Background: Anal incontinence is a disabling condition that adversely affects the quality of life of a large number of patients, mainly with anal sphincter lesions. In a previous experimental work, in-vitro expanded bone marrow (BM)-derived mesenchymal stem cells (MSC) were demonstrated to enhance sphincter healing after injury and primary repair in a rat preclinical model. In the present article we investigated whether unexpanded BM mononuclear cells (MNC) may also be effective.
Methods: Thirty-two rats, divided into groups, underwent sphincterotomy and repair (SR) with primary suture of anal sphincters plus intrasphincteric injection of saline (CTR), or of in-vitro expanded MSC, or of minimally manipulated MNC; moreover, the fourth group underwent sham operation. At day 30, histologic, morphometric, in-vitro contractility, and functional analysis were performed.
Results: Treatment with both MSC and MNC improved muscle regeneration and increased contractile function of anal sphincters after SR compared with CTR (p < 0.05). No significant difference was observed between the two BM stem cell types used. GFP-positive cells (MSC and MNC) remained in the proximity of the lesion site up to 30 days post injection.
Conclusions: In the present study we demonstrated in a preclinical model that minimally manipulated BM-MNC were as effective as in-vitro expanded MSC for the recovery of anal sphincter injury followed by primary sphincter repair. These results may serve as a basis for improving clinical applications of stem cell therapy in human anal incontinence treatment.
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http://dx.doi.org/10.1186/s13287-016-0344-x | DOI Listing |
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2100, Denmark.
NMDA receptor ligands have therapeutic potential in neurological and psychiatric disorders. We designed ()-3-(5-thienyl)carboxamido-2-aminopropanoic acid derivatives with nanomolar agonist potencies at NMDA receptor subtypes (GluN12/A-D). These compounds are superagonists at GluN1/2C compared to glycine and partial to full agonists at GluN1/2A and GluN1/2D but display functional antagonism at GluN1/2B due to low agonist efficacy.
View Article and Find Full Text PDFCurr Cancer Drug Targets
January 2025
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Radiotherapy stands as a cornerstone in cancer therapy, with nuclear DNA acknowledged as the principal target molecule for radiation-induced cellular demise or injury. Nonetheless, an expanding body of contemporary research elucidates the significant contri-bution of sphingolipids to radiation-induced cell death, particularly in modulating radiation-induced apoptosis. Radiation can instigate apoptosis through multiple pathways of sphin-golipid metabolism, encompassing the activation of ceramide synthase, acid sphingomyelin-ase, neutral sphingomyelinase, sphingosine-1-phosphate lyase, and sphingosine-1-phosphate phosphatase, and the inhibition of sphingosine kinase-1.
View Article and Find Full Text PDFCarbohydr Polym
March 2025
Key Lab of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. Electronic address:
In an effort to mitigate or reverse the pathological progression of early-stage osteonecrosis of the femoral head (ONFH), this study employed a promising strategy that involves the sustained delivery of osteogenic factors to augment core decompression, facilitated by the use of composite hydrogels. Specifically, a hydrogel was synthesized by blending chitosan, Pluronic F-127, and tripolyphosphate, utilizing both ionic bonding and copolymer micelle cross-linking techniques. This hydrogel demonstrated exceptional biocompatibility, temperature responsiveness, pH-dependent biodegradation, and controlled release properties.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea. Electronic address:
Alzheimer's disease (AD) is characterized as a neurodegenerative disorder that is caused by plaque formation by accumulating β-amyloid (Aβ), leading to neurocognitive function and impaired mental development. Thus, targeting Aβ represents a promising target for the development of therapeutics in AD management. Several functionalized sulfonic acid molecules have been reported, including tramiprosate prodrug, which is currently in clinical trial III and exhibits a good response in mild to moderate AD patients.
View Article and Find Full Text PDFS D Med
December 2024
Sanford Health Reproductive Medicine, Fargo, North Dakota.
Background: The following case report details the genetic evaluation and treatment of a 30-year-old male with a history of asthenoteratospermia and notable abnormalities of the sperm flagella.
Methods: Genetic evaluation was performed via a multi-gene panel of genes associated with primary ciliary dyskinesia and multiple morphological abnormalities of the sperm flagella (MMAF) prior to the couple's in vitro fertilization (IVF) cycle.
Results: Genetic evaluation was performed via a multi-gene panel of genes associated with primary ciliary dyskinesia and multiple morphological abnormalities of the sperm flagella (MMAF) prior to the couple's in vitro fertilization (IVF) cycle.
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