Photobiomodulation Enhances the Angiogenic Effect of Mesenchymal Stem Cells to Mitigate Radiation-Induced Enteropathy

Radiation-induced enteropathy remains a major complication after accidental or therapeutic exposure to ionizing radiation. Recent evidence suggests that intestinal microvascular damage significantly affects the development of radiation enteropathy. Mesenchymal stem cell (MSC) therapy is a promising tool to regenerate various tissues, including skin and intestine. Further, photobiomodulation (PBM), or low-level light therapy, can accelerate wound healing, especially by stimulating angiogenesis, and stem cells are particularly susceptible to PBM. Here, we explored the effect of PBM on the therapeutic potential of MSCs for the management of radiation enteropathy. In vitro, using human umbilical cord blood-derived MSCs, PBM increased proliferation and self-renewal. Intriguingly, the conditioned medium from MSCs treated with PBM attenuated irradiation-induced apoptosis and impaired tube formation in vascular endothelial cells, and these protective effects were associated with the upregulation of several angiogenic factors. In a mouse model of radiation-induced enteropathy, treatment with PBM-preconditioned MSCs alleviated mucosal destruction, improved crypt cell proliferation and epithelial barrier functions, and significantly attenuated the loss of microvascular endothelial cells in the irradiated intestinal mucosa. This treatment also significantly increased angiogenesis in the lamina propria. Together, we suggest that PBM enhances the angiogenic potential of MSCs, leading to improved therapeutic efficacy for the treatment of radiation-induced enteropathy.

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Human cord blood-derived cells attain neuronal and glial features in vitro

Journal of Cell Science ◽

10.1242/jcs.115.10.2131 ◽

2002 ◽

Vol 115 (10) ◽

pp. 2131-2138 ◽

Cited By ~ 1

Author(s):

L. Bużańska ◽

E. K. Machaj ◽

B. Zabłocka ◽

Z. Pojda ◽

K. Domańska-Janik

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Cord Blood ◽

Human Umbilical Cord Blood ◽

Specific Cell ◽

Human Umbilical Cord ◽

Neurofilament Protein ◽

Adhesive Properties ◽

Human Cord Blood

Neural stem cells are clonogenic, self-renewing cells with the potential to differentiate into brain-specific cell lines. Our study demonstrates that a neural-stem-cell-like subpopulation can be selected and expanded in vitro by the use of human umbilical cord blood cells, which are a relatively easily available starting material. Through a combination of antigen-driven magnetic cell sorting and subfractionation according to cell surface adhesive properties, we have isolated a clonogenic fraction devoid of hematopoietic or angiogenetic properties but with relatively high self-renewal potency. The resulting clones express nestin, a neurofilament protein that is one of the most specific markers of multipotent neural stem cells. In the presence of selected growth factors or in the rat brain co-culture system, the progeny of these cells can be oriented towards the three main neural phenotypes: neurons,astroglia and oligodendroglia. The cells show high commitment (about 30% and 40% of the population) to neuronal and astrocytic fate, respectively. Interestingly, upon differentiation, the neural-type precursor cells of cord blood origin also give rise to a relatively high proportion of oligodendrocytes — 11% of the total population of differentiating cells.

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Differentiating characterization of human umbilical cord blood-derived mesenchymal stem cells in vitro

Cell Biology International ◽

10.1016/j.cellbi.2006.02.007 ◽

2006 ◽

Vol 30 (7) ◽

pp. 569-575 ◽

Cited By ~ 52

Author(s):

X KANG ◽

W ZANG ◽

L BAO ◽

D LI ◽

X XU ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord

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Effect of growth differentiation factor-15 secreted by human umbilical cord blood-derived mesenchymal stem cells on amyloid beta levels in in vitro and in vivo models of Alzheimer's disease

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.09.012 ◽

2018 ◽

Vol 504 (4) ◽

pp. 933-940 ◽

Cited By ~ 4

Author(s):

Dong Hyun Kim ◽

Dahm Lee ◽

Hoon Lim ◽

Soo Jin Choi ◽

Wonil Oh ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Amyloid Beta ◽

Umbilical Cord Blood ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord ◽

In Vivo Models ◽

Growth Differentiation Factor 15

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Mouse Mesenchymal Stem Cell-derived Exosomal Mir-466f-3p Reverses Emt Process Through Inhibiting Akt/gsk3β Pathway via C-met in Radiation-induced Lung Injury

10.21203/rs.3.rs-1212153/v1 ◽

2022 ◽

Author(s):

Yi Li ◽

Zhufu Shen ◽

Xiao Jiang ◽

Yuanyuan Wang ◽

Zuozhang Yang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lung Injury ◽

Lung Fibrosis ◽

Luciferase Assay ◽

Mechanistic Study ◽

Protective Effects ◽

Mesenchymal Transition ◽

Radiation Induced

Abstract Background: Radiation-induced lung fibrosis (RILF) is a common complication of thoracic radiotherapy. Alveolar epithelial cells play a crucial role in lung fibrosis via epithelial-mesenchymal transition (EMT). Exosomes derived from mesenchymal stem cells own the beneficial properties to repair and regeneration of damaged tissues, however the underlying mechanisms remain poorly understood. Methods: Mouse mesenchymal stem cells-derived exosomes (mMSCs-Exo) were isolated by differential centrifugation, and their protective effects were assessed in vivo and in vitro , respectively. EMT-associated proteins were measured via western blot assay and/or immunofluorescence staining. The miRNA expression was measured by microarray assay and qPCR. Furthermore, bioinformatics prediction with KEGG analysis, luciferase assay, and rescue experiments were performed to explore the molecular mechanism underlying miR-466f-3p. Results: mMSCs-Exos were efficiently isolated ranging from 90-150 nm with high expression of exosomal markers (CD63, TSG101, and CD9). mMSCs-Exos administration efficiently relieved radiation-induced lung injury with less collagen deposition and lower levels of IL-1β and IL-6. Meanwhile, in vitro results showed mMSCs-Exos treatment obviously reversed EMT process induced by radiation. Among enriched miRNA cargo in exosomes, miR-466f-3p was primarily responsible for the protective effects via inhibition of AKT/GSK3β pathway. Our mechanistic study further demonstrated that c-MET was the direct target of miR-466f-3p, whose restoration partially abrogated mMSCs-Exo-mediated inhibition in both EMT process and AKT/GSK3β signaling activity induced by radiation. Conclusions: Our findings indicated that exosomal miR-466f-3p derived from mMSCs may possess anti-fibrotic properties and prevent radiation-induced EMT through inhibition of AKT/GSK3β via c-MET, providing a promising therapeutic modality for radiation-induced lung fibrosis.

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