scholarly journals A Two-Stage Process for Differentiation of Wharton’s Jelly-Derived Mesenchymal Stem Cells into Neuronal-like Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Zaffar Equbal ◽  
Prakash N. Baligar ◽  
Madhulika Srivastava ◽  
Asok Mukhopadhyay
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neurodegenerative Diseases ◽  
Trophic Factors ◽  
Two Stage ◽  
Neuronal Proteins ◽  
Culture Process ◽  
Potential Alternative ◽  
Permanent Cure ◽  
Stage Process

With no permanent cure for neurodegenerative diseases, the symptoms reappear shortly after the withdrawal of medicines. A better treatment outcome can be expected if the damaged neurons are partly replaced by functional neurons and/or they are repaired using trophic factors. In this regard, safe cell therapy has been considered as a potential alternative to conventional treatment. Here, we have described a two-stage culture process to differentiate Wharton Jelly mesenchymal stem cells (WJ-MSCs) into neuronal-like cells in the presence of various cues involved in neurogenesis. The fate of cells at the end of each stage was analyzed at the morphometric, transcriptional, and translational levels. In the first stage of priming, constitutively, wingless-activated WJ-MSCs crossed the lineage boundary in favor of neuroectodermal lineage, identified by the loss of mesenchymal genes with concomitant expression of neuron-specific markers, like SOX1, PAX6, NTRK1, and NEUROD2. Neuronal-like cells formed in the second stage expressed many mature neuronal proteins like Map2, neurofilament, and Tuj1 and possessed axon hillock-like structures. In conclusion, the differentiation of a large number of neuronal-like cells from nontumorigenic and trophic factors secreting WJ-MSCs promises the development of a therapeutic strategy to treat neurodegenerative diseases.

scholarly journals Hypoxic mesenchymal stem cells ameliorate acute kidney ischemia-reperfusion injury via enhancing renal tubular autophagy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei-Cheng Tseng ◽  
Pei-Ying Lee ◽  
Ming-Tsun Tsai ◽  
Fu-Pang Chang ◽  
Nien-Jung Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Recovery ◽  
Trophic Factors ◽  
Left Renal Artery ◽  
Renal Tubular Cells ◽  
Cell Based Therapy ◽  
Renal Tubular

Abstract Background Acute kidney injury (AKI) is an emerging global healthcare issue without effective therapy yet. Autophagy recycles damaged organelles and helps maintain tissue homeostasis in acute renal ischemia-reperfusion (I/R) injury. Hypoxic mesenchymal stem cells (HMSCs) represent an innovative cell-based therapy in AKI. Moreover, the conditioned medium of HMSCs (HMSC-CM) rich in beneficial trophic factors may serve as a cell-free alternative therapy. Nonetheless, whether HMSCs or HMSC-CM mitigate renal I/R injury via modulating tubular autophagy remains unclear. Methods Renal I/R injury was induced by clamping of the left renal artery with right nephrectomy in male Sprague-Dawley rats. The rats were injected with either PBS, HMSCs, or HMSC-CM immediately after the surgery and sacrificed 48 h later. Renal tubular NRK-52E cells subjected to hypoxia-reoxygenation (H/R) injury were co-cultured with HMSCs or treated with HMSC-CM to assess the regulatory effects of HSMCs on tubular autophagy and apoptosis. The association of tubular autophagy gene expression and renal recovery was also investigated in patients with ischemic AKI. Result HMSCs had a superior anti-oxidative effect in I/R-injured rat kidneys as compared to normoxia-cultured mesenchymal stem cells. HMSCs further attenuated renal macrophage infiltration and inflammation, reduced tubular apoptosis, enhanced tubular proliferation, and improved kidney function decline in rats with renal I/R injury. Moreover, HMSCs suppressed superoxide formation, reduced DNA damage and lipid peroxidation, and increased anti-oxidants expression in renal tubular epithelial cells during I/R injury. Co-culture of HMSCs with H/R-injured NRK-52E cells also lessened tubular cell death. Mechanistically, HMSCs downregulated the expression of pro-inflammatory interleukin-1β, proapoptotic Bax, and caspase 3. Notably, HMSCs also upregulated the expression of autophagy-related LC3B, Atg5 and Beclin 1 in renal tubular cells both in vivo and in vitro. Addition of 3-methyladenine suppressed the activity of autophagy and abrogated the renoprotective effects of HMSCs. The renoprotective effect of tubular autophagy was further validated in patients with ischemic AKI. AKI patients with higher renal LC3B expression were associated with better renal recovery. Conclusion The present study describes that the enhancing effect of MSCs, and especially of HMCSs, on tissue autophagy can be applied to suppress renal tubular apoptosis and attenuate renal impairment during renal I/R injury in the rat. Our findings provide further mechanistic support to HMSCs therapy and its investigation in clinical trials of ischemic AKI.

