton Structure

Weightlessness environment (also microgravity) during the exploration of space is the major condition which must be faced by astronauts. One of the most serious adverse effects on astronauts is the weightlessness-induced bone loss due to the unbalanced bone remodeling. Bone remodeling of human beings has evolved during billions of years to make bone tissue adapt to the gravitational field of Earth (1g) and maintain skeleton structure to meet mechanical loading on Earth. However, under weightlessness environment the skeleton system no longer functions against the pull of gravity, so there is no necessity to keep bone strong enough to support the body's weight. Therefore, the balance of bone remodeling is disrupted and bone loss occurs, which is extremely deleterious to an astronaut's health during long-term spaceflight. Bone remodeling is mainly orchestrated by bone mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. Here, we review how these bone cells respond to microgravity environment.

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