Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model.
*Mesenchymal Stem Cell Transplantation; Animals; Conditioned; Culture Media; elastin; external urethral sphincter; Female; Injections; Intraperitoneal; Intravenous; Mesenchymal Stem Cells/metabolism; paracrine action; Parturition; pudendal nerve; Pudendal Nerve/injuries/*physiology; Rats; Sprague-Dawley; Stress/etiology/*prevention & control; Urethra/injuries/*physiology; urinary incontinence; Urinary Incontinence
Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC+VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P \textless 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC+VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC+VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury.
Deng Kangli; Lin Dan Li; Hanzlicek Brett; Balog Brian; Penn Marc S; Kiedrowski Matthew J; Hu Zhiquan; Ye Zhangqun; Zhu Hui; Damaser Margot S
American journal of physiology. Renal physiology
2015
2015-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajprenal.00510.2014" target="_blank" rel="noreferrer noopener">10.1152/ajprenal.00510.2014</a>
MEDIAL CALCIFICATION (WHITLOCKITE) IN THE AORTA
aorta; atheroma; calcium; Cardiovascular System & Cardiology; drinking water; elastin; matrix vesicles; whitlockite
Calcified deposits in the tunica media of the human aorta have been studied in 128 cases by light microscopy and by electron microscopy and analytical methods in selected samples. Although dissolved and not visible in routine histology with alum hematoxylin stains, such calcification can be clearly seen after methylene blue staining in the form of unstained refractile particles of 1-2 mum size. These are found between the elastic laminae chiefly in the inner two-thirds of the media and appear at about age 20. By X-ray diffraction supported by energy dispersive X-ray analysis, they have been identified as whitlockite (Ca,Mg)3(PO4)2. Statistical analysis shows a significant increase in numbers with age and significant differences in severity related to county of origin but no differences between sexes or races and no correlation with deaths related to cardiovascular diseases. Among various substructures of the aortic wall, no unique crystal precursor was identified. Possible etiologic factors and clinicopathologic significance are considered.
Reid J D; Andersen M E
Atherosclerosis
1993
1993-07
Journal Article
<a href="http://doi.org/10.1016/0021-9150(93)90118-e" target="_blank" rel="noreferrer noopener">10.1016/0021-9150(93)90118-e</a>
Rat Mesenchymal Stem Cell Secretome Promotes Elastogenesis And Facilitates Recovery From Simulated Childbirth Injury
Cell Biology; Elastin; Electromyography (EMG); expression; External urethral sphincter (EUS); female; female rats; mice; Paracrine factors; protection; Research & Experimental Medicine; Stress urinary incontinence (SUI); stress urinary-incontinence; stromal cells; tissue; transplantation; transplantation; Urethra; urethral sphincter; vaginal distension
Dissaranan C; Cruz M A; Kiedrowski M; Balog B M; Gill B C; Penn M S; Goldman H B; Damaser M S
Cell Transplantation
2014
2014
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.3727/096368913x670921" target="_blank" rel="noreferrer noopener">10.3727/096368913x670921</a>