scholarly journals Induction of Neurotrophin Expression via Human Adult Mesenchymal Stem Cells: Implication for Cell Therapy in Neurodegenerative Diseases

2007 ◽  
Vol 16 (1) ◽  
pp. 41-55 ◽  
Author(s):  
Federica Pisati ◽  
Patrizia Bossolasco ◽  
Mirella Meregalli ◽  
Lidia Cova ◽  
Marzia Belicchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Neurodegenerative Diseases ◽  
Human Adult ◽  
Adult Mesenchymal Stem Cells

scholarly journals Serum-mediated Activation of Bone Marrow–derived Mesenchymal Stem Cells in Ischemic Stroke Patients

2018 ◽  
Vol 27 (3) ◽  
pp. 485-500 ◽  
Author(s):  
Gyeong Joon Moon ◽  
Yeon Hee Cho ◽  
Dong Hee Kim ◽  
Ji Hee Sung ◽  
Jeong Pyo Son ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Critical Role ◽  
Trophic Factors ◽  
Human Mscs ◽  
Stroke Patients ◽  
Serum Factors ◽  
Control Serum

Stroke induces complex and dynamic, local and systemic changes including inflammatory reactions, immune responses, and repair and recovery processes. Mesenchymal stem cells (MSCs) have been shown to enhance neurological recovery after stroke. We hypothesized that serum factors play a critical role in the activation of bone marrow (BM) MSCs after stroke such as by increasing proliferation, paracrine effects, and rejuvenation. Human MSCs (hMSCs) were grown in fetal bovine serum (FBS), normal healthy control serum (NS), or stroke patient serum (SS). MSCs cultured in growth medium with 10% SS or NS exhibited higher proliferation indices than those cultured with FBS ( P < 0.01). FBS-, NS-, and SS-hMSCs showed differences in the expression of trophic factors; vascular endothelial growth factor, glial cell–derived neurotrophic factor, and fibroblast growth factor were densely expressed in samples cultured with SS ( P < 0.01). In addition, SS-MSCs revealed different cell cycle– or aging-associated messenger RNA expression in a later passage, and β-galactosidase staining showed the senescence of MSCs observed during culture expansion was lower in MSCs cultured with SS than those cultured with NS or FBS ( P < 0.01). Several proteins related to the activity of receptors, growth factors, and cytokines were more prevalent in the serum of stroke patients than in that of normal subjects. Neurogenesis and angiogenesis were markedly increased in rats that had received SS-MSCs ( P < 0.05), and these rats showed significant behavioral improvements ( P < 0.01). Our results indicate that stroke induces a process of recovery via the activation of MSCs. Culture methods for MSCs using SS obtained during the acute phase of a stroke could constitute a novel MSC activation method that is feasible and efficient for the neurorestoration of stroke.

scholarly journals Human Periapical Cyst-Derived Stem Cells Can Be A Smart “Lab-on-A-Cell” to Investigate Neurodegenerative Diseases and the Related Alteration of the Exosomes’ Content

