scholarly journals Thrombin Preconditioning Enhances Therapeutic Efficacy of Human Wharton’s Jelly–Derived Mesenchymal Stem Cells in Severe Neonatal Hypoxic Ischemic Encephalopathy

2019 ◽  
Vol 20 (10) ◽  
pp. 2477 ◽  
Author(s):  
Young Eun Kim ◽  
Se In Sung ◽  
Yun Sil Chang ◽  
So Yoon Ahn ◽  
Dong Kyung Sung ◽  
...  

We investigated whether thrombin preconditioning of human Wharton’s jelly–derived mesenchymal stem cells (MSCs) improves paracrine potency and thus the therapeutic efficacy of naïve MSCs against severe hypoxic ischemic encephalopathy (HIE). Thrombin preconditioning significantly enhances the neuroprotective anti-oxidative, anti-apoptotic, and anti-cytotoxic effects of naïve MSCs against oxygen–glucose deprivation (OGD) of cortical neurons in vitro. Severe HIE was induced in vivo using unilateral carotid artery ligation and hypoxia for 2 h and confirmed using brain magnetic resonance imaging (MRI) involving >40% of ipsilateral hemisphere at postnatal day (P) 7 in newborn rats. Delayed intraventricular transplantation of 1 × 105 thrombin preconditioned but not naïve MSCs at 24 h after hypothermia significantly enhanced observed anti-inflammatory, anti-astroglial, and anti-apoptotic effects and the ensuing brain infarction; behavioral tests, such as cylinder rearing and negative geotaxis tests, were conducted at P42. In summary, thrombin preconditioning of human Wharton’s jelly-derived MSCs significantly boosted the neuroprotective effects of naïve MSCs against OGD in vitro by enhancing their anti-oxidative, anti-apoptotic, and anti-cytotoxic effects, and significantly attenuated the severe HIE-induced brain infarction and improved behavioral function tests in vivo by maximizing their paracrine anti-inflammatory, anti-astroglial, and anti-apoptotic effects.

Author(s):  
T.R. Sreekumar ◽  
S. Eswari ◽  
K. Vijayarani

Background: The prospect of mesenchymal stem cells (MSCs) as an adult stem cell source for neuronal tissue regeneration via their ability to differentiate into neurons has generated considerable excitement in regenerative cell therapy.Methods: In this study, we isolated ovine Wharton’s jelly derived MSCs and expanded in vitro in adherent culture. After the characterisation of MSCs using specific markers, we analysed the culture morphology of MSCs differentiated into neurons by a two-step chemical-based induction protocols involving a pre-induction step and a direct one step chemical-based induction protocol. Morphological changes after induction were evaluated.Result: In both the methods, after neuronal induction, the cells displayed phenotypic characteristic of neurons and comparatively less cytotoxicity was observed in the direct induction method. This study confirmed the possibility of generating neuron like cells from ovine WJ-MSCs and thereby exploring the potential of MSCs as therapeutic tool for treating neurological disorders in Veterinary Medicine.


2019 ◽  
Vol 20 (18) ◽  
pp. 4351
Author(s):  
Renata Szydlak ◽  
Marcin Majka ◽  
Małgorzata Lekka ◽  
Marta Kot ◽  
Piotr Laidler

Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are multipotent stem cells that can be used in regenerative medicine. However, to reach the high therapeutic efficacy of WJ-MSCs, it is necessary to obtain a large amount of MSCs, which requires their extensive in vitro culturing. Numerous studies have shown that in vitro expansion of MSCs can lead to changes in cell behavior; cells lose their ability to proliferate, differentiate and migrate. One of the important measures of cells’ migration potential is their elasticity, determined by atomic force microscopy (AFM) and quantified by Young’s modulus. This work describes the elasticity of WJ-MSCs during in vitro cultivation. To identify the properties that enable transmigration, the deformability of WJ-MSCs that were able to migrate across the endothelial monolayer or Matrigel was analyzed by AFM. We showed that WJ-MSCs displayed differences in deformability during in vitro cultivation. This phenomenon seems to be strongly correlated with the organization of F-actin and reflects the changes characteristic for stem cell maturation. Furthermore, the results confirm the relationship between the deformability of WJ-MSCs and their migration potential and suggest the use of Young’s modulus as one of the measures of competency of MSCs with respect to their possible use in therapy.


2019 ◽  
Vol 20 (8) ◽  
pp. 1807 ◽  
Author(s):  
Aleksandra Musiał-Wysocka ◽  
Marta Kot ◽  
Maciej Sułkowski ◽  
Bogna Badyra ◽  
Marcin Majka

The properties of mesenchymal stem cells (MSCs), especially their self-renewal and ability to differentiate into different cell lines, are widely discussed. Considering the fact that MSCs isolated from perinatal tissues reveal higher differentiation capacity than most adult MSCs, we examined mesenchymal stem cells isolated from Wharton’s jelly of umbilical cord (WJ-MSCs) in terms of pluripotency markers expression. Our studies showed that WJ-MSCs express some pluripotency markers—such as NANOG, OCT-4, and SSEA-4—but in comparison to iPS cells expression level is significantly lower. The level of expression can be raised under hypoxic conditions. Despite their high proliferation potential and ability to differentiate into different cells type, WJ-MSCs do not form tumors in vivo, the major caveat of iPS cells. Owing to their biological properties, high plasticity, proliferation capacity, and ease of isolation and culture, WJ-MSCs are turning out to be a promising tool of modern regenerative medicine.


2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Peng Huang ◽  
Li Min Lin ◽  
Xiao Ying Wu ◽  
Qiu Ling Tang ◽  
Xue Yong Feng ◽  
...  

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