Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats

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Abstract

The effects of human amniotic fluid stem cell (hAFSC) transplantation on bladder function and molecular changes in spinal cord-injured (SCI) rats were investigated. Four groups were studied: sham and SCI plus phosphate-buffered saline (SCI + PBS), human embryonic kidney 293 (HEK293) cells, and hAFSCs transplantation. In SCI + PBS rat bladders, cystometry showed increased peak voiding pressure, voiding volume, bladder capacity, residual volume, and number of non-voiding contractions, and the total elastin/collagen amount was increased but collagen concentration was decreased at days 7 and 28. Immunoreactivity and mRNA levels of IGF-1, TGF-β1, and β3-adrenoceptor were increased at days 7 and/or 28. M2 immunoreactivity and M3 mRNA levels of muscarinic receptor were increased at day 7. M2 immunoreactivity was increased, but M2/M3 mRNA and M3 immunoreactivity levels were decreased at day 28. Brain derived-neurotrophic factor mRNA was increased, but immunoreactivity was decreased at day 7. HEK293 cell transplantation caused no difference compared to SCI + PBS group. hAFSCs co-localized with neural cell markers and expressed BDNF, TGF-β1, GFAP, and IL-6. The present results showed that SCI bladders released IGF-1 and TGF-β1 to stimulate elastin and collagen for bladder wall remodelling, and hAFSC transplantation improved these changes, which involved the mechanisms of BDNF, muscarinic receptors, and β3-adrenoceptor expression.

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Most cited references 51

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Targeting recovery: priorities of the spinal cord-injured population.

Kim D Anderson (2004)

In the United States alone, there are more than 200,000 individuals living with a chronic spinal cord injury (SCI). Healthcare for these individuals creates a significant economic burden for the country, not to mention the physiological, psychological, and social suffering these people endure everyday. Regaining partial function can lead to greater independence, thereby improving quality of life. To ascertain what functions are most important to the SCI population, in regard to enhancing quality of life, a novel survey was performed in which subjects were asked to rank seven functions in order of importance to their quality of life. The survey was distributed via email, postal mail, the internet, interview, and word of mouth to the SCI community at large. A total of 681 responses were completed. Regaining arm and hand function was most important to quadriplegics, while regaining sexual function was the highest priority for paraplegics. Improving bladder and bowel function was of shared importance to both injury groups. A longitudinal analysis revealed only slight differences between individuals injured 3 years. The majority of participants indicated that exercise was important to functional recovery, yet more than half either did not have access to exercise or did not have access to a trained therapist to oversee that exercise. In order to improve the relevance of research in this area, the concerns of the SCI population must be better known and taken into account. This approach is consistent with and emphasized by the new NIH roadmap to discovery.

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Isolation of amniotic stem cell lines with potential for therapy.

Evan Y Snyder, Gustavo Mostoslavsky, M. Siddiqui … (2007)

Stem cells capable of differentiating to multiple lineages may be valuable for therapy. We report the isolation of human and rodent amniotic fluid-derived stem (AFS) cells that express embryonic and adult stem cell markers. Undifferentiated AFS cells expand extensively without feeders, double in 36 h and are not tumorigenic. Lines maintained for over 250 population doublings retained long telomeres and a normal karyotype. AFS cells are broadly multipotent. Clonal human lines verified by retroviral marking were induced to differentiate into cell types representing each embryonic germ layer, including cells of adipogenic, osteogenic, myogenic, endothelial, neuronal and hepatic lineages. Examples of differentiated cells derived from human AFS cells and displaying specialized functions include neuronal lineage cells secreting the neurotransmitter L-glutamate or expressing G-protein-gated inwardly rectifying potassium channels, hepatic lineage cells producing urea, and osteogenic lineage cells forming tissue-engineered bone.

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A neurologic basis for the overactive bladder.

Henrica de Vet (1997)

The functions of the lower urinary tract (LUT) to store and periodically release urine are dependent on neural circuits in the brain and spinal cord. This paper reviews the central neural control of micturition and how disruption of this control can lead to bladder overactivity and incontinence. Neuroanatomic, electrophysiologic, and pharmacologic techniques have provided information about the neural circuitry and the neurotransmitters involved in the central nervous control of voiding. Experimental models of neural injury, including spinal cord transection, cerebral infarction, and localized brain lesions, have been studied to identify the mechanisms contributing to the neurogenic overactive bladder. Normal storage of urine is dependent on 1) spinal reflex mechanisms that activate sympathetic and somatic pathways to the urethral outlet and 2) tonic inhibitory systems in the brain that suppress the parasympathetic excitatory outflow to the urinary bladder. Voiding is mediated by inhibition of sympathetic-somatic pathways and activation of a spinobulbospinal parasympathetic reflex pathway passing through a micturition center in the rostral pons. Damage to the brain can induce bladder overactivity by reducing suprapontine inhibition. Damage to axonal pathways in the spinal cord leads to the emergence of primitive spinal bladder reflexes triggered by C-fiber bladder afferent neurons. The C-fiber afferent neurotoxin capsaicin, administered intravesically, has been useful in treating certain types of neurogenic bladder overactivity. The central nervous mechanisms controlling the LUT are organized in the brain and spinal cord as simple on-off switching circuits that are under voluntary control. Damage to central inhibitory pathways or sensitization of peripheral afferent terminals in the bladder can unmask primitive voiding reflexes that trigger bladder overactivity.

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Author and article information

Contributors

Tsong-Hai Lee: thlee@adm.cgmh.org.tw

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 22 June 2020

Publication date PMC-release: 22 June 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 10030

Affiliations

[1 ]ISNI 0000 0004 1756 999X, GRID grid.454211.7, Female Urology Section, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, ; Taoyuan, Taiwan

[2 ]GRID grid.145695.a, College of Medicine, Chang Gung University, ; Taoyuan, Taiwan

[3 ]ISNI 0000 0004 1756 999X, GRID grid.454211.7, Division of Obstetrics, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, ; Taoyuan, Taiwan

[4 ]ISNI 0000000121901201, GRID grid.83440.3b, Prenatal Cell and Gene Therapy Group, Institute for Women’s Health, University College London, ; London, UK

[5 ]The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

[6 ]Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

Article

Publisher ID: 67163

DOI: 10.1038/s41598-020-67163-7

PMC ID: 7308393

PubMed ID: 32572272

SO-VID: c687c391-4c92-49d0-a82d-3b9050431a9f

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 1 February 2019

Date accepted : 20 May 2020

Funding

Funded by: FundRef https://doi.org/10.13039/501100005795, Chang Gung Memorial Hospital, Linkou (Linkou Chang Gung Memorial Hospital);

Award ID: CMRPG3G0231

Award ID: CMRPG3H1051

Award ID: CMRPG3H1041

Award Recipient : Ching-Chung Liang Tsong-Hai Lee

Funded by: FundRef https://doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan);

Award ID: MOST 106-2314-B-182A-131

Award ID: MOST 107-2314-B-182A-101

Award ID: MOST 106-2314-B-182A-034 -MY3

Award Recipient : Ching-Chung Liang Tsong-Hai Lee

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ScienceOpen disciplines: Uncategorized

Keywords: spinal cord diseases,bladder

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ScienceOpen disciplines: Uncategorized

Keywords: spinal cord diseases, bladder

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Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats

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UCL: UN SDG 03 Good Health and Well-Being

Most cited references 51

Targeting recovery: priorities of the spinal cord-injured population.

Isolation of amniotic stem cell lines with potential for therapy.

A neurologic basis for the overactive bladder.

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