2019 ◽  
Vol 9 (12) ◽  
pp. 358 ◽  
Author(s):  
Tatullo ◽  
Codispoti ◽  
Spagnuolo ◽  
Zavan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Circadian Rhythm ◽  
Neurodegenerative Diseases ◽  
Clock Genes ◽  
Experimental Studies ◽  
Cell Aging ◽  
A Cell ◽  
Periapical Cyst

Promising researches have demonstrated that the alteration of biological rhythms may be consistently linked to neurodegenerative pathologies. Parkinson’s disease (PD) has a multifactorial pathogenesis, involving both genetic and environmental and/or molecular co-factors. Generally, heterogeneous alterations in circadian rhythm (CR) are a typical finding in degenerative processes, such as cell aging and death. Although numerous genetic phenotypes have been discovered in the most common forms of PD, it seems that severe deficiencies in synaptic transmission and high vesicular recycling are frequently found in PD patients. Neuron-to-neuron interactions are often ensured by exosomes, a specific type of extracellular vesicle (EV). Neuron-derived exosomes may carry several active compounds, including miRNAs: Several studies have found that circulating miRNAs are closely associated with an atypical oscillation of circadian rhythm genes, and they are also involved in the regulation of clock genes, in animal models. In this context, a careful analysis of neural-differentiated Mesenchymal Stem Cells (MSCs) and the molecular and genetic characterization of their exosome content, both in healthy cells and in PD-induced cells, could be a strategic field of investigation for early diagnosis and better treatment of PD and similar neurodegenerative pathologies. A novel MSC population, called human periapical cyst–mesenchymal stem cells (hPCy–MSCs), has demonstrated that it naively expresswa the main neuronal markers, and may differentiate towards functional neurons. Therefore, hPCy–MSCs can be considered of particular interest for testing of in vitro strategies to treat neurological diseases. On the other hand, the limitations of using stem cells is an issue that leads researchers to perform experimental studies on the exosomes released by MCSs. Human periapical cyst-derived mesenkymal stem cells can be a smart “lab-on-a-cell” to investigate neurodegenerative diseases and the related exosomes’ content alteration.

scholarly journals Mesenchymal stem cells in neurodegenerative diseases: Opinion review on ethical dilemmas

2020 ◽  
Vol 12 (3) ◽  
pp. 168-177
Author(s):  
Matteo Scopetti ◽  
Alessandro Santurro ◽  
Vittorio Gatto ◽  
Raffaele La Russa ◽  
Federico Manetti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neurodegenerative Diseases ◽  
Ethical Dilemmas

scholarly journals Human Acellular Amniotic Matrix with Previously Seeded Umbilical Cord Mesenchymal Stem Cells Restores Endometrial Function in a Rat Model of Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Shan Wang ◽  
Cheng Shi ◽  
Xiaohui Cai ◽  
Yanbin Wang ◽  
Xi Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Endometrial Thickness ◽  
Inflammatory Factors ◽  
Matrix Quality ◽  
Endometrial Injury ◽  
Mmp9 Expression ◽  
Injury Group ◽  
Potential Alternative

Background. Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Stem cell transplantation offers a potential alternative for some cases of severe Asherman’s syndrome that cannot be treated with surgery or hormonal therapy. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. However, there is no report on the effects of UCMSCs previously seeded on human acellular amniotic matrix (AAM) on endometrial injury. Methods. Absolute ethanol was injected into rat uteri to damage the endometrium. UCMSCs previously seeded on AAM were surgically transplanted. Using a variety of methods, the treatment response was assessed by endometrial thickness, endometrial biomarker expression, endometrial receptivity, cell proliferation, and inflammatory factors. Results. Endometrial thickness was markedly improved after UCMSC-AAM transplantation. The expression of endometrial biomarkers, namely, vimentin, cytokeratin, and integrin β3, in treated rats increased compared with untreated rats. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. Moreover, in the AAM group, the MMP9 expression increased. The expression of proinflammatory factors (IL-2, TNFα, and IFN-γ) in the UCMSC-AAM group decreased compared with the untreated group, whereas the expression of anti-inflammatory factors (IL-4, IL-10) increased significantly. Conclusions. UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The successful preparation of lyophilized AAM provides the possibility of secondary infectious disease screening and amniotic matrix quality detection, followed by retrospective analysis. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium.

scholarly journals Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wioletta Lech ◽  
Anna Sarnowska ◽  
Zuzanna Kuczynska ◽  
Filip Dabrowski ◽  
Anna Figiel-Dabrowska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Neuroprotective Effect ◽  
Hippocampal Slices ◽  
Wharton’S Jelly ◽  
Trophic Factors ◽  
Differentiation Markers ◽  
Wharton's Jelly

Abstract Tuning stem cells microenvironment in vitro may influence their regenerative properties. In this study Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) were encapsulated in 3D hydrogels derived from human fibrin (FB) or platelet lysate (PL) and the oxygen level was adjusted to physiological normoxia (5% O2). The influence of the type of the scaffold and physiological normoxia conditions was tested on the WJ-MSCs' survivability, proliferation, migratory potential, the level of expression of selected trophic factors, cytokines, and neural markers. Encapsulated WJ-MSCs revealed high survivability, stable proliferation rate, and ability to migrate out of the hydrogel and the up-regulated expression of all tested factors, as well as the increased expression of neural differentiation markers. Physiological normoxia stimulated proliferation of encapsulated WJ-MSCs and significantly enhanced their neuronal, but not glial, differentiation. Ex vivo studies with indirect co-culture of organotypic hippocampal slices and cell-hydrogel bio-constructs revealed strong neuroprotective effect of WJ-MSCs against neuronal death in the CA1 region of the rat hippocampus. This effect was potentiated further by FB scaffolds under 5% O2 conditions. Our results indicating significant effect of oxygen and 3D cytoarchitecture suggest the urgent need for further optimization of the microenvironmental conditions to improve therapeutical competence of the WJ-MSCs population.

Mesenchymal stem cells combined with albendazole as a novel therapeutic approach for experimental neurotoxocariasis

Parasitology ◽  
2020 ◽  
Vol 147 (7) ◽  
pp. 799-809
Author(s):  
E. V. N. Beshay ◽  
S. A. El-Refai ◽  
G. S. Sadek ◽  
A. A. Elbadry ◽  
F. H. Shalan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neurodegenerative Diseases ◽  
Therapeutic Approach ◽  
Toxocara Canis ◽  
Brain Inflammation ◽  
Therapeutic Effects ◽  
Tissue Damages ◽  
Brain Insults ◽  
Novel Therapeutic

AbstractNeurotoxocariasis (NT) is a serious condition that has been linked to reduced cognitive function, behavioural alterations and neurodegenerative diseases. Unfortunately, the available drugs to treat toxocariasis are limited with unsatisfactory results, because of the initiation of treatment at late chronic stages after the occurrence of tissue damage and scars. Therefore, searching for a new therapy for this important disease is an urgent necessity. In this context, cytotherapy is a novel therapeutic approach for the treatment of many diseases and tissue damages through the introduction of new cells into the damaged sites. They exert therapeutic effects by their capability of renewal, differentiation into specialized cells, and being powerful immunomodulators. The most popular cell type utilized in cytotherapy is the mesenchymal stem cells (MSCs) type. In the current study, the efficacy of MSCs alone or combined with albendazole was evaluated against chronic brain insults induced by Toxocara canis infection in an experimental mouse model. Interestingly, MSCs combined with albendazole demonstrated a healing effect on brain inflammation, gliosis, apoptosis and significantly reduced brain damage biomarkers (S100B and GFAP) and T. canis DNA. Thus, MSCs would be protective against the development of subsequent neurodegenerative diseases with chronic NT.

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